Coronary collateral circulation exerts protective effects on myocardial ischemia due to coronary artery disease (CAD) and can be promoted by exercise (E) with heparin (H) co-administration. Whether this arteriogenetic effects is accompanied by functional improvement of left ventricle (LV) during stress remains unknown. To establish the stress-induced functional effects on LV regional and global function of 2-week cycle of H+E in patients with “no-option” CAD. In a prospective, single-center, double-blind, randomized, parallel-group study we recruited 32 “no-option” patients (27 males; mean age of 61±8 years), with stable angina and CTO, refractory to OMT, not suitable for revascularization and with E-induced ischemia. All underwent 2-week cycle of E (2 E test per day, 5 days a week) and were pre-treated with i.v. 0.9% saline or unfractionated H (100 IU/kg up to maximum of 5.000IU, 10 min prior to E). Canadian Class Score (CCS) and 12-lead E-ECG for time-to-1 mm ST-segment depression were assessed at entry and after treatment. LV function was evaluated during treadmill exercise with conventional and advanced imaging indices: Wall Motion Score Index (WMSI); Ejection Fraction (EF); Force (systolic blood pressure/end-systolic volume); Global Longitudinal Strain (GLS). Post-treatment exercise-time and CCS improved in both groups. In H+E patients exercise-time improved from 369.8±107.8 sec to 475.3±114.6 sec (p=0.001) while in E patients improved from 384±152.7 sec to 464.8±134.1 sec (p=0.019). CCS score changed in H+E from 2.6±0.7 to 1.9±0.7 (p=0.000), and in E group from 2.4±0.7 to 2.1±0.9 (p=0.046). At peak exercise, H+E was different from E group for EF and GLS (see Table). Effects of H+E on SE parameters H+E p P+E p *H+E vs P+E STRESS Time 0 vs Time 1 Time 0 vs Time 1 Time 0 Time 1 WMSI 1.377 vs 1.279 0.005 1.404 vs 1.376 0.290 0.626 0.255 EF (%) 60.9 vs 64.8 0.016 61.2 vs 57.8 0.284 0.943 0.016 Force (mmHg/mL) 6.36 vs 6.5 0.158 5.82 vs 4.68 0.209 0.760 0.098 GLS (%) −16.96 vs −18.50 0.001 −15.79 vs −15.60 0.380 0.325 0.027 SE = stress echocardiography; H+E = heparin+exercise; P+E = placebo+exercise; Time 0 = before randomization; Time 1 = after 2-week therapy cycle. *p values. A 2-week, H+E cycle is associated with improvement in regional and global LV function during exercise, concordantly shown by conventional (WMSI, EF) and advanced (GLS) echocardiographic indices of LV function. This integrates and supplements the classical objective index based on ST-segment depression, unable to localize and quantify the functional consequences of therapy on myocardial ischemia.

Heart failure is a major cause of morbidity, mortality and re-hospitalizations and is highly prevalent in myocardial infarction survivors. Cardiac rehabilitation based on exercise training and heart failure self-care counseling have each been shown to improve clinical status and clinical outcomes. We designed our study with aim to evaluate the usefulness of exercise based in house cardiac rehabilitation/ secondary prevention program in patients with heart failure with mid-range ejection fraction (HFmrEF) after myocardial infarction. Out of 2753 patients who were admitted to our three weeks in- hospital secondary prevention program – exercised based cardiac rehabilitation, we analyze a total of 219 patients who were admitted early after coronary revascularization (percutaneus coronary interventions or coronary bypass surgery) with HFmrEF. The majority of patients were males (68%). Risk factors and co morbidities were noted. Patients were selected for exercise training after six minute walking test or exercise stress test (cardiopulmonary dominantly to evaluate unexpected exertional dyspnea). After 3 weeks in house cardiac rehabilitation the patients were re-tested. The major comorbidities in our patient population were as follows: hypertension, diabetes and dyslipidemia. Six minutes walking test was performed and the total distance walked ranged from 120 to 480 meters and the beginning of the program. Patient had 7 -days a week training program. After the 3 weeks in hospital exercise rehabilitation the improvement in the test was ∼32%. Cardiopulmonary test showed also improvement of functional capacity.We noted several rhythm disturbance complications by telemetry (VES, SVES). None had acutisation of heart failure (with peripheral edema and congestion). All patients fulfilled cardiac rehabilitation program. Supervised multidisciplinary cardiac rehabilitation program, including an individualized exercise component is effective and can improve functional status and exercise tolerance in patient with HFmrEF after myocardial infarction.

Current guidelines do not recommend thrombolytic therapy for the treatment of intermediate-risk pulmonary embolism (PE) because of the tight balance between the benefit and safety with classic protocols. The aim of this study was to compare the new thrombolytic protocol with lower-dose slow-infusion (LDSI) of tissue plasminogen activator (tPA) to classic 2-hours tPA infusion protocol or no-reperfusion in patients with intermediate-high risk PE with higher bleeding risk regarding 30-day efficacy and safety. Among 849 patients with PE from the Serbian multicenter registry, 469 patients who fulfilled criteria for intermediate-risk PE were involved in the study. After propensity score matching 425 patients [263 (61.9%), 99 (23.3%) and 63 (14.8%) were treated with no-reperfusion, classic tPA protocol (100 mg for 2 hours) and LDSI of tPA (2–5 mg/hour either vie local catheter or systemic venous infusion with dose range of 25–50 mg)]. The basic characteristics of patients were well balanced between groups except that patients treated with LDSI of tPA had significantly higher usage of drugs which can be associated to bleeding and more previous bleeding events. Thirty day all-cause and PE-caused mortality and 7-day major bleeding were the main efficacy and safety end-points, respectively. All-cause and PE-cause 30-day mortality were 8.7% vs 16.2% vs 1.6% (Log rank p=0.007) and 4.5% vs 11.0% vs 0.0% (Log rank p=0.008) in patients with no-reperfusion, classic tPA protocol and LDSI of tPA protocol, respectively. Major bleeding at 7 days were 2.7% vs 8.1% vs 14.3% (Log rank p=0.001) in patients with no-reperfusion, classic tPA protocol and LDSI of tPA protocol, respectively. There was one fatal intracranial bleeding during catheter infusion of tPA. Lower-dose slow-infusion of tPA protocol decreased significantly all-cause and PE-cause mortality at 30-day at the cost of excess of non-fatal major bleeding at 7-day in patients with intermediate-risk PE and higher risk for bleeding. None

Receiver functions are sensitive to sharp seismic velocity variations with depth and are commonly used to constrain crustal thickness. The H–κ stacking method of Zhu & Kanamori is often used to constrain both the crustal thickness (H) and ${V_P}$/${V_S}$ ratio ($\kappa $) beneath a seismic station using P-to-s converted waves (Ps). However, traditional H–κ stacks require an assumption of average crustal velocity (usually ${V_P}$). Additionally, large amplitude reverberations from low velocity shallow layers, such as sedimentary basins, can overprint sought-after crustal signals, rendering traditional H–$\ \kappa $ stacking uninterpretable. We overcome these difficulties in two ways. When S-wave reverberations from sediment are present, they are removed by applying a resonance removal filter allowing crustal signals to be clarified and interpreted. We also combine complementary Ps receiver functions, Sp receiver functions, and the post-critical P-wave reflection from the Moho (SPmp) to remove the dependence on an assumed average crustal ${V_P}$. By correcting for sediment and combining multiple data sets, the crustal thickness, average crustal P-wave velocity and crustal ${V_P}$/${V_S}$ ratio is constrained in geological regions where traditional H–$\ \kappa $ stacking fails, without making an initial P-wave velocity assumption or suffering from contamination by sedimentary reverberations.

The scope and scale of biological data are increasing at an exponential rate, as technologies like next-generation sequencing are becoming radically cheaper and more prevalent. Over the last two decades, the cost of sequencing a genome has dropped from $100 million to nearly $100—a factor of over 106—and the amount of data to be analyzed has increased proportionally. Yet, as Moore’s Law continues to slow, computational biologists can no longer rely on computing hardware to compensate for the ever-increasing size of biological datasets. In a field where many researchers are primarily focused on biological analysis over computational optimization, the unfortunate solution to this problem is often to simply buy larger and faster machines. Here, we introduce Seq, the first language tailored specifically to bioinformatics, which marries the ease and productivity of Python with C-like performance. Seq starts with a subset of Python—and is in many cases a drop-in replacement—yet also incorporates novel bioinformatics- and computational genomics-oriented data types, language constructs and optimizations. Seq enables users to write high-level, Pythonic code without having to worry about low-level or domain-specific optimizations, and allows for the seamless expression of the algorithms, idioms and patterns found in many genomics or bioinformatics applications. We evaluated Seq on several standard computational genomics tasks like reverse complementation, k-mer manipulation, sequence pattern matching and large genomic index queries. On equivalent CPython code, Seq attains a performance improvement of up to two orders of magnitude, and a 160× improvement once domain-specific language features and optimizations are used. With parallelism, we demonstrate up to a 650× improvement. Compared to optimized C++ code, which is already difficult for most biologists to produce, Seq frequently attains up to a 2× improvement, and with shorter, cleaner code. Thus, Seq opens the door to an age of democratization of highly-optimized bioinformatics software.

Many users need social media platforms to improve business. The usage of those platforms is usually focused on the marketing and customer targeting. Platforms like Facebook, Instagram or YouTube give their users a large number of reports and analytic tools. Public figures and organizations have a large number of followers who generate a significant number of activities. This paper focuses on the use of Facebook's geography analytic in the process of events planning. The problem is formulated as a combinatorial optimization problem. Data from social media platforms are used as an input to nature-inspired optimization algorithm. A public data set has been created with cities from 20 European countries. An adjusted genetic algorithm (AGA) is proposed. The greedy approach and AGA are compared on real data from several Facebook pages and on the created public dataset. The genetic algorithm shows better results and it gives the same solution as an exhaustive search for smaller instances.

The planning of concert tours can be a challenging process which requires a large amount of data to be analyzed. The greatest profit cannot be obtained only by maximizing the expected number of visitors. However, most of the organizers mainly focus on that part of planning. To achieve the maximum profit possible, organizers must include other data in their analysis. Social media play a powerful role in music industry. Most of the mentioned data can be found online on social media like Facebook, YouTube or Instagram. Such data can be found in analytic sections of fan or event pages. In this paper, algorithms for tour planning have been introduced by using above mentioned data. Proposed algorithms are based on heuristic methods such as simulated annealing and genetic algorithm. A clustering based method is also implemented. Aforementioned algorithms were tested on real-world instances from Facebook fan page analytics and use number of fans and distance between cities.

Distribution network power flow (DNPF) is a core application of distribution management system (DMS). Two methods to implement fast DNPF are using Newton-Raphson (NR) approach and current iteration (CI) approach. In distribution systems with high penetration of renewable energy sources both methods must be able to model PV nodes correctly and efficiently. This paper explores implementations of NR DNPF and CI DNPF, their execution time and performance in networks with numerous distributed generators.

For unstructured environments, multi-leg platforms such as hexapods, introduce better stability and adaptation during the moving in a more complex environment. The common hexapod robots, which are controlled by discrete conventional microcontrollers would require new chip replacement due to I/O constraint. With an FPGA, the user can scale design and include new functionality later in the design process without buying new additional hardware. In this paper, we introduce the hybrid architecture as a combination of FPGA and microcontroller design. The goal of this work is to extend context arbitration of a fuzzy behavior-based approach for hexapod robot navigation at the FPGA device. Verilog has been used to develop FLC on FPGA. The controller algorithm is developed and implemented on FPGA Altera Cyclone IV board. An experimental evaluation of hexapod autonomous navigation at a rough terrain presents advantages of this hierarchy approach for real-time robot embedded systems.

Abstract Background BRAF genomic alterations (GA) occur in multiple tumor types and BRAF/MEK targeted therapies are approved in melanoma and NSCLC. Diverse mechanisms of AR to these therapies have been proposed but have not been comprehensively assessed. Methods Hybrid-capture based comprehensive genomic profiling (CGP) was performed on FFPE (n = 228,629) or blood-based cell free DNA (cfDNA, n = 15,069) samples for 222,952 patients (pts). Tumor mutational burden (TMB) was determined on 0.8-1.1 Mbp of sequenced DNA. Samples without evidence of tumor DNA or known to have not received RAF/MEK inhibitors were excluded. Paired samples were collected >60 days apart (median 523, range 71-5571). Results Paired samples with BRAF V600E (64%) or other activating BRAF GA (36%) were available for 154 pts with NSCLC (20%), melanoma (19%), CRC (15%) myeloma (8.4%) glioma (7.1%) or other (30%) cancers. Acquired GA previously described preclinically or clinically including in BRAF, KRAS, NRAS, MEK1, PIK3CA, PTEN, MET, and CCND1 occurred in 34 cases (Table). 56 additional cases had reportable acquired GA in other genes (eg. STK11, NF1). Median TMB was 4.0 vs 5.2 mut/Mb in the first vs second sample (p = 0.23). In 12% of cases (9 tissue, 9 cfDNA) a BRAF GA was not detected in the second sample. Most AR mechanisms (MET amp, KRAS mut, secondary BRAF GA) were tumor agnostic, but PIK3CA and PTEN GA were enriched in brain samples and absent in CRC, and NRAS mut were exclusive to melanoma (Table). Treatment status was available for a subset of cases. Notably V600E CRC, NSCLC and melanoma each had acquired MET amp post-dabrafenib + trametinib, and a V600E myeloma had acquired MEK C121S post-trametinib + vemurafenib. Additional clinical data will be presented. Table: 1878PD . Potential AR mechanism No. cases# AR subtypes Disease Histologies Associated Primary BRAF GA Biopsy location * KRAS mut 7 G12D (2), G12R, G12V, G13D, Q61H, K117N CRC (2), NSCLC (2), cholangiocarcinoma, multiple myeloma, CLL V600E (6), G466A omentum (2), liver NRAS mut 4 G12C, G13R, G13R/Q61H, Q61H/K melanoma (4) V600E (2), V600R, G469A brain (1), lymph node (1), soft tissue (1) NRAS amp 1 amp estimated copies: 41 NSCLC V600E pericardial fluid Secondary BRAF GA 10 N-terminal deletion exons 2-8 (6), duplications exons 10-18, L505H, N581I/D594G, amp estimated copies: 6 NSCLC (4), CRC (2), melanoma (2), multiple myeloma, pancreatic V600E (9), G466A liver (3), lymph node (2), lung, abdominal wall, brain MEK1 mut 1 C121S multiple myeloma V600E NA PIK3CA mut 5 H1047R (2), G1049R, R88Q, S405F glioma (3), NSCLC, thyroid V600E (3), N486_T491>K, R506_K507insVLR brain (4), lung PTEN GA 5 E7fs * , R130 * , G129R, splice site 165-1G>A, loss melanoma (2), glioma, NSCLC, UP neuroendocrine V600E, V600K, R506_K507insVLR, KHDRBS2-BRAF fusion brain (2), abdomen, soft tissue CCND1 amp 2 amp estimated copies: 9, 10 NSCLC, thyroid V600E, G464V brain, pleural fluid MET amp 4 amp estimated copies: 12, 14, 15, 56 NSCLC, CRC, melanoma, UP adenocarcinoma V600E (4) lymph node, colon, brain, liver * Indicated for tissue samples only (NA= not applicable); #5 cases had AR alterations in multiple genes included here; NSCLC: non-small cell lung cancer, CRC: colorectal carcinoma; CLL: chronic lymphocytic leukemia; UP: unknown primary; AR: acquired resistance; mut: mutation; amp: amplification. Conclusions Novel and previously observed potential AR alterations in paired BRAF altered clinical samples were detected using CGP. Most AR mechanisms appeared independent of tumor type and biopsy site. Additional clinical studies to explore effective treatments for these AR subsets are needed. Legal entity responsible for the study The authors. Funding Foundation Medicine. Disclosure F. Pietrantonio: Advisory / Consultancy: Roche; Advisory / Consultancy: Amgen; Advisory / Consultancy: Eli-Lily; Advisory / Consultancy: Bayer; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Servier; Advisory / Consultancy: Merck Serono. J. Lee: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine; Shareholder / Stockholder / Stock options: Roche. L. Boussemart: Advisory / Consultancy: Novartis; Advisory / Consultancy: Pierre Fabre. G. Srkalovic: Speaker Bureau / Expert testimony: Foundation Medicine. R. Madison: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine; Shareholder / Stockholder / Stock options: Roche. J.S. Ross: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine; Shareholder / Stockholder / Stock options: Roche. V.A. Miller: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine; Shareholder / Stockholder / Stock options: Roche; Advisory / Consultancy: Revolution Medicines. B.M. Alexander: Leadership role, Full / Part-time employment: Foundation Medicine; Shareholder / Stockholder / Stock options: Roche. S.M. Ali: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine; Shareholder / Stockholder / Stock options: Roche. A.B. Schrock: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine; Shareholder / Stockholder / Stock options: Roche. All other authors have declared no conflicts of interest.