Discussion on "Bayesian meta-analysis of penetrance for cancer risk" by Thanthirige Lakshika M. Ruberu, Danielle Braun, Giovanni Parmigiani, and Swati Biswas.

We congratulate the authors for the new meta-analysis model that accounts for different outcomes. We discuss the modeling choice and the Bayesian setting, specifically, we point out the connection between the Bayesian hierarchical model and a mixed-effect model formulation to subsequently discuss possible future method extensions.

Maximum spherical mean value filtering for whole-brain QSM.

PURPOSE: To develop a tissue field-filtering algorithm, called maximum spherical mean value (mSMV), for reducing shadow artifacts in QSM of the brain without requiring brain-tissue erosion. THEORY AND METHODS: Residual background field is a major source of shadow artifacts in QSM. The mSMV algorithm filters large field-magnitude values near the border, where the maximum value of the harmonic background field is located. The effectiveness of mSMV for artifact removal was evaluated by comparing existing QSM algorithms in numerical brain simulation as well as using in vivo human data acquired from 11 healthy volunteers and 93 patients. RESULTS: Numerical simulation showed that mSMV reduces shadow artifacts and improves QSM accuracy. Better shadow reduction, as demonstrated by lower QSM variation in the gray matter and higher QSM image quality score, was also observed in healthy subjects and in patients with hemorrhages, stroke, and multiple sclerosis. CONCLUSION: The mSMV algorithm allows QSM maps that are substantially equivalent to those obtained using SMV-filtered dipole inversion without eroding the volume of interest.

Observer design for Takagi-Sugeno fuzzy systems with unmeasured premise variables: Conservatism reduction using line integral Lyapunov function.

In this paper, a non-quadratic Lyapunov function is employed to reduce conservatism in a nonlinear observer designed for a class of continuous-time Takagi-Sugeno fuzzy systems with unmeasurable premise variables. This structure presents greater challenges compared to systems with measured variables. To overcome this issue, we utilize the mean value theorem and the sector nonlinearity transformation to convert the nonlinear error dynamics into a linear parameter-varying system. Moreover, we introduce the line integral Lyapunov function, which based on the integral of the membership functions, in order to ensure the global stability of the fuzzy systems under consideration. The use of this function offers several notable advantages over conventional quadratic forms, including a reduction in conservatism. Additionally, this type of functions constructed in a manner that eliminates the need for generating time derivatives of the membership functions, thereby simplifying calculations and analysis in comparison to other nonquadratic functions. Furthermore, it also enables capturing the system's behavior along a trajectory. The stability conditions are more relaxed and expressed as linear matrix inequalities, which can be solved using a linear programming approach through specialized software tools. To validate the effectiveness of the proposed methodology, we conducted a hardware-in-the-loop test using a flexible joint robot. The obtained results clearly underscore the success of the proposed approach.

Projections of human papillomavirus vaccination and its impact on cervical cancer using the Caputo fractional derivative.

We propose a fractional order model for human papillomavirus (HPV) dynamics, including the effects of vaccination and public health education on developing cervical cancer. First, we discuss the general structure of Caputo fractional derivatives and integrals. Next, we define the fractional HPV model using Caputo derivatives. The model equilibrium quantities, with their stability, are discussed based on the magnitude of the reproduction number. We compute and simulate numerical solutions of the presented fractional model using the Adams-Bashforth-Moulton scheme. Meanwhile, real data sourced from reports from the World Health Organization is used to establish the parameters and compute the basic reproduction number. We present figures of state variables for different fractional orders and the classical integer order. The impacts of vaccination and public health education are discussed through numerical simulations. From the results, we observe that an increase in both vaccination rates and public health education increases the quality of life, and thus, reduces disease burden and suffering in communities. The results also confirm that modeling HPV transmission dynamics using fractional derivatives includes history effects in the model, making the model further insightful and appropriate for studying HPV dynamics.

Adiabatic Amplification of Energy and Magnetic Moment of a Charged Particle after the Magnetic Field Inversion.

We study the evolution of the energy and magnetic moment of a quantum charged particle placed in a homogeneous magnetic field, when this field changes its sign adiabatically. We show that after a single magnetic field passage through zero value, the famous adiabatic invariant ratio of energy to frequency is reestablished again, but with a proportionality coefficient higher than in the initial state. The concrete value of this proportionality coefficient depends on the power index of the frequency dependence on time near zero point. In particular, the adiabatic ratio of the initial ground state (with zero radial and angular quantum numbers) triplicates if the frequency tends to zero linearly as a function of time. If the Larmor frequency attains zero more than once, the adiabatic proportionality coefficient strongly depends on the lengths of the time intervals between zero points, so that the mean energy behavior can be quasi-stochastic after many passages through zero value. The original Born-Fock adiabatic theorem does not work after the frequency passes through zero. However, its generalization is found: the initial Fock state becomes a wide superposition of many instantaneous Fock states, whose weights do not depend on time in the new adiabatic regime.

RbQE: An Efficient Method for Content-Based Medical Image Retrieval Based on Query Expansion.

Systems for retrieving and managing content-based medical images are becoming more important, especially as medical imaging technology advances and the medical image database grows. In addition, these systems can also use medical images to better grasp and gain a deeper understanding of the causes and treatments of different diseases, not just for diagnostic purposes. For achieving all these purposes, there is a critical need for an efficient and accurate content-based medical image retrieval (CBMIR) method. This paper proposes an efficient method (RbQE) for the retrieval of computed tomography (CT) and magnetic resonance (MR) images. RbQE is based on expanding the features of querying and exploiting the pre-trained learning models AlexNet and VGG-19 to extract compact, deep, and high-level features from medical images. There are two searching procedures in RbQE: a rapid search and a final search. In the rapid search, the original query is expanded by retrieving the top-ranked images from each class and is used to reformulate the query by calculating the mean values for deep features of the top-ranked images, resulting in a new query for each class. In the final search, the new query that is most similar to the original query will be used for retrieval from the database. The performance of the proposed method has been compared to state-of-the-art methods on four publicly available standard databases, namely, TCIA-CT, EXACT09-CT, NEMA-CT, and OASIS-MRI. Experimental results show that the proposed method exceeds the compared methods by 0.84%, 4.86%, 1.24%, and 14.34% in average retrieval precision (ARP) for the TCIA-CT, EXACT09-CT, NEMA-CT, and OASIS-MRI databases, respectively.

Location of Early Stage Tumor Detection using Microwave Imaging in the Breast Phantom.

BACKGROUND: Universally, the most predominant cause of female mortality is mainly due to breast cancer. Owing to numerous constraints in the existing imaging technique, researchers are trying out an alternative tool to detect the tumor before going to the miserable stage. METHODS: This article presents a novel method to detect the mean value system for detecting the location of the tumor in different depths by shifting the antenna anywhere in the breast tissue. In addition, an algorithm to reconstruct the breast image, namely Delay-Multiply-and-Sum (DMAS) is followed to identify the tumor implanted in the breast tissue. RESULTS: The analysis shows that the maximum mean value occurs while the antenna moves very near to the tumor while the mean value reduces while the antenna shifts apart from the tumor location. The mean value in different locations is converted into a microwave image. The high intensity in the image exhibits the precise position of the tumor. This technique can identify the location of early-stage tumor of size 3mm. Multiple tumors of sizes 6mm and 7mm can identify at a depth of 12mm and 18mm in the homogeneous breast phantom. DMAS can provide better imaging results in the early stage tumor of size 3mm embedded in the breast phantom. CONCLUSION: Microwave imaging is an efficient technique to differentiate healthy and malignant tissue in the breast. Antenna plays a major role in identifying tumors in the breast in the early stage. Hence a high-performance Ultra Wideband Dielectric Resonator Antenna (DRA-UWB) is used to identify the tumor in the breast. An antenna is sketched in different locations of the breast phantom. On account of the hemispherical structure, the mean value of the reflected signal is high at the center than at the edge. Hence, the difference in mean value is calculated with and without breast phantom for identifying the tumor location. The overall efficiency of this technique can be improved by using a high-performance UWB antenna. The image of the breast is reformed by the DMAS beamforming algorithm.

Region Expansion of Background Field Removal with Local Spherical Harmonics Approximation for Whole-brain Quantitative Susceptibility Mapping.

PURPOSE: Quantitative susceptibility mapping (QSM) is useful for obtaining biological information. To calculate susceptibility distribution, it is necessary to calculate the local field caused by the differences of susceptibility between the tissues. The local field can be obtained by removing a background field from a total field acquired by MR phase image. Conventional approaches based on spherical mean value (SMV) filtering, which are widely used for background field calculations, fail to calculate the background field of the brain surface region corresponding to the radius of the SMV kernel, and consequently cannot calculate the QSM of the brain surface region. Accordingly, a new method calculating the local field by expansively removing the background field is proposed for whole brain QSM. METHODS: The proposed method consists of two steps. First, the background field of the brain surface is calculated from the total field using a locally polynomial approximation of spherical harmonics. Second, the whole brain local field is calculated by SMV filtering with a constraint term of the background field of the brain surface. The parameters of the approximation were optimized to reduce calculation errors through simulations using both a numerical phantom and a measured human brain. Performance of the proposed method with the optimized parameters was quantitatively and visually compared with conventional methods in an experiment of five healthy volunteers. RESULTS: The proposed method showed the accurate local field over the expanded brain region in the simulation studies. It also showed consistent QSM with conventional methods inside of the brain surface and showed clear vein structures on the brain surface. CONCLUSION: The proposed method enables accurate calculation of whole brain QSM without eroding the brain surface region while maintaining same values inside of the brain surface as the conventional methods.

The Magnitude of Crohn's Disease Direct Costs in Health Care Systems (from Different Perspectives): A Systematic Review.

BACKGROUND: The prevalence of inflammatory bowel disease (IBD) has been increasing worldwide, causing high impact on the quality of life of patients and an increasing burden for health care systems. In this systematic review, we reviewed the literature concerning the direct costs of Crohn's disease (CD) for health care systems from different perspectives: regional, economic, and temporal. METHODS: We searched for original real-world studies examining direct medical health care costs in Crohn's disease. The primary outcome measure was the mean value per patient per year (PPY) of total direct health care costs for CD. Secondary outcomes comprised hospitalization, surgery, CD-related medication (including biologics), and biologics mean costs PPY. RESULTS: A total of 19 articles were selected for inclusion in the systematic review. The studies enrolled 179 056 CD patients in the period between 1997 and 2016. The pooled mean total cost PPY was €6295.28 (95% CI, €4660.55-€8503.41). The pooled mean hospitalization cost PPY for CD patients was €2004.83 (95% CI, €1351.68-€2973.59). The major contributors for the total health expenditure were biologics (€5554.58) and medications (€3096.53), followed by hospitalization (€2004.83) and surgery (€1883.67). No differences were found between regional or economic perspectives, as confidence intervals overlapped. However, total costs were significantly higher after 2010. CONCLUSIONS: Our review highlighted the burden of CD for health care systems from different perspectives (regional, economic, and temporal) and analyzed the impact of the change of IBD treatment paradigm on total costs. Reducing the overall burden can depend on the increase of remission rates to further decrease hospitalizations and surgeries.

Results of Determination of Mean Values and Reference Intervals for Some Vitamins / Монголын Анагаах Ухаан

Background@#Vitamins are nutrients essential for human health. They act as coenzymes that help trigger important chemical reactions necessary for energy production. Reference values for vitamins help physicians evaluate the health status of patients and make clinical decisions. The aim of this study was to determine the mean values and reference intervals for some water-soluble vitamins of Mongolian adults.@*Materials and Methods@#Three hundred and forty healthy adults (170 males and 170 females) of 17 to 69 years of age were selected for the study based on CLSI C28-P3 criteria Defining, establishing & Verifying reference interval in the clinical laboratory; Proposed Guidelines. The study was approved by the Resolution No.76 of 2018 of the Medical Ethics Review Committee of the Ministry of Health. Informed consents were taken from the selected individuals. Morning blood samples of the participants were collected under aseptic conditions. Levels of vitamins B₆, B₉, B₁₂ and vitamin C were measured using a high performance liquid chromatography method. The lower- and upper reference limits were defined as the 2.5th and 97.5th percentiles, respectively. The data were analyzed using SPSS and Excel programs.@*Results@#The mean blood level of vitamin C was 11.88 mg/L (95% CI 10.47-13.29) for men and 9.62 mg/L (95% CI 8.11-11.13) for women. The calculated reference interval for males was 1.40-19.40 mg/L and 1.17-18.04 mg/L for females. The mean concentration of vitamin B₁₂ in the blood of males was 938.45 ng/L (95% CI 747.22-1129.68) and that of females was 864.03 ng/L (95% CI 603.81-1124.25). The reference interval for vitamin B₁₂ was 233.03-1597.00 ng/L in men and 132.45-1623.86 ng/L in women. The mean level of vitamin B₉ was 8.47 ng/mL (95% CI 5.64-11.30) for men and 6.91 ng/mL (95% CI 4.89-8.93) for women. The calculated reference interval for this vitamin in males was 1.04-24.74 ng/mL and that in females was 1.04-21.46 ng/mL. As for vitamin B₆, the mean concentration for men was 44.42 ng/mL (95% CI 37.01-51.83) and for women was 34.67 ng/mL (95% CI 29.97-39.39) with the reference intervals of 5.90-79.02 ng/mL for men and 5.27-61.72 ng/mL for women. @*Conclusion@#The reference values for vitamins B₆, B₉, B₁₂ and vitamin C of Mongolian adults do not differ significantly from those observed in other populations. The calculated reference intervals can be used in the practice of health laboratories.

Alternative care providers in rheumatoid arthritis patient care: a queueing and simulation analysis.

Patients diagnosed with rheumatoid arthritis require lifelong monitoring by a rheumatologist. Initiation of the disease-modifying anti-rheumatic drug therapy within twelve weeks of the onset of symptoms is crucial to prevent joint damage and functional disability. We examine the impact of the engagement of alternate care providers (ACP) in alleviating delay due to limited rheumatologist capacity. Using queueing theory and discrete-event simulation, we model rheumatologist-only and rheumatologist-with-ACP system configurations as closed, multi-class queueing networks with class switching.Using summary data from an actual rheumatology clinic for illustration, we analyze various parameter conditions to aid clinic managers and policymakers in decisions concerning capacity allocations and feasible patient panel size that impact timeliness of care and resource utilization.Results not only confirm that a substantial increase in RA patient panel size with an ACP involved in the care of follow-up patients but also demonstrates the boundaries for feasible panel sizes and workload allocation.

Analysis of fitness among Korean adults by the cause-effect relation in lump mean scheme.

BACKGROUND: The aim of this study was to examine whether the fitness of Korean adults can be analyzed by the cause-effect relation using the linearity or Gaussianity in the lump mean scheme (LMS). METHODS: This study analyzed previous results for the sit-up test obtained in the LMS by regression analysis in Sigmaplot 14. The effects of the body mass index (BMI) and new waist-to-height ratio (WHT2R) introduced by the present author on fitness were investigated. RESULTS: The distribution of the sit-up test score with respect to the BMI and WHT2R were interpreted by their Gaussianity and linearity, respectively. This means that the muscular endurance of males is determined by two causes (fat and muscle) when the BMI is a variable and one cause (abdominal fat) when the WHT2R is a variable. CONCLUSIONS: Personal exercise aims were simpler to establish using WHT2R than using BMI. On the other hand, it was recommended for people with a low BMI to increase their fitness using exercises that increase their muscle mass.

Association Between Obesity and Blood Pressure in Common Korean People.

PURPOSE: The aim of this study was to investigate the associations of high blood pressure (BP) and wide pulse pressure (PP) with obesity among common Korean people. MATERIALS AND METHODS: This study analyzed data from the Seventh Korean National Health and Nutrition Examination Survey (2017). The associations of BP with body mass index (BMI) and waist-to-height ratio (WHT2R) were investigated using their lump mean values. RESULTS: The BPs of males and females increased with BMI, the PP of females increased with BMI and then decreased, and the PP of males is nearly independent of BMI. The BPs of males and females increased to their maximum values with WHT2R and then decreased. The PPs of males and females increased with WHT2R. CONCLUSION: BMI can be used as a useful predictor for high BP, and WHT2R can be used as a useful predictor for wide PP.

On Representations of Divergence Measures and Related Quantities in Exponential Families.

Within exponential families, which may consist of multi-parameter and multivariate distributions, a variety of divergence measures, such as the Kullback-Leibler divergence, the Cressie-Read divergence, the Rényi divergence, and the Hellinger metric, can be explicitly expressed in terms of the respective cumulant function and mean value function. Moreover, the same applies to related entropy and affinity measures. We compile representations scattered in the literature and present a unified approach to the derivation in exponential families. As a statistical application, we highlight their use in the construction of confidence regions in a multi-sample setup.

Single-step calculation of susceptibility through multiple orientation sampling.

Quantitative susceptibility mapping (QSM) was developed to estimate the spatial distribution of magnetic susceptibility from MR signal phase acquired using a gradient echo (GRE) sequence. The field-to-susceptibility inversion in QSM is known to be ill-posed and needs numerical stabilization through either regularization or data oversampling. The calculation of susceptibility through the multiple orientation sampling (COSMOS) method uses phase data acquired at three or more head orientations to achieve a well-conditioned field-to-susceptibility inversion and is often considered the gold standard for in vivo QSM. However, the conventional COSMOS approach, here named multistep COSMOS (MSCOSMOS), solves the dipole inversion from the local field derived from raw GRE phase through multiple steps of phase preprocessing. Error propagations between these consecutive phase processing steps can thus affect the final susceptibility quantification. On the other hand, recently proposed single-step QSM (SSQSM) methods aim to solve an integrated inversion from unprocessed or total phase to mitigate such error propagations but have been limited to single orientation QSM. This study therefore aimed to test the feasibility of using single-step COSMOS (SSCOSMOS) to jointly perform background field removal and dipole inversion with multiple orientation sampling, which could serve as a better standard for gauging SSQSM methods. We incorporated multiple spherical mean value (SMV) kernels of various radii with the dipole inversion in SSCOSMOS. QSM reconstructions with SSCOSMOS and MSCOSMOS were compared using both simulations with a numerical head phantom and in vivo human brain data. SSCOSMOS permitted integrated background removal and dipole inversion without the need to adjust any regularization parameters. In addition, with sufficiently large SMV kernels, SSCOSMOS performed consistently better than MSCOSMOS in all the tested error metrics in our simulations, giving better susceptibility quantification and smaller reconstruction error. Consistent tissue susceptibility values were obtained between SSCOSMOS and MSCOSMOS.

Application of Life-Dependent Material Parameters to Fatigue Life Prediction under Multiaxial and Non-Zero Mean Loading.

This study presents the life-dependent material parameters concept as applied to several well-known fatigue models for the purpose of life prediction under multiaxial and non-zero mean loading. The necessity of replacing the fixed material parameters with life-dependent parameters is demonstrated. The aim of the research here is verification of the life-dependent material parameters concept when applied to multiaxial fatigue loading with non-zero mean stress. The verification is performed with new experimental fatigue test results on a 7075-T651 aluminium alloy and S355 steel subjected to multiaxial cyclic bending and torsion loading under stress ratios equal to R = -0.5 and 0.0, respectively. The received results exhibit the significant effect of the non-zero mean value of shear stress on the fatigue life of S355 steel. The prediction of fatigue life was improved when using the life-dependent material parameters compared to the fixed material parameters.

Low CSF/serum ratio of free T4 is associated with decreased quality of life in mild hypothyroidism - A pilot study.

BACKGROUND & OBJECTIVE: Patients with mild hypothyroidism often are depressed and have impaired quality of life despite serum free-T4 and T3 within reference values. Therefore, we investigated whether their symptoms were dependent on the concentrations of free -T4 and T3 in the circulation and cerebrospinal fluid (CSF). METHODS: Twenty-five newly diagnosed, untreated hypothyroid subjects and as many age- and sex-matched healthy controls were investigated. Blood and CSF sampling was performed in the morning after an overnight fast. Quality of life (QoL) was assessed by a Likert scale. In the hypothyroid subjects, the MADRS rating scale was also used to evaluate symptoms of depression. Furthermore, the results obtained by the questionnaires were related to serum and CSF levels of free- T4 and T3 as well as the ratios between them in CSF and in serum. RESULTS: Self-reported health was considerably lower in hypothyroid subjects. MADRS was considerably higher than the normal range for healthy individuals. Low CSF/serum free-T4 ratio was correlated with an increased depressed state according to MADRS (p < 0.01), and in addition, CSF/serum free-T4 ratio correlated positively with the self-reported general health Likert scale (p < 0.05). Concentrations of TSH, or free-T3 in serum or CSF, were not associated with an increased depressed state or self-reported general health. CONCLUSIONS: Low CSF/serum ratio of free-T4 was correlated with impaired general health and mood, in contrast to serum measurements not showing any correlations. These findings might partly explain why some patients with hypothyroidism suffer from mental symptoms, despite adequate serum levels of free-T4. However, the findings need to be confirmed in further and larger studies.

Investigating the equivalent performance of biparametric compared to multiparametric MRI in detection of clinically significant prostate cancer.

PURPOSE: PIRADS v2 stipulates that dynamic contrast-enhanced (DCE) imaging be used to categorize diffusion-weighted-imaging (DWI) score 3 (DWI 3) peripheral zone (PZ) lesions as PIRADS score 3 (PIRADS 3; DCE -) or PIRADS 4 (DCE +). It's controversial for the value of DCE in improving clinically significant prostate cancer (csPCa) detection. We aimed to figure out whether DCE improves csPCa detection and explore new available measures to improve csPCa detection. PATIENTS AND METHODS: We retrospectively enrolled 375 patients who underwent mp MRI before MRI/ultrasound (US) fusion-targeted biopsy (TB) with transperineal systematic biopsy (SB). All lesions were classified as DWI 3/DCE -, DWI 3/DCE +, DWI 4/PIRADS 4 lesions. Detection rates of csPCa for each lesion group were analyzed. The diagnostic performance of each approach was analyzed by receiver operating characteristics (ROC) analysis and decision curve analysis. RESULTS: Totally, 109 DWI 3 or DWI 4 single lesions in PZ were analyzed (n = 109). The rates of csPCa detection for Group A, Group B, Group C is 10.3%, 13.9%, 55.9%, respectively (A vs. B, p = 0.625; B vs. C, p < 0.001). ROC analysis and decision curve analysis showed the method of combining Age, PSA Density (PSAD) and the mean apparent diffusion coefficient value (ADCmean) outperforms individual approaches for csPCa detection. CONCLUSION: For DWI 3 lesions in PZ, DCE sequence has not additional value for improving detection of csPCa. The integration of clinical characteristics and bpMRI parameter improves the detection of csPCa.

The non-compartmental steady-state volume of distribution revisited.

The lack in the literature of a simple, yet general and complete derivation of the widely used equation for non-compartmental calculation of steady-state volume of distribution is pointed out. It is demonstrated that the most frequently cited references contain an overly simplified explanation. The logical gap consists in doubly defining the same quantities without a proof the definitions are equivalent. Two alternative solutions are proposed: analytical derivation and hydrodynamic analogy. It is shown, that the problem can be analyzed in a purely macroscopic framework by utilizing the integral mean value of the function, without the need to resort to statistical distributions.

Computational method for multiphase flow characterization in the gas refinery.

This paper presents a new computational method for the decentralized multiphase flow measurement based on the interconnections between the two subsystems to precisely estimate the states of the multiphase flow at the gas refinery. The states of the condensate and gas sub-systems were separately estimated using the Differential Mean Value Theorem by considering the relationship between two subsystems, designing an observer and converting the conditions to linear matrix inequality. To check the stability and performance of the system against the changes, the Lyapunov theory has been used. The states behavior investigated with and without disturbance in the system output and dynamics. Additionally, the Unscented Kalman Filter based on the simplified drift flux model was used to estimate the states. It is found that both observers are capable to identify the states with some differences in performance and drift flux model is sufficient for estimation of parameters and states.