Accuracy of [(18)Fluorine]-Fluoro-2-Deoxy-D-Glucose Positron Emission Tomography-Computed Tomography Response Assessment Following (Chemo) radiotherapy for Locally Advanced Laryngeal/Hypopharyngeal Carcinoma

Introduction: The accuracy of response assessment positron emission tomography (PET)-computed tomography (CT) following radiotherapy with or without chemotherapy for laryngeal/hypopharyngeal squamous cell carcinoma is uncertain. Methods: In all, 35 patients with laryngeal or hypopharyngeal squamous cell carcinoma who were treated between 2009 and 2014 with (chemo)radiotherapy were identified. The accuracy of response assessment PET-CT was made by correlation with clinical follow-up and pathological findings. Results: Of the 35 patients, 20 (57%) had an overall complete metabolic response. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for response assessment [18Fluorine]-fluoro-2-deoxy-d-glucose (FDG) PET-CT for primary and nodal sites, respectively, were 100%, 73%, 46%, and 100% and 83%, 95%, 83%, and 95%. Conclusions: Response assessment FDG PET-CT following (chemo)radiotherapy for laryngeal and hypopharyngeal carcinomas has a high NPV for both primary site and lymph nodes and can be used to guide treatment decisions. The PPV of residual FDG uptake at the primary tumour site is limited and requires examination and biopsy confirmation

Programmed Death-Ligand 1 Expression in Lung Cancer and Paired Brain Metastases-a Single-Center Study in 190 Patients.

Expression of programmed death-ligand 1 (PD-L1) is the only routinely used tissue biomarker for predicting response to programmed cell death protein 1/PD-L1 inhibitors. It is to date unclear whether PD-L1 expression is preserved in brain metastases (BMs). In this single-center, retrospective study, we evaluated PD-L1 expression using the SP263 assay in consecutively resected BMs of lung carcinomas and paired primary tumors, diagnosed from 2000 to 2015, with correlation to clinicopathological and molecular tumor and patient characteristics. PD-L1 tumor proportional score (TPS) could be evaluated on whole tissue slides in 191 BMs and 84 paired primary lung carcinomas. PD-L1 TPS was less than 1% in 113 of 191 (59.2%), 1% to 49% in 34 of 191 (17.8%), and greater than or equal to 50% in 44 of 191 (23.0%) BMs. TPS was concordant between BMs and paired primary lung carcinomas in most cases, with discordance regarding the clinically relevant cutoffs at 1% and 50% in 18 of 84 patients (21.4%). Four of 18 discordant cases had no shared mutations between the primary lung carcinoma and BM. Intratumoral heterogeneity, as assessed using tissue microarray cores, was only significant at the primary site (p <sub>Wilcoxon signed rank</sub> = 0.002) with higher PD-L1 TPS at the infiltration front (mean = 40.4%, interquartile range: 0%-90%). Neither TPS greater than or equal to 1% nor TPS greater than or equal to 50% nor discordance between the primary lung carcinoma and BMs had prognostic significance regarding overall survival or BM-specific overall survival. PD-L1 expression was mostly concordant between primary lung carcinoma and its BM and between resections of BM and stereotactic biopsies, mirrored by tissue microarray cores. Differences in PD-L1 TPS existed primarily in cases with TPS greater than 10%, for which also human assessment tends to be most error prone

Developing and Evaluating a Musical Attention Control Training Game Application

Musical attention control training (MACT) is a Neurologic Music Therapy (NMT) technique to strengthen attention skills for people who may have attention defi-cits, for instance related to ADHD or Parkinson Disease (PD), activating different parts of the brain and stimulating neural connectivity. While multiple interventions per week would enhance the effect of MACT, attending sev-eral sessions a week with a therapist can be challenging. Applied game interventions implementing MACT, which can be played at home, could offer complementary training to the limited number of therapy sessions. While applied games have been shown to facilitate successful interventions for cognitive impairments, to date no game exists based on MACT. We propose a novel approach to research the plausibility of applied games to support NMT, conclude game requirements for the specific needs of People with PD (PwPD), and introduce a game that emulates a MACT session. We carried out a pilot experiment to gauge how users interact with the game and its efficacy in attention control training with non-PD participants, letting them play 10 game intervention sessions within two weeks. Although no significant short-term attention effects were observed in this timeframe, user evaluations and metrics of game performance suggest that gamified MACT could be a promising supplement to conventional MACT for improving attention skills to optimize quality of life of PwPD

Internet gaming disorder and problematic internet use: the links between cyber-bullying, aggression, loneliness and psychiatric comorbidities

Aims: To compare adolescents clinically diagnosed with Internet Gaming Disorder (IGD) and problematic internet use (PIU) in terms of cyberbullying, aggression, and loneliness. Methods: Male adolescent patients (N=124, 14.3±1.7 years) with Internet Addiction Scale (IAS) scores ≥50 were clinically interviewed for IGD in utilizing DSM-5 criteria. Patients without full IGD criteria were included as PIU comparisons. Clinical variables were assessed using the second version of the Revised Cyber Bullying Inventory, short-form of the UCLA Loneliness Scale, Buss Perry Aggression Questionnaire, Child Depression Inventory, and Screen for Child Anxiety Related Emotional Disorders. Results: Compared to individuals with PIU, those with IGD were significantly more likely to have attention-deficit hyperactivity disorder, higher social phobia scores, higher cyberbullying scores, higher loneliness scores, been a cyberbully, and been a cyberbully victim. Conclusion: Male adolescents with IGD have higher rates of psychiatric comorbidity, perceived loneliness, cyberbullying, and being a victim of cyberbullying than those with PIU. Future studies could evaluate these predictors of transition from PIU to IGD in large cohort samples

Actinomycosis of the parotid masquerading as malignant neoplasm.

BACKGROUND: Primary actinomycosis of the parotid gland is of rare occurrence and can mimic a malignant neoplasm both clinically as well as radiologically. CASE PRESENTATION: We present here a case of primary actinomycosis of the parotid gland presenting with a parotid mass lesion with erosion of skull bones. CONCLUSIONS: Clinical presentation of cervico-facial actinomycosis is characterized by the presence of a suppurative or indurative mass with discharging sinuses. The lesion demonstrates characteristic features on fine needle aspiration cytology and histology, however at times the findings are equivocal

A Configurable CEGAR Framework with Interpolation-Based Refinements

International audienceCorrectness of software components in a distributed system is a key issue to ensure overall reliability. Formal verification techniques such as model checking can show design flaws at early stages of development. Abstraction is a key technique for reducing complexity by hiding information, which is not relevant for verification. Counterexample-Guided Abstraction Refinement (CEGAR) is a verification algorithm that starts from a coarse abstraction and refines it iteratively until the proper precision is obtained. Many abstraction types and refinement strategies exist for systems with different characteristics. In this paper we show how these algorithms can be combined into a configurable CEGAR framework. In our framework we also present a new CEGAR configuration based on a combination of abstractions, being able to perform better for certain models. We demonstrate the use of the framework by comparing several configurations of the algorithms on various problems, identifying their advantages and shortcomings

The M235T Polymorphism in the AGT Gene and CHD Risk: Evidence of a Hardy-Weinberg Equilibrium Violation and Publication Bias in a Meta-Analysis

BACKGROUND: The M235T polymorphism in the AGT gene has been related to an increased risk of hypertension. This finding may also suggest an increased risk of coronary heart disease (CHD). METHODOLOGY/PRINCIPAL FINDINGS: A case-cohort study was conducted in 1,732 unrelated middle-age women (210 CHD cases and 1,522 controls) from a prospective cohort of 15,236 initially healthy Dutch women. We applied a Cox proportional hazards model to study the association of the polymorphism with acute myocardial infarction (AMI) (n = 71) and CHD. In the case-cohort study, no increased risk for CHD was found under the additive genetic model (hazard ratio [HR] = 1.20; 95% confidence interval [CI], 0.86 to 1.68; P = 0.28). This result was not changed by adjustment (HR = 1.17; 95% CI, 0.83 to 1.64; P = 0.38) nor by using dominant, recessive and pairwise genetic models. Analyses for AMI risk under the additive genetic model also did not show any statistically significant association (crude HR = 1.14; 95% CI, 0.93 to 1.39; P = 0.20). To evaluate the association, a comprehensive systematic review and meta-analysis were undertaken of all studies published up to February 2007 (searched through PubMed/MEDLINE, Web of Science and EMBASE). The meta-analysis (38 studies with 13284 cases and 18722 controls) showed a per-allele odds ratio (OR) of 1.08 (95% CI, 1.01 to 1.15; P = 0.02). Moderate to large levels of heterogeneity were identified between studies. Hardy-Weinberg equilibrium (HWE) violation and the mean age of cases were statistically significant sources of the observed variation. In a stratum of non-HWE violation studies, there was no effect. An asymmetric funnel plot, the Egger's test (P = 0.066), and the Begg-Mazumdar test (P = 0.074) were all suggestive of the presence of publication bias. CONCLUSIONS/SIGNIFICANCE: The pooled OR of the present meta-analysis, including our own data, presented evidence that there is an increase in the risk of CHD conferred by the M235T variant of the AGT gene. However, the relevance of this weakly positive overall association remains uncertain because it may be due to various residual biases, including HWE-violation and publication biases