Matrices associated to two conservative discretizations of Riesz fractional operators and related multigrid solvers

In this article, we focus on a two-dimensional conservative steady-state Riesz fractional diffusion problem. As is typical for problems in conservative form, we adopt a finite volume (FV)-based discretization approach. Precisely, we use both classical FVs and the so-called finite volume elements (FVEs). While FVEs have already been applied in the context of fractional diffusion equations, classical FVs have only been applied in first-order discretizations. By exploiting the Toeplitz-like structure of the resulting coefficient matrices, we perform a qualitative study of their spectrum and conditioning through their symbol, leading to the design of a second-order FV discretization. This same information is leveraged to discuss parameter-free symbol-based multigrid methods for both discretizations. Tests on the approximation error and the performances of the considered solvers are given as well

Breakdown of the Central Synapses in C9orf72-Linked ALS/FTD

Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disease that leads to the death of motor and cortical neurons. The clinical manifestations of ALS are heterogenous, and efficacious treatments to significantly slow the progression of the disease are lacking. Cortical hyper-excitability is observed pre-symptomatically across disease-causative genetic variants, as well as in the early stages of sporadic ALS, and typically precedes motor neuron involvement and overt neurodegeneration. The causes of cortical hyper-excitability are not yet fully understood but is mainly agreed to be an early event. The identification of the nucleotide repeat expansion (GGGGCC)n in the C9ORF72 gene has provided evidence that ALS and another neurodegenerative disease, frontotemporal dementia (FTD), are part of a disease spectrum with common genetic origins. ALS and FTD are diseases in which synaptic dysfunction is reported throughout disease onset and stages of progression. It has become apparent that ALS/FTD-causative genes, such as C9ORF72, may have roles in maintaining the normal physiology of the synapse, as mutations in these genes often manifest in synaptic dysfunction. Here we review the dysfunctions of the central nervous system synapses associated with the nucleotide repeat expansion in C9ORF72 observed in patients, organismal, and cellular models of ALS and FTD

Wake Up and Talk with Me! In-the-Field Study of an Autonomous Interactive Wake Up Robot

12th International Conference, ICSR 2020, Golden, CO, USA, November 14–18, 2020In this paper, we present a robot that is designed to smoothly wake up a user in the morning. We created an autonomous interactive wake up robot that implements a wake up behavior that was selected through preliminary experiments. We conducted a user study to test the interactive robot and compared it to a baseline robot that behaves like a conventional alarm clock. We recruited 22 participants that agreed to bring the robot to their home and test it for two consecutive nights. The participants felt significantly less sleepy after waking up with the interactive robot, and reported significantly more intention to use the interactive robot

Factors Associated with Severe Late Toxicity After Concurrent Chemoradiation for Locally Advanced Head and Neck Cancer: An RTOG Analysis

Purpose Concurrent chemoradiotherapy (CCRT) for squamous cell carcinoma of the head and neck (SCCHN) increases both local tumor control and toxicity. This study evaluates clinical factors that are associated with and might predict severe late toxicity after CCRT. Methods Patients were analyzed from a subset of three previously reported RTOG trials of concurrent chemoradiotherapy for locally advanced SCCHN (RTOG 91-11; 97-03; and 99-14). Severe late toxicity was defined in this secondary analysis as chronic Grade 3-4 pharyngeal/laryngeal toxicity (RTOG/EORTC late toxicity scoring system) and/or requirement for a feeding tube ≥2 years after registration and/or potential treatment-related death (e.g. pneumonia) within 3 years. Case-control analysis was performed, with a multivariable logistic regression model that included pre-treatment and treatment potential factors. Results A total of 230 patients were evaluable for this analysis, 99 cases (patients with severe late toxicities) and 131 controls; thus 43% of evaluable patients had a severe late toxicity. On multivariable analysis, significant variables correlated with the development of severe late toxicity were older age (odds ratio 1.05 per year; p = 0.001); advanced T-stage (odds ratio 3.07; p=0.0036); larynx/hypopharynx primary site (odds ratio 4.17; p=0.0041); and neck dissection after chemo-RT (odds ratio 2.39; p=0.018). Conclusions Severe late toxicity following CCRT is common. Older age, advanced T-stage, and larynx/ hypopharynx primary site were strong independent risk American Society of Clinical Oncology. Machtay, M. et al: J. Clin. Oncol. 26 (21), 2008:3582-3589

Health-related quality of life and late morbidity in concurrent chemoradiation and radiotherapy alone in patients with locally advanced cervical carcinoma

Objective: Concurrent chemoradiation has improved survival of patients with cervical carcinoma. However, follow-up of randomized studies is relatively short and data on long term toxicity are scarce, as is information on their health-related quality of life. This study assesses and compares incidences of late side-effects among patients treated with radiotherapy or chemoradiation using two toxicity scoring systems, and investigates impact on health-related quality of life. Methods: Between 1985 and 1993, 114 patients underwent radiotherapy (n=39) or chemoradiation (n=75) for stage IIA-IVB cervical carcinoma. Late side-effects were scored retrospectively by reviewing medical charts using standardised checklists, focusing on bladder- and intestinal side effects. Health-related quality of life was assessed once using the EORTC QLQ-C30. Results: No significant differences in late treatment-related side-effects between radiotherapy and chemoradiation groups were found. Grade >= 2 toxicity was found in 33% (bladder), and in 6% (bowel). Only 1.8% had both grade 3-4 toxicity. Bladder syndrome with high urinary frequency, urine incontinence and small bowel toxicity had a significant impact on health-related quality of life. Conclusion: Grade 2 are relatively frequent late side effects in curatively treated patients, but are not enhanced by the addition of chemotherapy. Their negative impact on health-related quality of life stresses the importance of new radiation techniques, aiming at reduction of these side effects

Ipsilateral irradiation for well lateralized carcinomas of the oral cavity and oropharynx: results on tumor control and xerostomia

<p>Abstract</p> <p>Background</p> <p>In head and neck cancer, bilateral neck irradiation is the standard approach for many tumor locations and stages. Increasing knowledge on the pattern of nodal invasion leads to more precise targeting and normal tissue sparing. The aim of the present study was to evaluate the morbidity and tumor control for patients with well lateralized squamous cell carcinomas of the oral cavity and oropharynx treated with ipsilateral radiotherapy.</p> <p>Methods</p> <p>Twenty consecutive patients with lateralized carcinomas of the oral cavity and oropharynx were treated with a prospective management approach using ipsilateral irradiation between 2000 and 2007. This included 8 radical oropharyngeal and 12 postoperative oral cavity carcinomas, with Stage T1-T2, N0-N2b disease. The actuarial freedom from contralateral nodal recurrence was determined. Late xerostomia was evaluated using the European Organization for Research and Treatment of Cancer QLQ-H&N35 questionnaire and the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 3.</p> <p>Results</p> <p>At a median follow-up of 58 months, five-year overall survival and loco-regional control rates were 82.5% and 100%, respectively. No local or contralateral nodal recurrences were observed. Mean dose to the contralateral parotid gland was 4.72 Gy and to the contralateral submandibular gland was 15.30 Gy. Mean score for dry mouth was 28.1 on the 0-100 QLQ-H&N35 scale. According to CTCAE v3 scale, 87.5% of patients had grade 0-1 and 12.5% grade 2 subjective xerostomia. The unstimulated salivary flow was > 0.2 ml/min in 81.2% of patients and 0.1-0.2 ml/min in 19%. None of the patients showed grade 3 xerostomia.</p> <p>Conclusion</p> <p>In selected patients with early and moderate stages, well lateralized oral and oropharyngeal carcinomas, ipsilateral irradiation treatment of the primary site and ipsilateral neck spares salivary gland function without compromising loco-regional control.</p

Programmed Chemotherapy for Patients with Metastatic Unresectable Gastric Cancer

BACKGROUND: Recent advances in the treatment of metastatic unresectable gastric cancers (MGC) include the development of new antitumor drugs and new regimens for their use. However, the selection of individually designed regimens by gastric cancer (GC) subtype remains problematic. Here, we investigated the clinical usefulness of programmed chemotherapy. METHODOLOGY/PRINCIPAL FINDINGS: MGC patients were classified into three groups by clinical condition. We implemented a chemotherapy program consisting of S-1 combination regimens. Median survival time (MST) of level 1 patients was 416 days (95% CI: 313-506 days), with an overall response rate of 47%. MSTs of level 2 and 3 patients were 208 (95% CI: 153-287 days) and 95 days (95% CI: 28-136 days), respectively. Grade 3-4 toxicities were neutropenia in 12% and anorexia in 6%. All treatment- related toxicities were resolved, and no treatment-related deaths occurred. CONCLUSIONS/SIGNIFICANCE: This program provided reasonable selection of case-matching regimens and may improve the survival of patients with MGC. Further, it may represent the first clinical tool to provide efficient chemotherapy course selection for MGC. Ongoing analysis of newly developed drugs and regimens will allow the efficacy of this chemotherapy program to be improved

Phase 1/2 Dose Escalating Study of Twice-Monthly Pemetrexed and Gemcitabine in Patients with Advanced Cancer and Non-small Cell Lung Cancer

IntroductionPemetrexed is synergistic with gemcitabine in preclinical models of non-small cell lung cancer (NSCLC). The optimal dose and utility of gemcitabine and pemetrexed was evaluated in a dose-escalating study.MethodsThe phase 1 study included patients with advanced tumors, whereas the phase 2 study included patients with locally advanced or metastatic NSCLC. Gemcitabine was infused over 30 minutes, followed by pemetrexed administered over 10 minutes on day 1 of a 14-day cycle. Treatment continued for 12 cycles or until disease progression. All patients received folic acid, Vitamin B12, and steroid prophylaxis.ResultsMaximum tolerated dose was gemcitabine 1500 mg/m2, followed by pemetrexed 500 mg/m2. Fifty-three patients (29 male, 24 female) were enrolled in the phase 2 study. Response rate was 20.8% (95% CI: 0.108–0.341), and the clinical benefit rate (CR + PR + SD) was 64.2%. Median time to disease progression was 4.6 months (95% CI: 2.79–6.18), median survival was 10.1 month (95% CI: 5.95–14.09, censorship = 20.75%), and 1-year survival was 41.0%. Common grade 3 or 4 adverse events (% of patients) were neutropenia (28.3%), fatigue (22.6%), and febrile neutropenia (9.4%).ConclusionsTwice-monthly gemcitabine and pemetrexed was well tolerated, with overall survival and clinical benefit indicating disease activity in NSCLC patients

Combination therapy with docetaxel and S-1 as a first-line treatment in patients with advanced or recurrent gastric cancer: a retrospective analysis

<p>Abstract</p> <p>Background</p> <p>We performed a single-institution retrospective study to evaluate the efficacy and toxicities of combination therapy with docetaxel and S-1 in patients with advanced or recurrent gastric cancer.</p> <p>Methods</p> <p>Eighty-six patients with advanced or recurrent gastric cancer were enrolled. Patients received docetaxel, 40 mg/m², on day 1 and oral S-1, 80 mg/m²/day, on days 1 to 14 every 3 weeks.</p> <p>Results</p> <p>All 84 patients were assessable for response. The overall response rate was 52.4% (44/84) and the disease control rate was 96.4% (81/84). Median time to progression (TTP) and overall survival (OS) were 6.5 (95% CI, 4.8-8.1 months) and 15.1 months (95% CI, 11.7-18.5 months), respectively. The major toxicities were neutropenia, leukopenia, alopecia and anorexia. Grade 3 or 4 hematologic toxicities included neutropenia in 31 patients (36.0%), leukopenia in 27 (31.7%), febrile neutropenia in four (4.7%), and anemia in one (1.2%). Other grade 3 toxicities included anorexia in five patients (5.8%), and stomatitis, diarrhea and nausea in one each (1.2%). There was one treatment-related death (1.2%).</p> <p>Conclusion</p> <p>The combination of docetaxel and S-1 had good clinical activity with acceptable toxicity in patients with advanced or recurrent gastric cancer.</p