On a Reconstruction of a Solely Time-Dependent Source in a Time-Fractional Diffusion Equation with Non-smooth Solutions

An inverse source problem for a non-automonous time fractional diffusion equation of order (0 < β< 1) is considered in a bounded Lipschitz domain in Rd. The missing solely time-dependent source is recovered from an additional integral measurement. The existence, uniqueness and regularity of a weak solution is studied. We design two numerical algorithms based on Rothe’s method over uniform and graded grids, derive a priori estimates and prove convergence of iterates towards the exact solution. An essential feature of the fractional subdiffusion problem is that the solution lacks the smoothness near the initial time, although it would be smooth away from t= 0. Rothe’s method on a uniform grid addresses the existence of a such a solution (non-smooth with tγ term where 1 > γ> β) under low regularity assumptions, whilst Rothe’s method over graded grids has the advantage to cope better with the behaviour at t= 0 (also here tβ is included in the class of admissible solutions) for the considered problems. The theoretical obtained results are supported by numerical experiments and stay valid in case of smooth solutions to the problem. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.106016/12P2919N; Universiteit Gent; Russian Science Foundation, RSF: 22-21-00075A. S. Hendy wishes to acknowledge the support of the RSF grant, project 22-21-00075. K. Van Bockstal is supported by a postdoctoral fellowship of the Research Foundation - Flanders (106016/12P2919N).The authors are grateful to the handling editor and the anonymous referees for their constructive feedback and helpful suggestions, which highly improved the paper. The authors would also like to thank Professor Vladimir G. Pimenov of Ural Federal University and Professor Mari?n Slodi?ka of Ghent University, for their generosity and guidance, which has always been so valuable to them

Granular dot-like staining with MLH1 immunohistochemistry is a clone-dependent artefact

Immunohistochemistry (IHC) for DNA mismatch repair proteins MLH1, PMS2, MSH2, and MSH6 is used for microsatellite instability (MSI) screening in colorectal carcinoma (CRC) and endometrial carcinoma (EC). Loss of PMS2, with retained MLH1 staining occurs in germline mutations of PMS2 gene, and is an indication for genetic testing. We report a pitfall of immunohistochemical interpretation in an EC, initially regarded as MLH1-positive and PMS2-negative. Review of the MLH1-IHC (M1-clone) revealed a granular, dot-like, nuclear staining. On repeating the MLH1-IHC with a different clone (ES05-clone), complete negativity was noted, and on molecular testing, MLH1 promotor methylation was detected. The dot-like pattern was therefore adjudged a clone-dependent artefact. On reviewing the archived MLH1-IHC slides, we observed the same dot-like pattern in two CRCs; in both cases the M1-clone had been used. Awareness of this artefact may prevent reporting errors, and unnecessary referrals for germline mutation testing

RIGHT-FIELD SUBMILLIMETER MAGNETO-SPECTROSCOPY ON Hg(Fe)Se

Magnetooptical phenomena in the zero-gap semimagnetic semiconductor Hg(Fe)Se are studied by various techniques in pulsed magnetic fields up to 150 Τ. Microscopical parameters are estimated in combination with results obtained from transport and magnetization measurements

Clinical and economic impact of HeartLogic (TM) compared with standard care in heart failure patients

Aims The implantable cardiac defibrillator/cardiac resynchronization therapy with defibrillator-based HeartLogic (TM) algorithm has recently been developed for early detection of impending decompensation in heart failure (HF) patients; but whether this novel algorithm can reduce HF hospitalizations has not been evaluated. We investigated if activation of the HeartLogic algorithm reduces the number of hospital admissions for decompensated HF in a 1 year post-activation period as compared with a 1 year pre-activation period.Methods and results Heart failure patients with an implantable cardiac defibrillator/cardiac resynchronization therapy with defibrillator with the ability to activate HeartLogic and willingness to have remote device monitoring were included in this multicentre non-blinded single-arm trial with historical comparison. After a HeartLogic alert, the presence of HF symptoms and signs was evaluated. If there were two or more symptoms and signs apart from the HeartLogic alert, lifestyle advices were given and/or medication was adjusted. After activation of the algorithm, patients were followed for 1 year. HF events occurring in the 1 year prior to activation and in the 1 year after activation were compared. Of the 74 eligible patients (67.2 +/- 10.3 years, 84% male), 68 patients completed the 1 year follow-up period. The total number of HF hospitalizations reduced from 27 in the pre-activation period to 7 in the post-activation period (P = 0.003). The number of patients hospitalized for HF declined from 21 to 7 (P = 0.005), and the hospitalization length of stay diminished from average 16 to 7 days (P = 0.079). Subgroup analysis showed similar results (P = 0.888) for patients receiving cardiac resynchronization therapy during the pre-activation period or not receiving cardiac resynchronization therapy, meaning that the effect of hospitalizations cannot solely be attributed to reverse remodelling. Subanalysis of a single-centre Belgian subpopulation showed important reductions in overall health economic costs (P = 0.025).Conclusion Activation of the HeartLogic algorithm enables remote monitoring of HF patients, coincides with a significant reduction in hospitalizations for decompensated HF, and results in health economic benefits.Cardiolog

EXclusion of non-Involved uterus from the Target Volume (EXIT-trial): An individualized treatment for locally advanced cervical cancer using modern radiotherapy and imaging techniques

Background: Definitive chemoradiotherapy is standard of care in locally advanced cervical cancer (LACC). Both toxicity and local relapse remain major concerns in this treatment. We hypothesize that a magnetic resonance imaging (MRI) based redefining of the radiotherapeutic target volume will lead to a reduction of acute and late toxicity. In our center, chemoradiotherapy followed by hysterectomy was implemented successfully in the past. This enables us to assess the safety of reducing the target volume but also to explore the biological effects of chemoradiation on the resected hysterectomy specimen. Methods: The EXIT-trial is a phase II, single arm study aimed at LACC patients. This study evaluates whether a MRI-based exclusion of the non-tumor-bearing parts of the uterus out of the target volume results in absence of tumor in the non-high doses irradiated part of the uterus in the hysterectomy specimen. Secondary endpoints include a dosimetric comparison of dose on normal tissue when comparing study treatment plans compared to treatment of the whole uterus at high doses; acute and chronic toxicity, overall survival, local relapse- and progression-free survival. In the translational part of the study, we will evaluate the hypothesis that the baseline apparent diffusion coefficient (ADC) values of diffusion weighted MRI and its evolution 2 weeks after start of CRT, for the whole tumor as well as for intra-tumoral regions, is prognostic for residual tumor on the hysterectomy specimen. Discussion: Although MRI is already used to guide target delineation in brachytherapy, the EXIT-trial is the first to use this information to guide target delineation in external beam radiotherapy. Early therapy resistance prediction using DW-MRI opens a window for early treatment adaptation or further dose-escalation on tumors/intratumoral regions at risk for treatment failure

Prognostic significance of tumor-infiltrating lymphocytes in ductal carcinoma in situ of the breast

Tumor-infiltrating lymphocytes (TILs) provide prognostic value in invasive breast cancer and guidelines for their assessment have been published. This study aims to evaluate: (a) methods of TILs assessment, and (b) their prognostic significance in breast ductal carcinoma in situ (DCIS). Hematoxylin and eosin sections from two clinically annotated DCIS cohorts; a training set (n = 150 pure DCIS) and a validation set (n = 666 comprising 534 pure DCIS and 132 cases wherein DCIS and invasive breast carcinoma were co-existent) were assessed. Seven different scoring methods were applied to the training set to identify the most optimal reproducible method associated with strongest prognostic value. Among different methods, TILs touching ducts' basement membrane or away from it by one lymphocyte cell thickness provided the strongest significant association with outcome and highest concordance rate [inter-cluster correlation coefficient = 0.95]. Assessment of periductal TILs at increasing distances from DCIS (0.2 , 0.5 , and 1 mm) as well as percent of stromal TILs were practically challenging and showed lower concordance rates than touching TILs. TILs hotspots and lymphoid follicles did not show prognostic significance. Within the pure DCIS validation set, dense TILs were associated with younger age, symptomatic presentation, larger size, higher nuclear grade, comedo necrosis and estrogen receptor negativity as well as shorter recurrence-free interval (p = 0.002). In multivariate survival analysis, dense TILs were independent predictor of shorter recurrence-free interval (p = 0.002) in patients treated with breast conservation. DCIS associated with invasive carcinoma showed denser TILs than pure DCIS (p = 9.0 × 10-13). Dense TILs is an independent prognostic variable in DCIS. Touching TILs provides a reproducible method for their assessment that can potentially be used to guide management