ParaPlan: A Tool for Parallel Reachability Analysis of Planar Polygonal Differential Inclusion Systems

Andrei Sandler, and Olga Tveretina, ‘ParaPlan: A Tool for Parallel Reachability Analysis of Planar Polygonal Differential Inclusion Systems’, in Patricia Bouyer, Andrea Orlandini and Pierluigi San Pietro, eds. Proceedings Eight International Symposium on Games, Automata, Logics and Formal Verification (GandALF 2017), Rome, Italy, 20-22 September 2017, Electronic Proceedings in Theoretical Computer Science, Vol. 256: 283-296, September 2017. © 2017 The Author(s). This work is licensed under the Creative Commons Attribution License CC BY 4.0 https://creativecommons.org/licenses/by/4.0/We present the ParaPlan tool which provides the reachability analysis of planar hybrid systems defined by differential inclusions (SPDI). It uses the parallelized and optimized version of the algorithm underlying the SPeeDI tool. The performance comparison demonstrates the speed-up of up to 83 times with respect to the sequential implementation on various benchmarks. Some of the benchmarks we used are randomly generated with the novel approach based on the partitioning of the plane with Voronoi diagrams

Ophthalmologic adverse events in childhood head and neck rhabdomyosarcoma survivors treated according to four different local treatment strategies

Introduction: Ophthalmological adverse events (OAEs) are known to frequently occur following local treatment for pediatric head and neck rhabdomyosarcoma (HNRMS). The exact nature of these OAEs and the burden they put on survivors is less well described. Moreover, it is suspected there might be differences in the prevalence and nature of OAEs depending on local treatment strategy applied: external beam radiation therapy with photons, external beam radiation therapy with protons, macroscopically radical surgery combined with brachytherapy, or microscopically radical surgery combined with external beam radiation therapy. Methods: We cross-sectionally assessed 98 HNRMS survivors with long (median 9 years) follow-up time, according to a predefined list of OAEs based on the Common Terminology Criteria for Adverse Events system. We added information from chart reviews on the nature and management of all OAEs scored grade ≥1. We describe the prevalence of OAEs for the different tumor sites and treatment strategies separately. Results: OAEs occurred following treatment of all HNRMS sites. The most frequently observed OAEs are eyelid abnormalities, dry eyes, and cataracts. Sixty-two percent of survivors had several different OAEs simultaneously. In 27 % of survivors additional (surgical) treatment of OAEs was required during follow-up. The patterns observed suggest a possible relationship between OAE type and treatment strategy. Conclusion: OAEs in HNRMS survivors confer a high burden of chronic toxicity. The simultaneous occurrence of multiple OAEs in individual survivors present a particularly challenging clinical scenario and demand specific expertise. We propose a standardized screening scheme to detect possible OAEs in asymptomatic survivors based on primary tumor localization

Maintenance therapy in NSCLC: why? To whom? Which agent?

Maintenance therapy is emerging as a treatment strategy in the management of advanced non small cell lung cancer (NSCLC). Initial trials addressing the question of duration of combination chemotherapy failed to show any overall survival benefit for the prolonged administration over a fixed number of cycles with an increased risk for cumulative toxicity. Nowadays several agents with different ways of administration and a different pattern of toxicity have been formally investigated in the maintenance setting. Maintenance strategies include continuing with an agent already present in the induction regimen or switching to a different one. Taking into consideration that no comparative trials of maintenance with different chemotherapy drugs or targeted agents have been conducted, the choice and the duration of maintenance agents is largely empirical. Furthermore, it is still unknown and it remains an open question if this approach needs to be proposed to every patient in the case of partial/complete response or stable disease after the induction therapy. Here, we critically review available data on maintenance treatment, discussing the possibility to tailor the right treatment to the right patient, in an attempt to optimize costs and benefits of an ever-growing panel of different treatment options

Facial deformation following treatment for pediatric head and neck rhabdomyosarcoma; the difference between treatment modalities. Results of a trans-Atlantic, multicenter cross-sectional cohort study

Background: The four different local therapy strategies used for head and neck rhabdomyosarcoma (HNRMS) include proton therapy (PT), photon therapy (RT), surgery with radiotherapy (Paris-method), and surgery with brachytherapy (AMORE). Local control and survival is comparable; however, the impact of these different treatments on facial deformation is still poorly understood. This study aims to quantify facial deformation and investigates the differences in facial deformation between treatment modalities. Methods: Across four European and North American institutions, HNRMS survivors treated between 1990 and 2017, more than 2 years post treatment, had a 3D photograph taken. Using dense surface modeling, we computed facial signatures for each survivor to show facial deformation relative to 35 age–sex–ethnicity-matched controls. Additionally, we computed individual facial asymmetry. Findings: A total of 173 HNRMS survivors were included, survivors showed significantly reduced facial growth (p <.001) compared to healthy controls. Partitioned by tumor site, there was reduced facial growth in survivors with nonparameningeal primaries (p =.002), and parameningeal primaries (p ≤.001), but not for orbital primaries (p =.080) All patients were significantly more asymmetric than healthy controls, independent of treatment modality (p ≤.001). There was significantly more facial deformation in orbital patients when comparing RT to AMORE (p =.046). In survivors with a parameningeal tumor, there was significantly less facial deformation in PT when compared to RT (p =.009) and Paris-method (p =.007). Interpretation: When selecting optimal treatment, musculoskeletal facial outcomes are an expected difference between treatment options. These anticipated differences are currently based on clinicians’ bias, expertise, and experience. These data supplement clinician judgment with an objective analysis highlighting the impact of patient age and tumor site between existing treatment options

A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Abstract: Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers

A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers

The Role of the Anesthesiologist during Magnetic Resonance-Guided Focused Ultrasound Thalamotomy for Tremor: A Single-Center Experience

Ablative incisionless neurosurgery has become possible through advances in focused ultrasound and magnetic resonance imaging (MRI). The great advantage of MRI-guided focused ultrasound (MRgFUS) is that the ablation is performed through an intact skull without surgery. Here, we review the new modality of MRgFUS for treating tremor and enlighten the role of the anesthesiologist in the unique procedural setting of the MRI suite. During the MRgFUS process, the patients should be awake and are required to cooperate with the medical staff to allow assessment of tremor reduction and potential occurrence of adverse effects. In addition, the patient’s head is immobilized inside the MRI tunnel for hours. This combination presents major challenges for the attending anesthesiologist, who is required to try to prevent pain and nausea and when present, to treat these symptoms. Anxiety, vertigo, and vomiting may occur during treatment and require urgent treatment. Here, we review the literature available on anesthetic management during the procedure and our own experience and provide recommendations based on our collected knowledge

Comparison of Rhabdomyolysis Markers in Patients Undergoing Bariatric Surgery with Propofol and Inhalation-based Anesthesia

Background: Rhabdomyolysis is a relatively uncommon, severe complication of anesthesia and surgery in the morbidly obese. As the use of propofol-based anesthesia has been associated with an increased risk of rhabdomyolysis and metabolic acidosis, this pilot study was designed to assess the effect of propofol anesthesia on the incidence of rhabdomyolysis in morbidly obese patients undergoing bariatric surgery. Methods: Thirty, morbidly obese patients (body mass index 43 ± 3\ua0kg/m) scheduled for bariatric laparoscopic sleeve gastrectomy were randomized to receive either propofol (P) or inhalational anesthetic (I)-based balanced general anesthesia. A sample of venous blood gas analysis including pH, bicarbonate concentrations, and calculated base excess was taken at the end of the operation. Creatine phosphokinase (CPK), troponin I, blood urea nitrogen, and creatinine plasma concentrations were measured at the end of the surgery and again 24\ua0h later. Results: All patients enrolled to the study completed it without significant complications. CPK, troponin I, blood urea nitrogen, and creatinine plasma concentrations at the end of the operation and at 24\ua0h, as well as the bicarbonate concentration and the base excess at the end of the operation were not significantly different between the two study groups. A statistically significant mild respiratory acidosis was noted in the inhalational anesthetic group (pH\ua07.30 ± 0.04 vs. 7.36 ± 0.02 in the propofol group) Conclusions: This small-size pilot study may suggest that propofol-based anesthesia is not related to increased incidence of rhabdomyolysis in morbidly obese patients undergoing short, uncomplicated bariatric surgery