Uncertainty Quantification in Machine Learning for Engineering Design and Health Prognostics: A Tutorial

On top of machine learning models, uncertainty quantification (UQ) functions as an essential layer of safety assurance that could lead to more principled decision making by enabling sound risk assessment and management. The safety and reliability improvement of ML models empowered by UQ has the potential to significantly facilitate the broad adoption of ML solutions in high-stakes decision settings, such as healthcare, manufacturing, and aviation, to name a few. In this tutorial, we aim to provide a holistic lens on emerging UQ methods for ML models with a particular focus on neural networks and the applications of these UQ methods in tackling engineering design as well as prognostics and health management problems. Toward this goal, we start with a comprehensive classification of uncertainty types, sources, and causes pertaining to UQ of ML models. Next, we provide a tutorial-style description of several state-of-the-art UQ methods: Gaussian process regression, Bayesian neural network, neural network ensemble, and deterministic UQ methods focusing on spectral-normalized neural Gaussian process. Established upon the mathematical formulations, we subsequently examine the soundness of these UQ methods quantitatively and qualitatively (by a toy regression example) to examine their strengths and shortcomings from different dimensions. Then, we review quantitative metrics commonly used to assess the quality of predictive uncertainty in classification and regression problems. Afterward, we discuss the increasingly important role of UQ of ML models in solving challenging problems in engineering design and health prognostics. Two case studies with source codes available on GitHub are used to demonstrate these UQ methods and compare their performance in the life prediction of lithium-ion batteries at the early stage and the remaining useful life prediction of turbofan engines

Gap Anisotropy in Iron-Based Superconductors: A Point-Contact Andreev Reflection Study of BaFe2−x_{2-x}Nix_{x}As2_2 Single Crystals

We report a systematic investigation on c-axis point-contact Andreev reflection (PCAR) in BaFe$_{2-x}$Ni$_x$As$_2$ superconducting single crystals from underdoped to overdoped regions (0.075 $\leq x\leq 0.15$). At optimal doping ($x=0.1$) the PCAR spectrum feature the structures of two superconducting gap and electron-boson coupling mode. In the $s\pm$ scenario, quantitative analysis using a generalized Blonder-Tinkham-Klapwijk (BTK) formalism with two gaps: one isotropic and another angle dependent, suggest a nodeless state in strong-coupling limit with gap minima on the Fermi surfaces. Upon crossing above the optimal doping ($x > 0.1$), the PCAR spectrum show an in-gap sharp narrow peak at low bias, in contrast to the case of underdoped samples ($x < 0.1$), signaling the onset of deepened gap minima or nodes in the superconducting gap. This result provides evidence of the modulation of the gap amplitude with doping concentration, consistent with the calculations for the orbital dependent pair interaction mediated by the antiferromagnetic spin fluctuations.Comment: 5 pages, 4 figure

Reversibly tuning the insulating and superconducting state in KxFe2-ySe2 crystals by post-annealing

Since the discovery of superconductivity at 26 K in oxy-pnictide LaFeAsO1-xFx, enormous interests have been stimulated in the field of condensed matter physics and material sciences. Among the many kind of structures in the iron pnictide superconductors, FeSe with the PbO structure has received special attention since there is not poisonous pnictogen element in chemical composition and its structure is the simplest one. However, the superconducting transition temperature (Tc) in iron chalcogenide compounds is not enhanced as high as other iron pnictide superconductors under ambient pressure until the superconductivity at above 30 K in potassium intercalated iron selenide KxFe2-ySe2 was discovered. The insulating and the superconducting state are both observed in KxFe2-ySe2 with different stoichiometries and some groups have tuned the system from insulating to superconducting state by varying the ratio of starting materials[10, 11]. The recent data from neutron scattering suggest that the superconductivity may be built upon an ordered state of Fe vacancies as well as the antiferromagnetic state with a very strong ordered magnetic moment 3.4 B. Here we show that the superconductivity can actually be tuned on a single sample directly from an insulating state by post-annealing and fast quenching. Upon waiting for some days at room temperatures, the superconductivity will disappear and the resistivity exhibits an insulating behavior again. The spatial distribution of the compositions of the as-grown sample and the post-annealed-quenched one was analyzed by the Energy Dispersive X-ray Spectrum (EDXS) and found to be very close to each other. Therefore it is tempting to conclude that the superconductivity is achieved when the Fe-vacancies are in a random (disordered) state. Once they arrange in an ordered state by relaxation or slow cooling, the system turns out to be an insulator.Comment: 12 pages,5 figure

Longitudinal changes in the hypothalamic–pituitary–adrenal axis and sympathetic nervous system are related to the prognosis of stroke

Background and purposeThis study sought to improve methods to identify biomarkers in the neuroendocrine system related to stroke progression to improve the accuracy of traditional tools for evaluating stroke prognosis.MethodsSeventy-four stroke patients and 237 healthy controls were prospectively included. We measured urinary epinephrine (E), noradrenaline (NE), dopamine (DA) and cortisol (F) on days 1, 3, and 5 after stroke onset and plasma F, adrenocorticotropic hormone (ACTH), thyrotropin (TSH), prolactin (PRL), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and growth hormone (GH). The correlation between these hormone levels and 90-day prognosis was analyzed, their value in assessing prognosis was compared with lesion volume and National Institutes of Health Stroke Scale (NIHSS) scores using receiver operating characteristic (ROC) curves, and their correlation with conventional clinical variables was assessed.ResultsLevels of F, 24-h urinary free cortisol(UFC), E, NE, DA, and GH on days 1, 3, and 5 were significantly higher in stroke patients than in controls (P &lt; 0.01), while ACTH and TSH decreased, gradually approaching normal within 5 days of onset. Levels of E, NE, F, and 24-h UFC were proportional to severity, and all gradually decreased within 5 days of onset in patients with a good prognosis and gradually increased or remained high in those with a poor prognosis. After adjustment for age, sex, NIHSS, or Glasgow Coma Scale (GCS) score, F &gt; 13.6 μg/dL, ACTH &gt; 22.02 pg/mL and NE &gt; 123.5 μg/ 24 h were identified as risk factors for a poor prognosis 90 days after stroke (P &lt; 0.05). The combination of F, ACTH, NE, white blood cell count (WBC), glucose (Glu), and hemoglobin (Hb) was significantly more accurate than lesion volume (AUC: 0.931 vs. 0.694 P = 0.019) and NIHSS score (AUC: 0.931 vs. 0.746 P = 0.034) in predicting poor prognosis of stroke 1 day after onset. Hormones and traditional clinical variables were correlated to varying degrees, with NE correlating most strongly with 24-h UFC (r = 0.54) and moderately positively with lesion volume (r = 0.40) and NIHSS score (r = 0.45).ConclusionsStroke causes significant time-phased dynamic changes in the hypothalamic–pituitary–adrenal axis and sympathetic nervous system, and plasma F, ACTH, and urinary NE levels can be used to assess stroke severity and prognosis.Chinese clinical trial registryRegistration Number: ChiCTR1900024992. Registration Date: 2019/8/6

Genetic Variations in Plasma Circulating DNA of HBV-Related Hepatocellular Carcinoma Patients Predict Recurrence after Liver Transplantation

BACKGROUND: Recurrence prediction of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients undergoing liver transplantation (LT) present a great challenge because of a lack of biomarkers. Genetic variations play an important role in tumor development and metastasis. METHODS: Oligonucleotide microarrays were used to evaluate the genetic characteristics of tumor DNA in 30 HBV-related HCC patients who were underwent LT. Recurrence-related single-nucleotide polymorphism were selected, and their prognostic value was assessed and validated in two independent cohorts of HCC patients (N = 102 and N = 77), using pretransplant plasma circulating DNA. Prognostic significance was assessed by Kaplan-Meier survival estimates and log-rank tests. Multivariate analyses were performed to evaluate prognosis-related factors. RESULTS: rs894151 and rs12438080 were significantly associated with recurrence (P = .003 and P = .004, respectively). Multivariate analyses demonstrated that the co-index of the 2 SNPs was an independent prognostic factor for recurrence (P = .040). Similar results were obtained in the third cohort (N = 77). Furthermore, for HCC patients (all the 3 cohorts) exceeding Milan criteria, the co-index was a prognostic factor for recurrence and survival (P<.001 and P = .002, respectively). CONCLUSIONS: Our study demonstrated first that genetic variations of rs894151 and rs12438080 in pretransplant plasma circulating DNA are promising prognostic markers for tumor recurrence in HCC patients undergoing LT and identify a subgroup of patients who, despite having HCC exceeding Milan criteria, have a low risk of post-transplant recurrence

Comparing Outcomes with Bone Marrow or Peripheral Blood Stem Cells as Graft Source for Matched Sibling Transplants in Severe Aplastic Anemia across Different Economic Regions

Bone marrow (BM) is the preferred graft source for hematopoietic stem cell transplantation (HSCT) in severe aplastic anemia (SAA) compared to mobilized peripheral blood stem cells (PBSC). We hypothesized that this recommendation may not apply to those regions where patients present later in their disease course, with heavier transfusion load and with higher graft failure rates. Patients with SAA who received HSCT from an HLA-matched sibling donor from 1995 to 2009 and reported to the Center for International Blood and Marrow Transplant Research or the Japan Society for Hematopoietic Cell Transplantation were analyzed. The study population was categorized by gross national income per capita (GNI) and region/countries into four groups. Groups analyzed were high income countries (HIC), which were further divided into US-Canada (N=486) and other HIC (N=1264), upper middle-income (UMIC) (N=482), and combined lower middle, low income countries (LM-LIC) (N=142). In multivariate analysis, overall survival (OS) was highest with BM as graft source in HIC compared to PBSC in all countries or BM in UMIC or LM-LIC (p<0.001). There was no significant difference in OS between BM and PBSC in UMIC (p=0.32) or LM-LIC (p=0.23). In LM-LIC the 28-day neutrophil engraftment was higher with PBSC compared to BM (97% vs. 77%, p<0.001). Chronic GVHD was significantly higher with PBSC in all groups. Whereas BM should definitely be the preferred graft source for HLA-matched sibling HSCT in SAA, PBSC may be an acceptable alternative in countries with limited resources when treating patients at high risk of graft failure and infective complications

Myeloablative vs Reduced-Intensity Conditioning Allogeneic Hematopoietic Cell Transplantation for Chronic Myeloid Leukemia

Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment of chronic myeloid leukemia (CML). Optimal conditioning intensity for allo-HCT for CML in the era of tyrosine kinase inhibitors (TKIs) is unknown. Using the Center for International Blood and Marrow Transplant Research database, we sought to determine whether reduced-intensity/nonmyeloablative conditioning (RIC) allo-HCT and myeloablative conditioning (MAC) result in similar outcomes in CML patients. We evaluated 1395 CML allo-HCT recipients between the ages of 18 and 60 years. The disease status at transplant was divided into the following categories: chronic phase 1, chronic phase 2 or greater, and accelerated phase. Patients in blast phase at transplant and alternative donor transplants were excluded. The primary outcome was overall survival (OS) after allo-HCT. MAC (n = 1204) and RIC allo-HCT recipients (n = 191) from 2007 to 2014 were included. Patient, disease, and transplantation characteristics were similar, with a few exceptions. Multivariable analysis showed no significant difference in OS between MAC and RIC groups. In addition, leukemia-free survival and nonrelapse mortality did not differ significantly between the 2 groups. Compared with MAC, the RIC group had a higher risk of early relapse after allo-HCT (hazard ratio [HR], 1.85; P = .001). The cumulative incidence of chronic graft-versus-host disease (cGVHD) was lower with RIC than with MAC (HR, 0.77; P = .02). RIC provides similar survival and lower cGVHD compared with MAC and therefore may be a reasonable alternative to MAC for CML patients in the TKI era