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Purpose To report 3 cases of reversible epitheliopathy induced by A166—a human epidermal growth factor receptor (HER2)-targeted antibody-drug conjugate (ADC) therapy for resistant HER2 tumours. Methods Advanced HER2 tumour patients were enrolled in A166 phase I/II clinical trial using Bayesian logistic regression model dose escalation. Key exclusion criteria were ≥grade 2 (G2) corneal pathology, severe organ disease, and other cancer therapy within 4 weeks. Eye exams were performed at baseline, regularly scheduled intervals, and additionally upon A166-induced ocular symptoms. Topical therapy with autologous serum tears (ASTs) was implemented based on visual acuity, symptoms, and slit lamp exam. A166 was withheld if ≥G2 ocular toxicity developed; if status improved to ≤G1, A166 therapy was resumed. Visual acuity, corneal exam, and subjective comfort were recorded. Results After ≥2 cycles of A166, 6 eyes of 3/23 enrolled patients developed whorl pattern epitheliopathy suggestive of limbal stem cell (LSC) dysfunction requiring cessation of A166 despite positive tumour response. Patients 1 and 3 received 3.6 mg/kg A166 dose, and patient 2 received 3.0 mg/kg. Topical steroids (2/4 eyes) failed to improve epitheliopathy. Adding ASTs improved vision, ocular comfort, and whorl pattern epitheliopathy in 6/6 eyes within 3 weeks. Patient 1 continues to improve on ASTs; patient 2 withdrew from the study; and patient 3 resumed A166 therapy. Conclusion A166 precipitates LSC dysfunction-like epitheliopathy. Combination therapy including aggressive lubrication, withholding drug, and ASTs help reverse toxicity. Recognizing that ADC-induced epitheliopathy can respond to ocular management may enable cancer patients to continue lifesaving therapy.

With no expected vaccine for HIV in the near future, we aimed to define the current situation and challenges for pre- and post-exposure prophylaxis (PrEP and PEP) in Central and Eastern Europe (CEE). The Euroguidelines CEE Network Group members were invited to respond to a 27-item survey including questions on PrEP (response rate 91.6%). PrEP was licensed in 68.2%; 95 centers offered PrEP and the estimated number on PrEP was around 9000. It was available in daily (40.1%), on-demand (13.3%), or both forms (33.3%). The access rate was

Introduction:We evaluated the necessity of obtaining routine postoperative laboratory studies, such as complete blood count and basic metabolic panel, after robotic assisted radical prostat...

Introduction. Pleural synovial sarcoma (SS) is a rare type of mesenchymal tumor, that can easily be misdiagnosed. Case report. We presented a case of primary monophasic SS of the pleura in a middle-aged woman who initially presented with dyspnoea and a large pleural effusion. Computed tomography (CT) scans showed a large, well-demarcated right lung tumor mass. After a blind closed biopsy of the pleura, the tumor was misdiagnosed as adenocarcinoma and treated with chemotherapy but without response. The correct diagnosis was established after surgery and histological and immunohistochemical analyses. The diagnosis was fulfilled with cytogenetic analysis showing the typical translocation t (X,18). The tumor was completely extirpated during surgery. CT of the chest done four, and positron emission tomography done six months after surgery showed encapsulated re-active pleural effusion without tumor rest or relapse. In contrast, a CT scan done nine months after surgery showed an extrapulmonary soft-tissue mass in contact with the lower right lobe highly suspicious of tumor relapse. Surgery was performed, and the described mass was extirpated, but histological analysis showed no presence of malignant tissue. CT scan performed three months later showed no signs of the disease relapse. Conclusion. Considering that pleural SS can easily be misdiagnosed, immunohistochemical as well as cytogenetic analysis should always be performed in order to reach the proper diagnosis.

Purpose: The anti-CD33 antibody lintuzumab has modest activity against acute myeloid leukemia (AML). To increase its potency, lintuzumab was conjugated to actinium-225 (225Ac), a radionuclide yielding 4 α-particles. This first-in-human, phase I trial was conducted to determine the safety, pharmacology, and biological activity of 225Ac-lintuzumab. Patients and Methods: Eighteen patients (median age, 64 years; range, 45–80) with relapsed or refractory AML received a single infusion of 225Ac-lintuzumab at activities of 18.5 to 148 kBq/kg. Results: The maximum tolerated dose was 111 kBq/kg. Dose-limiting toxicities included myelosuppression lasting > 35 days in one patient receiving 148 kBq/kg and death from sepsis in two patients treated with 111 and 148 kBq/kg. Myelosuppression was the most common toxicity. Significant extramedullary toxicities were limited to transient grade 3 liver function abnormalities. Pharmacokinetics were determined by gamma counting serial whole blood, plasma, and urine samples at energy windows for the 225Ac daughters, francium-221 and bismuth-213. Two-phase elimination kinetics were seen with mean plasma t1/2 − α and t1/2 − β of 1.9 and 38 hours, respectively. Peripheral blood blasts were eliminated in 10 of 16 evaluable patients (63%) but only at doses of ≥ 37 kBq/kg. Bone marrow blasts were reduced in 10 of 15 evaluable patients (67%), including 3 patients with marrow blasts ≤ 5% and one patient with a morphologic leukemia-free state. Conclusions: Therapy for AML with the targeted α-particle generator 225Ac-lintuzumab was feasible with an acceptable safety profile. Elimination of circulating blasts or reductions in marrow blasts were observed across all dose levels.

Friction liner (FL) is a component of the brake carriage equipment for passenger railcars, included in risk class 1A, according to OMT 290/2000, with a normal service life of minimum 10 years (this does not take into account possible accidents or damage caused by the failure of other elements). According to the documentation, the friction linings (FL)s are checked every six months, and if any malfunctions that may endanger the proper functioning are found, the friction linings (FL)s are subjected to repair by replacing with new spare parts from the manufacturer, from import, which entails significant costs, either by technological operations of repair / reconditioning for reuse under maximum safety conditions. This paper presents a series of qualitative and quantitative results, by means of tables / graphs, obtained as a result of applying the technology of recovering the geometric shape (after wear in operation) using the Shielded Metal Arc Welding process (SMAW) [1], as a way of avoiding imports.

Cell-based approximations of PDE traffic models are widely used for traffic prediction and control. However, in order to represent the traffic state with good resolution, cell-based models often require a short cell length, which results in a very large number of states. We propose a new transition system traffic model, based on the front tracking method for solving the LWR PDE model. Assuming piecewise-linear flux function and piecewise-constant initial conditions, this model gives an exact solution. Furthermore, it is easier to extend, has fewer states and, although its dynamics are intrinsically hybrid, is faster to simulate than an equivalent cell-based approximation. The model is extended to enable handling moving bottlenecks as well as probabilistic traffic breakdowns and capacity drops at static bottlenecks. A control strategy that utilizes controlled moving bottlenecks for bottleneck decongestion is described and tested in simulation. It is shown that we are able to keep the static bottleneck in free flow by creating controlled moving bottlenecks at specific instances along on the road, and using them to regulate the incoming traffic flow.

Introduction: People living with HIV (PLWH) are at higher risk of poorer COVID-19 outcomes. Vaccination is a safe and effective method of prevention against many infectious diseases, including COVID-19. Here we investigate the strategies for national COVID-19 vaccination programmes across central and eastern Europe and the inclusion of PLWH in vaccination programmes. ----- Methods: The Euroguidelines in Central and Eastern Europe Network Group consists of experts in the field of infectious diseases from 24 countries in the region. Between 1 November 2020 and 19 March 2021 the group proceeded an on-line survey consisting of 20 questions. ----- Results: Twenty-two countries (out of 24 invited) participated in the survey and 20/22 countries in the period between December 2020 and March 2021 had already started their COVID-19 vaccination programme. In total, seven different vaccines were used by participating countries. In 17/21 countries (81%), vaccinated persons were centralized within the national registry. In 8/21 countries (38%) PLWH were prioritized for vaccination (the Czech Republic, Greece, Hungary, Lithuania, Montenegro, Romania, Slovakia, Slovenia) and the Czech Republic, Greece and Serbia had put in place national guidelines for vaccination of PLWH. In 14/20 countries (70%) vaccination was only provided by designated centres. Eighteen respondents (18/21; 85.7%) reported that they planned to follow up HIV patients vaccinated against COVID-19, mainly by measuring antibody levels and checking COVID-19 incidence (11/21; 52.3%). ----- Conclusions: This survey-based study suggests that there are significant differences in terms of prioritizing PLWH, the types of vaccines used, vaccination coverage, and the development and implementation of a vaccination programmes within the region. Regardless of heterogenicity and existing barriers within the region, systematic vaccination in PLWH should have the highest priority, especially in those with severe immunodeficiency, risk factors, and in the elderly, aiming for prompt and high vaccination coverage.

SNTFC CFR SA owns a fleet of 841 passenger coaches, which it maintains through usual overhauls and repairs at high safety levels provided by the national railway regulations and instructions. One of the most important systems of a wagon is the braking system. One part of this system is also the friction liner, its role being to support the friction gasket that applies the braking force on the brake disc. This friction liner is made of cast iron and is a component included in risk class 1A, according to OMT 290/2000, with a service life of 10 years. Depending on the degree of wear and safety in operation, one may decide to replace it with a new part or intervention to return to the initial dimensional shape. Considering the importance of this friction liner, a very precise analysis must be performed, and this should show the steps necessary to reintroduce the part into operation. The performed analysis is a welding reconditioning procedure, which must be applied with precision. The paper indicates all the stages and results we looked for by applying a reconditioning procedure for the particular situation of using the welding process by means of tables / graphs and of results obtained as of detailed works.

The paper presents and compares a series of standardized and non-standardized methods for determining the pre-heating temperature (Tpr) applied to reduce or eliminate negative effects resulting from the use of the welding process, such as cold cracking. The results of quantitative and qualitative comparisons of the various Tpr calculating/setting methodologies are presented, but the preheat temperature values obtained for a case study referring to 13CrMo4-5 steel welding, a heat-resistant steel used in the case of the pressure-generating products in the energy industry.

It is well known that in all industrial fields, various computer solutions are used to reduce the time required for the elaboration of documentation/design drawings/costs etc. In the field of welding there is a large number of such solutions, which makes that the choice of a certain IT solution becomes more difficult and must be based on the accuracy of the results obtained by application. In the study, there are several addresses of webpages containing such information solutions, their destination, and the results obtained by applying two online and one offline solutions that have the utility of predetermining the structure of the base material, the material addition and stitching material.

Robotic-assisted radical prostatectomy (RARP) is the most commonly performed surgery for prostate cancer. This is a study comparing differences in postoperative outcomes between pneumoperitoneum pressures of 15 mmHg and 12 mmHg. Retrospective chart review was performed on 400 patients undergoing RARP over a 5 year period. A combination of Fisher’s exact test and ANOVA were utilized for statistical analysis. Age, BMI, Gleason score, positive margin rate, complication rates, blood loss, and operative times were similar in both groups. Length of stay and postoperative ileus rates were significantly less in the 12 mmHg group (p

Biocompatible titanium alloys are increasingly being used to make custom medical implants using additive manufacturing processes. This paper considered the welding reconditioning of a titanium-alloy customized additive manufactured hip implant with several manufacturing defects. The personalized implants are made starting from a Computer-Aided Design (CAD) model as a direct result from the medical imaging investigations of the areas of interest. Then the customized implant is fabricated using an additive manufacturing process (in this case Powder Bed Fusion—Direct Metal Laser Sintering—DMLS). The analysis of the chemical composition values as well as the values of the mechanical properties of the samples obtained via DMLS additive manufacturing process, revealed that such a manufacturing process can be successfully used to make customized surgical implants. The mechanical properties values of the DMLS samples are approximately equal to those specified by the manufacturer of the titanium powder used for sintering. On average, the tensile strength was found to be 24.75% higher, while yield strength 22.7% higher than the values provided in the standard for surgical implants applications. In case the additive manufacturing process produces products with defects one might want to try and recover the implant due to costs and time constraints. The Tungsten Inert Gas (TIG) welding reconditioning process with ERTi-5 Ti64 rod for welding titanium alloys with a content of 6% aluminum and 4% vanadium filler material was used to restore the geometric characteristics as well as the functional properties of a custom hip medical prosthesis. After welding depositing successive layers of materials, the surfaces of the prosthesis were machined to restore the functional properties according to the characteristics of the original 3D model. A 3D scan was used to compare the geometrical characteristics between the original part and reconditioned one. Deviations were less than 1 mm and were acceptable from the medical point of view.

The paper aims to identify the effects on the geometrical configuration of the welding deposit caused by changes in the classical gas nozzle shape. The results obtained in the case of two geometrical shapes of the nozzles are presented after using continuous and pulsed current with short arc and spray arc transfer. The effects on the geometrical elements: deposition width (B) and reinforcement (h), are indicated in tabular and graphical shape.

This article investigates the use of a model-based neural-network for the traffic reconstruction problem using noisy measurements coming from probe vehicles. The traffic state is assumed to be the density only, modeled by a partial differential equation. There exist various methods for reconstructing the density in that case. However, none of them perform well with noise and very few deal with lagrangian measurements. This paper introduces a method that can reduce the processes of identification, reconstruction, prediction, and noise rejection into a single optimization problem. Numerical simulations, based either on a macroscopic or a microscopic model, show good performance for a moderate computational burden., 7 pages, 8 figures

In this paper we present a numerical study on control and observation of traffic flow using Lagrangian measurements and actuators. We investigate the effect of some basic control and observation schemes using probe and actuated vehicles within the flow. The aim is to show the effect of the state reconstruction on the efficiency of the control, compared to the case using full information about the traffic. The effectiveness of the proposed state reconstruction and control algorithms is demonstrated in simulations. They show that control using the reconstructed state approaches the full-information control when the gap between the connected vehicles is not too large, reducing the delay by more than $60\%$ when the gap between the sensor vehicles is $1.25$~km on average, compared to a delay reduction of almost $80\%$ in the full-information control case. %It shows that the reconstruction is well achieved if the distance between two connected and autonomous vehicles is not too large (more than 1 vehicle per kilometer). %We also show that it is possible to further improve the control performance by employing a simple adaptive probe vehicle selection scheme. Moreover, we propose a simple scheme for selecting which vehicles to use as sensors, in order to reduce the communication burden. Numerical simulations demonstrate that %It also demonstrates that it is possible to reduce the communication burden using a triggering mechanism with with this triggering mechanism, the delay is reduced by around $65\%$, compared to a reduction of $72\%$ if all connected vehicles are communicating at all times.

In the thesis, I aim to analyze how people remember their past in changed political circumstances, what and who affect that memory, and why and how does rapture between social memory and historical narratives come about. My subject of inquiry is the personality of Josip Broz Tito and above that the period of socialism and the years of his reign. Studying these my intention is not in writing his biography, rather I use him as an object through which I can get a closer look at the production of a new social memory. I analyze my ethnographic data by using the theory of collective memory and politics of memory theory. Those two main analytical tools are combined with more concepts and hypotheses. The inquiry is done on multisited places, by doing multi-local ethnography namely in Croatia and Serbia. I argue that the mnemonic communities like nations, social groups or power elites influence how people perceive their past and consequently remember historical facts. In times of unstable political circumstances like the change of communist order into capitalistic one, people tend to make sense of their complex past by producing different narratives which are often contested.

Stop-and-go waves on freeways are a well known problem that has typically been addressed using dynamic speed limits. As connected automated vehicles enter the roads, new approaches to traffic control are becoming available, since the control actions can now be communicated to these vehicles directly. It is therefore important to consider automated vehicles independently from the rest of the traffic, using traffic models with multiple vehicle classes. In this paper, we use a multi-class CTM to capture the interaction between the controlled vehicles and the background traffic. Exploiting the nonlinear nature of the model, we are able to first collect enough controlled vehicles into an area, and then use them to actuate the rest of the traffic by acting as a controlled moving bottleneck. In this way, we are able to dissipate stop-and-go waves quicker, improving the throughput and homogenizing the traffic. The effectiveness of the approach is demonstrated in simulations.

In order to achieve the highest possible efficiencies, multi-junction solar cells (MJSC) have to have optimally selected parameters. As very complex devices, it is a demanding task finding the optimal set of parameters. One of possible ways to overcome these difficulties is to use genetic algorithm. In the presented model, number of optimizing parameters is 5M+1 for series constrained M-junctions MJSC. Diffusion dark current, radiative and Auger recombinations are accounted together with ASTMG173–03 Global tilted solar spectra and $\mathrm {k}\cdot \mathrm {p}$ absorption. Efficiencies achieved in case of M = 4 are 50.8% and 55.2% when all losses are taken into account and with only radiative recombination, respectively.

All vessel-type products operating under extreme conditions of temperature, pressure and corrosive environments, such as those in the power, chemical and petrochemical industries, are subjected to intense chemical / structural degradation processes that may lead to cracks. These may propagate in time, causing the product to fail, generating significant economic and material consequences, leading in some cases even to the loss of human lives. The paper presents some effects of the sacrifice layer repairing technique used to restore the geometrical shape by welding of the area from where the flaw material was removed, on the chemical composition.

The continuous development of industrial processes in the petrochemical field requires the use of materials with anticorrosive properties, able to withstand working conditions at high temperatures but also in highly corrosive environments. The basic materials with anticorrosive properties have a high cost price which leads to the need to find alternative manufacturing solutions. In such situations, the use of bimetal plates or the option of welding cladding with an anticorrosive layer of the base material is used. The paper analyses the possibility of strip cladding using the submerged arc welding process of a reactor made of SA 387Gr11Cl.2 basic material, a heat-resistant alloy steel. To achieve the deposition of the appropriate anticorrosive layer (stainless steel type AISI 347) it was necessary to use a buffer layer made of austenitic stainless-steel type 309L. In order to eliminate the internal tensions appeared after the cladding process, the sample was subjected to a stress relieving heat treatment. After the heat treatment, the sample was subjected to non-destructive examinations (visual and penetrant testing) but also to destructive examinations specific to the approval tests of cladding technology (Metallographic tests, Vickers hardness test, bend test, ferrite number, chemical composition). Metallographic tests of cross-sectional phase structures were carried out in macroscopic and microscopic terms. In the area of the deposited material can be observed a typical austenitic casting structure resulting from the use of a high linear energy, specific to the automatic submerged arc welding. Following the performance of hardness measurements made in the characteristic areas of the deposition, it can be seen that there was a slight increase in the values obtained in the heat affected zone, without exceeding the prescribed values for the materials used. Following the analysis of the results obtained from the specific examinations and tests to the plated samples, it can be seen that they are within the limits prescribed by the standards in force regarding the approval of the cladding technology used.

The continuous increase of the requirements regarding the quality of the welded joints (elimination of the influence of the human factor) but also the increase of the productivity of the technological processes imposed the analysis of the possibilities of implementing robotic welding processes. The introduction of robotic production lines is an increasingly common thing in the automotive industry. This paper presents the stages necessary for the realization in welded construction of a crossbeam, part of the chassis of a car. The elaborated welding technology aimed to achieve the transition from semi-mechanized welding of the assembly to robotic welding using the MAG (Metal Activ Gas) welding process. The basic material from which the crossbar is made is S355 MC steel, steel for constructions with high mechanical properties. For the robotic welding of the assembly, the design of the device necessary for the orientation and fixing of the components was made. The welding technology developed was validated by performing standard samples that were subjected to visual examination and penetrant testing but also to destructive examinations which consisted in measuring the hardness in the characteristic points of the welding bead and also by measuring its geometric characteristics. Following the analysis of the initial dimensional values obtained, it resulted that the incorrect positioning of the welding head in relation to the welded components led to the appearance of geometric defects of the welding seams, although the technological parameters of the welding regime were appropriate. After making adjustments on the position of the welding head, accepted characteristics were obtained which led to the decision to validate the welding technology used.

Recipient type products from energetic and chemical industry undergo a wide combined process of corrosion and ware, due to working environment. In order to put this products back in use, in a shorter period of time, welding reconditioning procedures are applied which mainly aim to restore the geometrical configuration but also the characteristics growth. Any welding technology applied, involves melting a filler material but also a part of the base material, mixing them, thereby obtaining the welded joint. The paper present the experimental results obtained in determining the optimal parameters for Metal Active Gas welding deposit that are going to be used for the restoration of some components from energetic and chemical industry and that are highlighting the dependence between the deposit parameters and the chemical composition of the juncture.

Objectives: To investigate the clinical and prognostic significance of absolute basophil count (ABC) in patients with primary myelofibrosis (PMF). Methods: We retrospectively investigated 58 patients with PMF treated in our institution in the period from 2006 to 2017. ABC was obtained in addition to other hematological and clinical parameters. Patients were separated into high and low ABC groups using the Receiver operating characteristic curve analysis. Results: ABC was higher in PMF patients than in healthy controls (P < 0.001). Patients with high ABC had higher white blood cells (P < 0.001), higher red cell distribution width (P = 0.035), higher lactate dehydrogenase (P < 0.001), more frequently had circulatory blasts (P < 0.001), constitutional symptoms (P = 0.030) and massive splenomegaly (P = 0.014). ABC was also positively correlated with absolute monocyte count (AMC) (P < 0.001) and other components of differential blood count. There was no difference in ABC regarding driver mutations or degree of bone marrow fibrosis. Univariately, high ABC was significantly associated with inferior overall survival (hazard ratio (HR) 4.79, P < 0.001). This effect remained statistically significant (HR 4.27, P = 0.009) in a multivariate Cox regression model adjusted for age, gender, Dynamic International Prognostic Scoring System (HR 2.6, P = 0.001) and AMC (HR 8.45, P = 0.002). Discussion: High ABC reflects higher disease activity and stronger proliferative potential of disease. ABC and AMC independently predict survival and therefore seem to reflect different underlying pathophysiologic processes. Hence, both have a potential for improvement of current prognostic scores. Conclusion: Basophils represent a part of malignant clone in PMF and are associated with unfavorable disease features and poor prognosis which is independent of currently established prognostic scoring system and monocytosis.

The aim of the paper is to point out the importance and role of venture capital in creation of new values based on the knowledge economy. By reviewing relevant literature about venture capital, this paper presents the importance of the venture capital investments in innovative activities of SMEs that have an impact on economic growth. Pointing to the importance and quantifying the overall effects of venture capital investments, will be used the overview and trends in venture capital investments in the sectors of economy in Europe which generate a larger number of patents. According to data during the period of 2007 - 2015 will be defined venture capital investments and number of registered patents in the sectors of the knowledge economy. Empirical analysis indicated that the venture investments in the sectors of the knowledge economy generated more patents in those sectors. In addition, the paper analyzes the venture capital investment and innovation activities of SMEs, which are reflected in patent activities, where the result is a correlation between these activities in the European economies.

There is a high number of clinical and biological parameters with impact on prognosis in B-CLL and number of successful prognostic models were developed (clinical stages, CLL IPI, MDACC score, etc.). However, rapidly changing therapeutic landscape with more successful targeted terapines with different modes of action, render most of these models developed in era of chemo and chemoimmunotherapy less useful. Recently simple prognostic score (BALL score) based on 4 parameters (LDH>UNL, B2microglobulin>5mcg/l, Hemoglobin High cost of novel drugs in less affluent countries led to a higher criterion for reimbursement. Until recently in Croatia ibrutinib was reimbursed only for early relapse (less than 24 months from last therapy) or refractory disease with additional criteria for high risk disease including Rai stages III and IV or high tumor burden demonstrated by TTM score >15. TTM score (www.b-cll.org) is old, simple and continuous parameter useful for prognosis and response assessment (Jaksic B et al BJH 1980) and because it cover tumor mass in all major lymphoid compartments and allow tumor distribution assessment (Jaksic O et al, Haematologica 2001) it can be very useful for response assessment to novel agents were redistribution of lymphocytes can be significant (Jaksic O BJH 2014). In other to evaluate usefulness of novel BALL score and old TTM score in real life setting where the novel drug is available only to patients with higher risk defined by respective scores, we have evaluated series of 42 RR CLL patients treated with ibrutinib at our institution since March 2015. There were 15 females and 27 males, median age 70 years (range 53 to 82), 9 patients had 17p deletion, median TTM was 14 (range 1.2-28), 20 patients had Rai stage III/IV. Median follow up was 24 months, and maximal 64 months. Since all patients were in early relapse or refractory, we have actually used simplified BALL score based on only 3 parameters. There was no significant relationship between BALL and TTM in our patient population. In our patient cohort low risk BALL score had only 3 patients, 28 patients had intermediate risk and 11 high risk and it showed only marginal discriminative power (p=0.054) While TTM>15 did not show discriminative power (p=0.14). When we added TTM>18 as an additional parameter (point) to BALL score, this modified score (0-3 low/intermediate - 23 patients and 3-4 high risk - 19 patients) showed significant discriminative power (p=0.002) (Figure 1). Observed results indicate that: 1) performance of prognostic models may be significantly dependent on discriminative power of its components and if these components are criteria for initiation of therapy with novel agent(i.e. only high risk group defined by these parameters) it significantly lower its prognostic power, and vice versa 2) such criteria for therapy selection/initiation until these criteria are met may actually mean that we treat patients with novel agents when these are less effective. We have shown that addition of TTM significantly improves BALL score. Refinement of prognostic scores with parameters that may have predictive power for novel drugs, as well as adaptation criteria for reimbursement in future studies (including pharmacoeconomics) may further improve quality of care of B-CLL patients. Disclosures Jaksic: Roche: Honoraria; Janssen: Honoraria; Abbvie: Honoraria. Pejsa:AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pliva: Honoraria, Membership on an entity's Board of Directors or advisory committees; Alvogen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Oktal Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sandoz: Honoraria, Membership on an entity's Board of Directors or advisory committees.

The advent of connected, automated and autonomous vehicles introduces the possibility for new traffic control approaches. Vehicles equipped with automation and communication systems can be exploited both as sensor and actuators for traffic control actions, thus avoiding the need for new infrastructure. In this paper a multi-class extension of the macroscopic Cell Transmission Model is adopted to describe the interaction between different classes of vehicles, for example human-driven and connected/automated. The vehicle classes are distinguished on the basis of their time headways and their speed. By means of a Model Predictive Control approach, the optimal free-flow speed for the class of connected/automated vehicles is computed and applied to them with the aim of reducing congestion on the highway. The effectiveness of the proposed control law is analyzed depending on the penetration rate of controlled vehicles and the approach is assessed in simulations.

Vehicle platooning has been attracting attention recently because of its ability to improve road capacity, safety and fuel efficiency. Vehicles communicate using Vehicle-to- Vehicle (V2V) wireless communication, making their status (acceleration, position, etc.) available to other vehicles. Shock waves, i.e. zones of reduced traffic speed that propagate upstream, are a well known emergent traffic phenomenon. Since vehicles entering such a zone need to decelerate sharply, shock waves cause a deterioration of fuel economy, driving comfort, and safety. While typically caused by bad driving behavior, recent studies have shown that it is possible to diminish or dissipate shock waves by applying certain good driving behavioral patterns. In this work, we use the information about the traffic situation to adapt the reference speed profile of the platoon we control, in order to mitigate the effect of a shock wave coming from downstream. The platoon leader receives the velocity of the vehicles downstream of the platoon and distance gap between them using V2V communication and it computes the shock wave speed. We show that by doing this we reduce the fuel consumption of the vehicles in the platoon, and improve the traffic situation by helping dissipate the shock wave. We validate our results using microscopic models with the help of a toolchain composed of Matlab, and the SUMO traffic simulator.

Truck platooning, where vehicles drive close together in order to reduce air drag, is a promising technology that is slowly reaching maturity. In order to fully exploit its potential, we will need to be able to efficiently form platoons enroute, while driving on the road, by having the vehicles adjust their speeds so that they catch-up and merge into a platoon. Since this means that the participating vehicles will have to deviate from their own optimal speed profiles, experiencing unpredicted disturbances caused by the surrounding traffic might lead to higher fuel consumption. Therefore, in order to increase the fuel savings and improve their predictability, we devise a control strategy that takes into account the traffic conditions and yields optimal catch-up speeds for both the leader and the follower vehicle. The control strategy is based on minimizing total energy consumption, and it models the vehicles as moving bottlenecks. We compare this strategy to one that does not consider the influence of traffic, and show that it achieves better results in terms of energy savings. QC 20191111

Purpose The purpose of this study is to create the taxonomy of firms based on the nature of the relationship between market-based resources and marketing capabilities. Anchored in the configuration theory, the present study aims to explore simultaneous roles of market-based resources, i.e. customer orientation and competitor orientation, and marketing capabilities, i.e. the execution of marketing practices and activities within a firm, on firm performance. Design/methodology/approach A self-administrated questionnaire was used to collect data from chief executive officers or top managers of 220 firms in Bosnia and Herzegovina, a transitional economy in South Eastern Europe. Findings Drawing on a configuration approach via the latent class analysis, the authors empirically derive four distinct strategic marketing patterns, namely, marketing super achievers, marketing-focused virtuosi, marketing drifters and marketing mass pushers. The findings also highlight how business performance outcomes differ as a function of a class membership. Research limitations/implications Cross-sectional research design and focus on a single country are main limitations of the present study. Thus, longitudinal studies in the context of developed and fast-reforming transition economies are advisable for future work. Practical implications This study enhances the knowledge on how a firm can configure or bundle its market-based resources and marketing capabilities to produce desired outcomes. Findings suggest that joint attention to building market-oriented culture and developing marketing capabilities seems to pay off. However, the authors found that a lack of market knowledge can be substituted by the firms’ ability to build effective promotional and branding capabilities. Thus, the present study adds to the emerging dialog on the relative importance of alternative strategic orientations in achieving superior business performance. Originality/value This study contributes to the strategic marketing literature by examining the synergistic effect of market-based resources and marketing capabilities on firm performance using a configurational approach. It also provides support for the equifinality proposition, suggesting that different “bundles” of market-based resources and marketing capabilities can lead to similar level of performance outcomes.

The paper presents the results obtained following the nondestructive ultrasonic testing of crankpin shaft of a crankshaft that were reconditioned by welding. After the ultrasonic testing, the reconditioned samples were cut and subjected to visual testing and microstructure examination. When the results obtained following the nondestructive tests were analyzed, it was observed that the ultrasonic nondestructive testing method is an efficient way to determine the conformity of the areas that were reconditioned by welding.

The reactions of the base material, during the welding process, consist in chemical composition, volume, structure and granulation changes. There are multiple problems which can occur by welding two steels with totally different chemical composition, i.e. carbon steel S235JR + AR and austenitic stainless X2CrNiMo17-12-2. The process used for making the heterogeneous joint was flux cored arc welding (FCAW), numerically coded 136. The paper presents the effects of welding through heat input, on the structural characterization of welded seam and heat affected zone. It also focuses on the structural characterization of the welded joint obtained using the flux cored wire T 23 12 L P C/M 1, and determining how the base materials participate at the formation of the welding joint.

It’s well known that the professional experience cumulated in years of teaching brings another vision towards certain challenges. The present paper aims to identify the teachers’ difference of opinion regarding certain aspects of satisfaction on all teaching positions – assistant, lecturer, associate professor, professor. The results have been obtained by analyzing 132 answers received after the distribution of a questionnaire regarding satisfaction in technical higher education. After analysis, for the same dimension of satisfaction, a variable distribution could be observed, explained by the different professional experience of each respondent.

The paper presents the authors’ work in identifying the main risks that may arise if pursuing the change of the reconditioning technology through welding the friction liner of the passenger car disc brake based on the technical hazard identification, and the authors analysis and management of these risks by carrying out a risk management system. Theyr work is based on the specifications of the Commission implementing regulation (EU) No 402/2013 on the common safety method for risk evaluation and assessment (EU Regulation 402/2013) [1], which is compulsory for any technical, operational and/or organizational change in the railway field that has an impact on railway safety. Also the purpose is that the modified technology does not affect railway safety. The friction liner from the passenger cars disc brake is a part that ensures the grip of the friction pad, which applies the braking force to the brake disc to realize the braking of the rolling stock. The new reconditioning welding technology can affect the friction liner clamping function, making it possible for the friction pad to fall from the friction liner, resulting in losing braking power on the vehicle, which leads to the occurrence of rail events, thus affecting rail safety.

A Phase I study of A166, a Novel Anti-HER2 Antibody-Drug Conjugate (ADC), in Patients with Locally Advanced/Metastatic Solid Tumors. Purpose: A166 is an Antibody Drug Conjugate (ADC) targeting HER2-expressing cancer cells, aiming for post trastuzumab/TDM1 population and patients with HER2 expressing cancers not commonly treated with trastuzumab and TDM1. The antibody has the same amino acid sequence as trastuzumab, and it is designed to provide uniform distribution of payload molecules, using an innovative antibody-drug linker and duostatin-5 (an MMAF derivative) as payload. This ongoing phase I, open-label, first-in-human study is evaluating the safety, pharmacokinetics (PK), and dose-limiting toxicities (DLT) of A166 to determine the Maximum-Tolerated Dose (MTD) and/or recommended phase II dose (RP2D). Methods: Patients with advance solid tumors received escalating doses of A166 (0.3, 1.2, 3.6, and 4.8 mg/kg), administered intravenously (IV) every three weeks. Patients must have had documented HER2 positivity defined as positive, or amplified on in situ hybridization (ISH) or next-generation sequencing (NGS), or HER2 expression, defined as at least 1+ by validated immunohistochemistry (IHC) test or an activating HER2 mutation. Dose escalations were guided by a Bayesian logistic regression model (BLRM). Assessments include archival tumor molecular status, PK, and efficacy by Response Evaluation Criteria in Solid Tumors (RECIST). Results: 23 subjects [median age 68 (range 50-83), 17 female, 6 male, PS 0-1], have been treated. All patients had metastatic disease: 7 breast, 7 GC/GEJ/EC; 4 CRC, 5 other (lacrimal gland, vulvar, bladder, NSCLC, and ovarian). HER2 expression was available for all 23 patients: 12 (3+), 2 (2+ and amplified), 7 (amplified), 1 (1+), and 1 (HER2 mutated), and most had received previous HER2 targeted therapies (1-7 lines). No significant > Grade 3 AEs at doses below 3.6 mg/kg have been observed. Based on safety and efficacy outcomes, dose levels (DLs) 3.6 and 4.8 mg/kg were expanded to a total of 7 and 8 patients respectively. In these two cohorts, 4 patients experienced grade 2 ophthalmic toxicities involving the ocular surface (3 keratitis, 1 blurred vision), and 2 had Grade 3 keratitis. Treatment was discontinued (n=3) or delayed (n=3), and patients were treated with topical steroids and aggressive lubrication. All patients have resolved/resolving status of the ophthalmic toxicities, with a duration from onset to recovery/improvement of symptoms of 2-3 weeks. Other common drug-related and reversible Grade 1-2 AEs include blurry vision (n=4), peripheral neuropathy (n=3), anemia (n=2), leukopenia (n=2), thrombocytopenia (n=2). No cardiac or liver toxicities have been noted. Preliminary response assessment found that efficacy is evident at DL 3.6 and 4.8 mg/kg. Of 8 evaluable patients at 3.6-4.8 DL, 4/8 had PR, and 6/8 had DCR. Among PRs, 3 had prior anti-HER2 therapies, including 2/3 with prior TDM1. Conclusion: A166 has been well tolerated and shows promising anti-tumor activity in patients with heavily pre-treated HER2-positive cancers. The ophthalmic AEs have been reversible and manageable with supportive management. A detailed regimen for early diagnosis and intervention has been developed to further investigate the management of these toxicities in future cohorts, and three additional dose levels (6.0, 7.2, 8.4 mg/kg) will be added to the escalation phase. Citation Format: Diana M Lopez, Minal Barve, Judy Wang, Andrea J. Bullock, Eirini Pectasides, Ulka Vaishampayan, Alexander I. Spira, Susanna Ulahannan, Amita Patnaik, Rachel E. Sanborn, Dragan Cicic, Qiuqing Ang, Gregory Bergonio, Jordi Rodon Ahnert. A phase I study of A166, a novel anti-HER2 antibody-drug conjugate (ADC), in patients with locally advanced/metastatic solid tumors [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr B005. doi:10.1158/1535-7163.TARG-19-B005

Introduction. Female sex workers (FSWs) are a group at increased risk for human immunodeficiency virus (HIV) infection, and inconsistent condom use with clients is a known risk factor for infection in this group. Objective. The aim of the study was to determine factors associated with inconsistent condom use with clients among female sex workers in Podgorica, Montenegro. Methods. We conducted an HIV bio-behavioral cross-sectional study in a sample of female sex workers recruited by snowball sampling. Results. A total of 142 FSWs were recruited. Eighty-one (57.0%) of them used condoms consistently with clients. HIV prevalence was 0.0%. In the multivariate analysis inconsistent condom use with clients in the previous month was associated with clients? negative personal attitude [age-adjusted odds ratio (AOR) = 22.7, 95% confidence interval (CI) = 2.3-228.0] or client?s indifference (AOR = 13.0, 95% CI = 1.4-118.9) towards using condom during sex with sexual workers, decision making by clients or by mutual agreement with client about using a condom (AOR = 10.2, 95% CI = 3.7-28.0), and early age of first sex (AOR = 5.4, 95% CI = 1.6-18.5). Conclusion. Our results suggest not only the need for further promotion of condom use, information and education for FSW but also the need to strengthen negotiation skills of FSWs with clients on regular use of condoms, as well as the need to extend prevention programs to clients of FSWs.

Background/Aim: We aimed to investigate clinical associations of inflammatory biomarkers neutrophil- tolymphocyte- ratio (NLR) and platelet-to- lymphocyte-ratio (PLR) in patients with myelofibrosis, myeloproliferative neoplasm with inflammatory background. Patients and Methods: We retrospectively analyzed a cohort of 102 myelofibrosis patients. NLR and PLR were assessed in addition to other diseasespecific parameters. Results: NLR and PLR were significantly higher in myelofibrosis than in healthy controls. Higher NLR was significantly associated with Janus-kinase- 2 (JAK2)- mutation, wild-type-Calreticulin (CALR), older age and parameters reflecting increased proliferative potential of disease (higher leukocytes, higher hemoglobin, larger spleensize), whereas there was no significant association with C-reactive-protein (CRP). Higher PLR was significantly associated with absence of blast-phase-disease, absence of constitutional-symptoms, lower percentage-of- circulatoryblasts, smaller spleen-size and lower CRP. In the Coxregression- model, higher- NLR (HR=2.76 ; p=0.004), lower- PLR (HR=1.99 ; p=0.042) and Dynamic- International- Prognostic- System (DIPSS) (HR=3.26 ; p

BACKGROUND: Primary and secondary myelofibrosis (PMF and SMF) are malignant diseases of hematopoietic stem cell characterized by the neoplastic myeloproliferation and a strong inflammatory milieu. The prognostic nutritional index (PNI) integrates information on albumin and absolute lymphocyte count (ALC) and reflects the inflammatory, nutritional and immune status of a patient. The clinical and prognostic significance of albumin, ALC and PNI in patients with myelofibrosis has not been previously investigated. ----- METHODS: We retrospectively analyzed a cohort of 83 myelofibrosis patients treated in our institution from 2006 to 2017. Albumin, ALC and PNI were assessed in addition to other disease specific markers. ----- RESULTS: The PMF and SMF patients had significantly lower ALC and PNI but similar albumin compared to controls. Lower albumin was significantly associated with older age and parameters reflecting more aggressive disease biology (e.g. anemia, lower platelet levels, higher lactate dehydrogenase (LDH), circulatory blasts, transfusion dependency, blast phase disease), inflammation (higher C reactive protein (CRP), constitutional symptoms) and higher degree of bone marrow fibrosis. Lower ALC was significantly associated with lower white blood cells (WBC) and lower circulatory blasts. Low PNI was associated with lower albumin, lower ALC, anemia, lower WBCs, lower serum iron and lower transferrin saturation. There was no difference in albumin, ALC and PNI regarding the driver mutations. In multivariate analysis adjusted for age and gender, low albumin (hazard ratio [HR] = 4.61, P = 0.001), low ALC (HR = 3.54, P = 0.004) and Dynamic International Prognostic Scoring System (DIPSS) (HR = 2.45, P = 0.001) were able to predict inferior survival independently of each other. Accordingly, low PNI (HR = 4.32, P

The advent of automated, infrastructure-controlled vehicles offers new opportunities for traffic control. Even when the number of controlled vehicles is small, they can significantly affect the surrounding traffic. One way of regulating traffic is by using the automated vehicles as controlled moving bottlenecks. We present an extension of the cell transmission model that includes the influence of moving bottlenecks, consistently with the corresponding PDE traffic model. Based on this model, a control strategy is derived for traffic jam resolution. The strategy is tested in simulations, and shown to reduce the average travel time of surrounding vehicles, while also helping dissipate the traffic jam faster and ensuring the controlled vehicle avoids it. QC 20190304

Background/Aim: We aimed to investigate clinical associations of inflammatory biomarkers neutrophil-tolymphocyte- ratio (NLR) and platelet-to-lymphocyte-ratio (PLR) in patients with myelofibrosis, myeloproliferative neoplasm with inflammatory background. Patients and Methods: We retrospectively analyzed a cohort of 102 myelofibrosis patients. NLR and PLR were assessed in addition to other diseasespecific parameters. Results: NLR and PLR were significantly higher in myelofibrosis than in healthy controls. Higher NLR was significantly associated with Janus-kinase-2 (JAK2)- mutation, wild-type-Calreticulin (CALR), older age and parameters reflecting increased proliferative potential of disease (higher leukocytes, higher hemoglobin, larger spleensize), whereas there was no significant association with C-reactive-protein (CRP). Higher PLR was significantly associated with absence of blast-phase-disease, absence of constitutional-symptoms, lower percentage-of- circulatoryblasts, smaller spleen-size and lower CRP. In the Coxregression- model, higher-NLR (HR=2.76 ; p=0.004), lower- PLR (HR=1.99 ; p=0.042) and Dynamic-International