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.

Abstract Background An optimal adjuvant treatment of HER2 positive breast cancer includes the initiation of trastuzumab within 6 months after the surgery. However, due to limited resources and waiting lists, this timeframe is often exceeded in developing countries. We previously reported short-term outcomes of a time-optimal versus delayed postoperative initiation of trastuzumab in women with HER2 positive, non-metastatic, neoadjuvant naive breast cancer. Here, we report an extended follow-up, summarizing outcomes of our cohorts. Methods We included 223 consecutive women with surgically treated, non-metastatic, neoadjuvant naive, HER2 positive breast cancer from 2009 to 2011, from four institutions in Bosnia and Herzegovina. Patients were assigned to a time-optimal group (TOG), or a delayed group 1 (DG1), or a delayed group 2 (DG2), depending on whether their adjuvant trastuzumab was initiated 6 months, or 6-12 months, or more than 12 months after the surgery, respectively. A cut-off point for the follow-up was January 2019. We compared clinical outcomes between the groups, taking into account lymph node status. Results The patient’s median age was 55 (range 27-80) years. Mean follow-up period was 67 (range 4-109) months. Node-negative disease was found in 38.6% patients overall. 37% (TOG) patients received trastuzumab within 6 months, while 41% (DG1) received it within 6-12, and 22% (DG2) more than 12 months after their surgery. A higher number of node negative patients was found in the DG2 group compared to the TOG and DG1 groups (48%, 35%, and 36% respectively). 5-year DFS rate was 70.73% (TOG), 67.03% (DG1), and 62.00% (DG2). The OS rate was 78.05% (TOG), 75.82% (DG1), and 74.00% (DG2). Conclusions From the above, a conclusion can be made that patients with time-optimal initiation of adjuvant trastuzumab therapy had a higher 5-year DFS and OS rate compared to the delayed treatment initiation groups. Results of the DG1 and the DG2 group indicate that trastuzumab therapy shows a persistent benefit even if administered with a delay. Higher DFS and OS rates in the DG2 group could be explained by a higher number of node-negative low-risk, patients in this group. Legal entity responsible for the study The authors. Funding Roche. Disclosure S. Beslija: Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: Novartis; Advisory / Consultancy: MSD; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer. T. Ceric: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: MSD; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Novartis. B. Hasanbegovic: Advisory / Consultancy: Roche. A. Pasic: Advisory / Consultancy: Merck; Advisory / Consultancy: Sanofi. All other authors have declared no conflicts of interest.

Metastatic Leydig cell tumors (LCT) are rare, difficult to treat malignancies without known underlying molecular-genetic events. We profiled 27 LCT cases using NGS and immunohistochemistry. Our study identified TERT gene fusions as a main genetic alteration and a potential therapeutic target in LCT. TOP1 and AR expressions may guide decisions on chemo- and/or hormone therapy for selected individual patients. Objective: Metastatic Leydig cell tumors (LCT) are rare, difficult-to-treat malignancies without known underlying molecular–genetic events. An index case of metastatic LCT showed an LDLR–TERT gene fusion upon routine genetic profiling for detection of therapeutic targets, which was then followed by an investigation into a cohort of additional LCTs. Patients and Methods: Twenty-nine LCT (27 male and 2 female patients) were profiled using next-generation sequencing and immunohistochemistry. Results: TERT gene fusions were detected only in testicular metastatic LCTs, in 3 of 7 successfully analyzed cases (RMST:TERT,LDLR:TERT, and B4GALT5:TERT). TOP1 and CCND3 amplifications were identified in the case with a B4GALT5:TERT fusion. A TP53 mutation was detected in 1 metastatic tumor without a TERT fusion. Five primary (4 testicular and 1 ovarian) LCTs showed multiple gene amplifications, without a consistent pattern. A single metastatic ovarian LCT showed BAP1 mutation and copy number amplifications affecting the NPM1, PCM1, and SS18 genes. At the protein level, 4 of 7 metastatic and 6 of 10 primary testicular LCTs overexpressed Topo1. Androgen receptor was overexpressed in 10 of 13 primary testicular tumors and 2 of 5 metastatic testicular LCTs (without detectable ARv7 messenger RNA or ARv7 protein). Only 1 metastatic testicular LCT exhibited a high tumor mutational burden; all tested cases were microsatellite instability stable and did not express programmed cell death ligand 1. Conclusions: Our study for the first time identified TERT gene fusions as a main genetic alteration and a potential therapeutic target in metastatic LCTs. Topo1 and androgen receptor may guide decisions on chemotherapy and/or hormone therapy for selected individual patients.

The trajectory of a moving object may be extracted from video using image processing algorithms. However, the quality of the extracted information largely depends on the frame rate and exposure time of the camera, thus it is difficult to capture fast movement using slower and less expensive cameras. To this end, we propose to use an active modulated light source for object tracking, interacting with exposure times and subsampling existing frames. A prototype of a multi-functional active visual marker is presented in this paper. The system is based on the ESP-WROOM-32 microcontroller, which is configured to use various communication protocols, namely WiFi 802.11, RF 2.4 GHz GFSK and RS485. The microcontroller controls the RGB LED, which is used as light source. In addition, the system can be synchronized with the external real-time clock. The experimental results have illustrated the advantages and disadvantages of the designed active markers and pointed out the directions for future work and development.

Computer vision systems are frequently used for inspection and classification of products during manufacturing. Image processing and analysis allows non-invasive extraction of object features within an image and the classification of objects based on the extracted data. Shape, texture and color are typical features that can be extracted from an image and used for object recognition. In this paper, a method of detection, segmentation and classification of resistors captured in digital image, based on their nominal values, is presented. The process consists of the following steps: image segmentation, morphological image processing, representation and description of objects, object features extraction, classification of extracted data using support vector machines (SVM). Experimental results show that the proposed method exhibits solid performance and real-time operating capabilities.

Color vision deficiency is a surprisingly frequent vision impairment, but not considered to be a mayor eye disease due to being inherited condition and not progressive condition. However it poses serious restrictions on a visually impaired person because vision deficiency tests are commonly used to disqualify individuals affected by color vision deficiency from certain occupations. Color vision deficiency cannot be cured, thus it is important to develop suitable assistive technology to overcome the restrictions it poses. Virtual reality can project custom and separate images to both eyes in a real-time and thus enabling a new class of assistive technology that can deliver visual information in a highly customized manner. Virtual reality based assistive technology is promising for age-related macular degeneration, diabetic retinopathy and particularly for color vision deficiency. Virtual reality prototype is created based on a video see-through setup using commercial virtual reality headset and stereo camera. The prototype uses custom image processing to transform visual information from the camera to color vision deficiency friendly form. Time-domain color mapping real-time image processing is proposed to improve scores on standard color vision deficiency tests - Ishihara tests. Experiment is conducted to evaluate a protanope time-domain color mapping with sinusoidal envelope.

Introduction: Inappropriate design of experimental studies in medicine inevitably leads to inaccurate or false results, which serve as basis for erroneous and biased conclusions. Aim The aim of our study was to investigate prevalence of implementing basic principles of experimental design (local control, replication and randomization) in preclinical experimental studies, performed either on animals in vivo, or animal/human material in vitro. Material and Methods Preclinical experimental studies were retrieved from the PubMed database, and the sample for analysis was randomly chosen from the retrieved publications. Implementation rate of basic experimental research principles (local control, randomization and replication) was established by careful reading of the sampled publications and their checking against predefined criteria. Results Our study showed that only a minority of experimental preclinical studies had basic principles of design completely implemented (7%), while implementation rate of single aspects of appropriate experimental design varied from as low as 9% to maximum 86%. Average impact factor of the surveyed studies was high, and publication date relatively recent, suggesting generalizability of our results to highly ranked contemporary journals. Conclusion Prevalence of experimental preclinical studies that did not implement completely basic principles of research design is high, raising suspicion to validity of their results. If incorrect and biased, results of published studies may mislead authors of future studies and cause conduction of fruitless research that will waste precious resources.

Nakagami-m probability density function (pdf) is one of the frequently used distributions for describing fast received signal variations in radio channels, obtained as a result of multipath phenomenon. It is foremost derived by assuming the most general multipath channel model but applying mathematical approximations. Afterward, it is derived without approximations, but based on dedicated physical models with many constraints. Consequently, neither approach can be considered both, universally applicable and exact. Accordingly, in this paper, a novel approach in deriving Nakagami-m pdf is provided, being based on fewer constraints on propagation phenomena than others. Herein, it is shown that Nakagami-m pdf can be obtained as a distribution of a Euclidean distance of a point orthogonally projected from homogeneous distributed n-dimensional hypersphere on N-dimensional space, where received signal envelope is interpreted as mentioned Euclidean distance, with $n$ being a total number of orthogonal multipath components which can reach the receiver in idealized condition and $N$ being a number of these components which reach the receiver in reality (with N < n).

The self-blast type circuit breaker has been developed to reduce mechanical operation energy by building up the pressure of arc extinguishing gas flow from the heat of the arc itself. Unlike a puffer type, breaking performance for self-blast type are influenced and sensitive by various factors inside interrupter parts, such as the nozzle structure, chamber shape as well as amplitude of short circuit current. These days, particularly, it has been difficult to secure a low current breaking performance as the circuit breaker has been compacted. The currents for breaking test duties belong to from 10% to 30% of the rated breaking current in accordance with IEC standard. Although the arc energy for interruption is lower than the rated breaking current test duties, the breaking performance could be lower than the tests because the transient recovery voltage (TRV) after the current zero is relatively high. The capability of interruption is related to dielectric recovery after the arc quenching. Therefore, a complex analytical method is needed to secure the breaking performance for the current and to improve the performance by using the limited gas flow inside the interrupter parts. In this paper, it described the techniques to verify breaking performance such as hot gas flow analysis and dielectric analysis. And it has studied a method for improving the performance with various design parameters using computational fluid dynamics (CFD) programs and high power laboratory test. Finally, this paper shows us the improvement of dielectric recovery performance for the self-blast type circuit breaker.