Okay, so welcome everyone to this webinar, which we hold in order to replace the previous one which had to be cancelled, and I'm very happy to see that many of you returned to this one. And we will listen to Dr. Maria Victoria Mateos, who will speak about the or given overview of the most important data from the field of multiple myeloma, with special regard to the Ash Conference in San Diego. And well, you take it away Dr. Mateos, and we are looking forward to what you've got to tell us. Okay, thank you and good afternoon everyone. First, so thanks to the myeloma patients in Europe for giving me the opportunity to be here with you today, sharing an overview of recent data and updates from Ash in multiple myeloma, and as Thomas mentioned, Ash meeting took place in San Diego in December. Next slide, you can see here like at last American Society of Matology meeting, so almost 1000 abstracts based on multiple myeloma was submitted to this Congress. In fact, the massive number of oral and postures were based on CAR T cells, many important novel updates. And, well, we had the opportunity to listen a new late breaking abstract in which so we are going to have the opportunity to see how a new standard of care for newly diagnosed on myeloma patients, non-eligible for otological systems of transplantation, will be submitted very soon to be approved by the authorities around the world. Next slide. First I will do just so one introduction about the general concepts and we will discuss later on the novel data we have coming from newly diagnosed to myeloma patients and the last part of the presentation will be focused on relax and refractory myeloma patients before to have some minutes for discussion with you. Next slide. Next slide, general concepts. So myeloma maybe you have heard many times that myeloma remains today as some incurable disease. And I decided to start with this slide that was not basically presented at us, but recently published in Black Council Journal and is an international myeloma working group analysis in which you can see here like approximately 15% of myeloma patients can be potentially cured. Next slide. If we wanted to try to identify the patients potentially curable with multiple myeloma, you can see like the age, the thrombocytes level, the novel agents based induction, the maintenance therapy, but the very important the achievement of complete response after a total of extensive transplantation. In other words, the quality of the response is becoming an important surrogate market predicting progress from free survival, but also overall survival and at the end, long-term survivors. Next slide. Let's move on now to focus on newly diagnosed myeloma patients and the next slide. You can see here the standard approach for the management of a newly diagnosed myeloma patients transplant eligible and transplant eligible. You know that the means usually patients younger than 65 or even younger than 70, even the comorbidities are not present and if the performance status is good and the general approach includes according to the ESMO as well as NCSN guidelines, induction, transplant and maintenance. What about the next slide induction? You have to know that in terms of induction before autologous extensive transplantation, all patients should receive it today a free drug-based combination and during this meeting we had the opportunity to see an update about the Bortezomibylinolidomide and hexamedazone VRD data. So you have to know that this combination will be approved by FDA and also in Europe of maybe very soon. When we evaluated the outcome of this combination VRD in young newly diagnosed myeloma patients, the median progression of the survival is of approximately 50 months with a median overall survival that has not been reached yet in patients younger than 65. But in addition to this study, the Spanish myeloma group evaluated also the role of Bortezomibylinolidomide and hexamedazone in a series of almost 500 newly diagnosed myeloma patients compared in this integrated analysis presented at us meeting with the VTD, Bortezomibylinolidomide and hexamedazone. Next slide briefly, you can see like VRD, Bortezomibylinolidomide and hexamedazone is slightly superior to Bortezomibylinolidomide and hexamedazone. In terms of BGPR rate or better, post-induction as well as post-transplant, most importantly the proportion of patients achieving and detectable minimal residual disease after induction and transplant are also slightly higher in comparison with VTD. But you have also to know that the main advantage of VRD versus VTD is derived from the toxicity profile because of the use of lenolidomide, Bortezomibylinolidomide and hexamedazone induced a very low rate of peripheral neuropathy that, as you probably know, is the main adverse event related to the administration of lenolidomide. So in conclusion, these results are further supported by the use of Bortezomibylinolidomide and hexamedazone as the control arm in many ongoing randomized controlled clinical trials. Next slide. New combinations about induction regimen, RDD is going to be the new standard of care, but during our meeting we had the opportunity to see new combinations that are coming. Next slide. The first one is to replace Bortezomibylinolidomide by carfilzomib and carfilzomib in combination with cyclophosphamide and hexamedazone followed by transplant and consolidation with carfilzomibylinolidomide and cyclophosphamide and hexamedazone was compared with carfilzomibylinolidomide and hexamedazone followed or not by autologous transfer transplantation. The next slide, the main message from this presentation is that after induction, after four cycles of induction, carfilzomib in combination with lenolidomide and hexamedazone is superior to carfilzomibylinolidomide and hexamedazone. In the next slide, when we evaluate the overall response rate, the VGPR rate or better, as well as the minimum residual disease negative rate that you can see in blue, carfilzomibylinolidomide and hexamedazone is always superior to carfilzomibycyclophosphamide and hexamedazone. We have to wait to have a long-term follow-up in order to see the final outcome of these patients because, in fact, in this study, you can see here like a supergroup of patients received KERD transplant following by KERD and a supergroup of patients received just KERD 12 cycles without autologous transfer transplantation and the overall response rate was similar. So we have to wait to know how the outcomes of this patient are and we will have these results in the upcoming Congress. But KERD can be in the future another new standard of care to be used as induction maybe before autologous transfer transplantation. In the next slide, another possible combination that we will have in the future are carfilzomibylinolidomide and hexamedazone plus the monoclonal antibody that I do not have. So this combination has been just evaluated in a small series of patients only 16. But in the next slide, you can see like this combination is safer for the patients and the addition of data to MAP to VRD does not result in any safety signal. And in the next slide, you can see like a preliminary overall response rate as well as complete response rate is promising and as well as the minimum residual disease negative rate that reaches 50% at the end of consolidation. Another combination in the next slide also evaluated in a small series of patients is bortesomibycyclofosomide hexamedazone plus the data to MAP. And again, I would give you the same message. So this combination will be maybe a new standard of care in the future because in the next slide, you can see like from the safety point of view, there are not major concerns. And in the next slide, when we evaluated the efficacy, you can see here like after four induction cycles, the overall response rate is of approximately 80% with a significant proportion of patients achieving VGPR rate or better. In the next slide, you can see preliminary progression for survival and overall survival data, but I am not going to focus. Just one second. Am I on the right slide now, or is this the next one that you that you want that you are talking about this one? I am going to, I am talking about right now in the Kumar slide, hexazomibycyclofosomide hexamedazone. Do you see the slide? Data plus hexazomibycyclofosomide hexamedazone in newly diagnosed myeloma patients phase two study. I am trying to find this. Well, I can say which is the slide number 24. Slide number 24. Here we are. Yes. Yeah. Okay. This is just another example of a new combination that maybe can represent a new standard of care. X-azomib, as you know, is a proteasome inhibitor of oral administration and was in this study combined with the lenalidomide and the hexamedazone in combination with the CD38 monoclonal antibody garatumumab. Only 38 patients. Next slide. You can see here like this combination is effective and in fact, so the best response rate was almost 100%, meaning that almost all patients responded with approximately 20% of them in complete response. You have to know that all these studies I am showing you right now are preliminary studies conducted in small cities of patients, but they can be the rationale for moving towards large phase three randomized trials resulting at the end in new combinations, new standard of care to be used in the upfront setting. Next slide. You can see here again this general approach for the management of myeloma in the transplant candidate newly diagnosed patient induction and we have just reviewed the induction transplant followed by maintenance. What is the role of otologous stencil transplantation after induction with the novel agent spatial combinations? In the next slide, you can see the outcome reported by the Spanish myeloma group in a study conducted more than 10 years ago and why this study is important because patients were included in this study and received in blue as you can see proteasome and phalidomide and hexamedazone more than 10 years ago and we can see here like now approximately 25% of the patients remain alive and free of progression. One out of four patients included in this study receiving VTD remained without progression and when we evaluated the overall survival more than 50% of the patients remain alive after 10 years of follow-up and these results have been confirmed also by the Italian myeloma group and this so show a clear message that I would like to share with you the survival of patients with multiple myeloma is significantly improving. In the next slide, you can see here a meta-analysis presented by Michele Cabo from Bologna in Italy putting together data from patients included in three large European studies. In all these studies, patients received induction with proteasome, phalidomide and hexamedazone and approximately half of the patients received single otologous stencil transplantation and half of the patients received double otologous stencil transplantation. In the next slide, the message is that well tandem otologous stencil transplantation so double otologous stencil transplantation is better than single transplant in the intent to treat patient population in the overall population but what is important to note and this is a clear message to put in practice is that the patients with high risk cytogenetic abnormalities or patients with high risk features benefited the most from double otologous stencil transplantation and this is what physicians in Europe are mostly doing in their clinical practice tandem otologous stencil transplantation for patients with high risk cytogenetic abnormalities. The next slide following the general approach for the treatment of young newly diagnosed myeloma patients what about the maintenance and in the next slide you can see like at ARS meeting a new trial was presented evaluating hexasome with the oral proteasome inhibitor as part of maintenance therapy and compared in this case with placebo. You have to know that hexasome was given in this trial only during two years and this study met its primary endpoint and the use of hexasome resulted into a significant benefit in terms of progression of survival versus placebo and in fact the tolerability of hexasome as maintenance is excellent because the frequency of hematological and non-hematological adverse events were really very low so maybe hexasome can be potentially used as maintenance in the future if this drug is approved by the authorities you have to know that although the study met its primary endpoint it stood out the benefit so it's not very evident and in fact the use of hexasome resulted in a median progression for survival of approximate 27 months versus 21 months for patients in the placebo arm. In which situation we can potentially select hexasome to be used as maintenance versus lenalidomide that as you know is the standard of care to be used as maintenance maybe in patients in which lenalidomide can't be given due to poor tolerance or maybe in patients with high risk cytogenetical normalities in which we know that the role of proteasome inhibitor is important and the next step maybe is to combine hexasome in combination with lenalidomide especially in patients with high risk cytogenetical normalities. The next slide you can see here a summary of what we have heard at our meeting regarding the newly diagnosed myeloma patients transplantal eligible VRDS induction the newest standard of care novel combos KERD and maybe this three drug based combination plus the retinoma transplant and concerning maintenance len as a standard of care lenalidomide and hexasome as the new oral proteasome inhibitor anything new in the next slide you can see here like the CAR T cells that as I previously said many oral presentations were based on CAR T cells and one of these presentation was based on the use of CAR T cells in the upfront setting only 10 patients in a Chinese center with high risk that these 10 patients received a CAR T targeting CD19 and BCMA after otolosis and cell transplantation. In the next slide you can see if we focus on the last column the latest response in the purple you can see how 50 percent of patients achieved a stringent complete response 20 percent complete response 30 percent of VGPR and in fact at the bottom of the slide we can see how 60 percent of patients achieved undetectable minima residual disease this is just something very preliminary but of course very promising and maybe we have to move towards the use of these new immunotherapy strategies like CAR T cells maybe in the upfront setting but in patients with high risk. Next slide let's now briefly to evaluate the latest news presented at Ash meeting but based on the transplant in a eligible patient and well we have right now two new possibilities that were presented and updated at Ash meeting the first one is based on a VMP VMP plus data to MoMAB this combination was presented the one year ago and published in New England Journal of Medicine and in fact VMP plus data to MoMAB you probably know that was approved by both FDA and European Medicine Agency and during this Ash meeting we had the opportunity to see an update in the next slide you can see the design of the action study in which VMP was compared with VMP plus data to MoMAB nine cycles followed by data to MoMAB maintenance signal agent in the next slide baseline characteristics of the patients that I am not going to focus on that in the next slide this is a characteristics again I am not going to focus next slide this slide is important and you can see the progression of free survival updated the median follow-up now is 28 months and you can see like there is a big difference between data VMP versus VMP and in fact so the addition of data to MoMAB to VMP resulted into a significant benefit in terms of progression free survival in the next slide you can see like the progression of the survival benefit that was observed across the different two group of patients and in the next slide you can see like the addition of data to MoMAB to VOTES or even Melfalan and Porenison resulted in an overall response rate of 91 percent this means for your information that almost all elderly newly diagnosed myeloma patients who received data plus VMP respond and are able to achieve at least partial response but what is much more relevant is that approximately half of them 45 percent of them achieved complete response and in the next slide you can see how in addition approximately one third of the patients 27 percent achieved minimal residual disease negative and when we evaluate how the progression free survival is when patients achieve the minimal residual disease negative you can see like there is a big difference and the progression free survival is much more longer in the next slide you can see here the evaluation of a surrogate marker for overall survival if this is progression free survival 2 and in the next slide you can see the progression free survival curve that it is representing the curve that we will see when the overall survival data are mature and you can see here like there is already a significant benefit in terms of progression free survival 2 and the benefit in overall survival will be present but we need longer follow up in the next slide important data safety profile safety profile for the patients I would say the first and when we continue with the data to map a single agent beyond the cycle number nine you can see here like the frequency of grade three four adverse event is really very very low and no more than two or three patients develop the respiratory infections back pain or influenza indicating that the tolerability of data to mapping this case in combination with VMP is very good in the next slide so you can see here again the general slide in which so we are going to evaluate another new combinations that we can potentially use in the elderly population lindex plus a vortex or lindex plus data to mumaba lindex plus data to mumaba has been maybe the most important abstract presented at ash meeting and in fact this was presented in the late break in abstract session so an special session in which so the scientific committee select the six most relevant abstracts presented at the congress in this study the nadidomide and examedason was compared with data to mumaba lenidomide and examedason again in the elderly population in the next slide you can see the baseline demographic and clinical characteristics and i am not going to focus on the baseline characteristics in the next slide patient disposition but i think that it's not relevant for your information but in the next slide treatment exposure is not relevant for you but in the next slide you can see the progression for survival and this is important because of the median follow-up is 28 months and again you can see here like the addition of data to mumaba to lenidomide and examedason resulted into a significant benefit in terms of progression for survival and in fact the control arm you have to know that it was very good because lenidomide and examedason has continued therapy resulted in a median progression for survival over 32 months but when we add data to mumaba the benefit is much more evident in the next slide progression for survival benefit across the different subgroup of patients in the next slide again the overall response rate and the overall response rate the complete response rate and minimum residual disease negative rate are similar to that previously reported for data plus vmp 93% of overall response rate 48% of complete response rate and 24% of minimal residual disease negative rate so these results are very good results and in the next slide you can see how patients who achieved minimal residual disease negative have a significant benefit in terms of progression for survival in the next slide the overall survival for preliminary data but again we can see a trend to see a benefit in terms of overall survival for the three combination for the three drug-based combination data to mumaba lenidomide and examedason in the next slide a safety profile acceptable with no menu-matological or non-ematological adverse events and a safety profile consistent with the safety profile i previously said for data plus vmp in the alzion study in the next slide we can see here again the trial in which the bortezomible lenidomide and examedason was compared with lenidomide and examedason alone and in this situation and in this study in the next slide we are going to focus on the elderly population older than 65 or even older than 75 and this combination can represent also a new standard of care for the elderly population because the median progression for survival is approximately three years and the overall survival is over five years so vrd represents also a potential standard of care for this combination in the next slide i think that you can see here the three new standards of care for newly diagnosed myeloma patients non-aligible for otologous dental transplantation data vmp data lenidomide and examedason and bortezomible lenidomide and examedason fda and european medicine agency have approved only data vmp but the other two regimes will be approved in the upcoming months maybe before the end of this year in the next slide just to mention that other combinations that we can potentially have for this patient population and were presented during our meeting lenidomide and examedason as continuous therapy so maybe you know that this is a concept lenidomide and examedason is usually given to our patients as continuous therapy and the lenidomide is hold on doctor just one just one second is this the slide which says management of multiple myeloma in the non-transplant candidate no next slide no the next slide all right thank you so i was saying that the lenidomide and examedason is usually given to our patients as continuous therapy and lenidomide is usually given at the dose of 25 milligrams 20 days followed by one week rest in combination with the examedason 40 or 20 milligrams weekly over in this study what the italian myeloma group did was to compare this conventional standard of care with lendex induction nine cycles full doses followed by lenidomide single agent at low dose only 10 milligrams without the examedason why this study is very important from the patient point of view because the examedason as continuous therapy can influence the quality of life of the patients and can result into the development of significant hematological and non-hematological adverse events so in the next slide we can see how when we did when we give it to our patients lendex followed by lenidomide as continuous therapy the outcome of the patient is better but why the outcome is better because the toxicity profile is better and the incidence of adverse event is inferior so from the practical point of view maybe all physicians treating elderly patients with myeloma after an induction with a lendex full dose it is possible to eliminate the examedason and to continue with the lenidomide at a reduced dose we are going to have the same benefit in terms of overall response rate complete response rate progression for survival but we are going to significantly improve the tolerability what is relevant for the elderly population in the next slide so why i'm going to show you briefly new combinations xasomibidata tumumab and examedason the oral propeasome inhibitor plus the monoclonal antibody and this combination was evaluated in a specific population and fit and frail patients in the next slide just preliminary results because the number of patients is very small only 20 patients but while this combination was effective and especially was safe with a few patients discontinuing the trial due to toxicity in the next slide another possibility is to combine bortesomibel lenidomide and examedason i previously said that this is going to be a new standard of for this combination plus isatuximab and you have to know isatuximab because it's another cd30h monoclonal antibody like daratumumab but daratumumab is already approved and isatuximab is not yet approved but in the next slide you can see how the addition of this monoclonal antibody isatuximab to RVD is effective in this elderly population with a significant proportion of patients achieving at least vgpr and in fact a significant proportion of patients achieved in fact the minimal residual disease negative so these results are very positive and in the next slide as 2018 and let's go to focus now on relapse and refractory myeloma patients and in the next slide you can see here four cardinal points that all physicians have to consider when we have in front of us a relapse and refractory myeloma patients and we have to evaluate the type of relapse the efficacy of previous therapies the toxicity the further options and of course we have also to include the patients preferences the convenience of administration and why not the cost and in the next slide you can see the esmo guidelines 2017 published a couple of years ago and this is the guidelines that most physicians in europe are following right now in order to rescue our patients with multiple myeloma in the next slide is again the same slide in a different format just to mention something important that you have to know the treatment that given as part of the first line of therapy is clearly to influence the treatment that we are going to select at the moment of relapse and this is becoming something very important we have to try to give always the best the first but the first line of therapy is going to influence the second line of therapy in the next slide you can see how patients treated with the bortesomy the basic combinations in the first line exposed or not to leanally the mind but no progressing under leanally the mind therapy so patients non refractory to leanally the mind at the moment of first relapse these patients are usually rescued by carfil so maybe leanally the mind and the exam medicine that are too mobile and a little mind and the exam medicine and it's true that it is possible also to use xasome level and a little mind and the exam medicine or ill or too sum up leanally the mind and the exam medicine during this as congress in the next slide we had the opportunity to see the update of the combination based on data to map leanally the mind and the exam medicine and at the relaxer it is very important to note that the median progression for survival was 44.5 months this median progression for survival is the longest one reported in the relapse setting in a phase three clinical trial and in the next slide we can see how if we add data to move up to leanally the mind and the exam medicine in the relapse setting the overall response rate is 93% and the complete response rate 57% with 30% of minima residual disease negative in the next slide while the outcome for patients receiving data to move up and next in the first relapse and the outcome is better as well as if the patients achieve the complete response the progression for survival is much more longer and there is a benefit in terms of progression for survival too that I previously said that this is a surrogate market for overall survival in the next slide you can see the benefit of data in combination with lentex for patients with high risk cytogenetic abnormalities and this combination is effective in this population and it can represent an option for patients with high risk feature. In the next slide you can see here the evaluation of sustained minima residual disease this is and maybe you have to know that this is a new response criteria published a couple of years ago by the international myeloma working group sustained minima residual disease negativity means that we evaluated today the minima residual disease is negative and we evaluated the MRD again one year later and if the minima residual disease is negative again we can say that this patient is in sustained minima residual disease negative and when we evaluate how the outcome is for these patients with sustained minima residual disease negative you can see like the progression for survival cure is a flat because 100% of patients remain alive and free of donation and this has been evaluated in the pollux study receiving lenalidomide dexamethasone plus data to the mother. In the next slide we can see another possibility patients treated in the first line of therapy with both testimony based combination and exposed to lenalidomide and progressing under lenalidomide therapy so these patients would be I would say lenalidomide refractory. How are we going to rescue to these patients? In the next slide we are going to see how the combinations that we usually select for this for this population are carfil somiband dexamethasone or data to move up in combination with vortex somiband dexamethasone and we can select one or another based on patients preferences patients characteristics as well as disease characteristics. In the next slide during this meeting I had the opportunity to present the update of the use of data in patients receiving this combination in first relapse and when this patient received the data at first relapse the median progression for survival was 27 months and this efficacy was maintained in spite of prior therapy with either vortex somib or lenalidomide what is important and in the next slide you can see this curve data reading after vortex somib and after lenalidomide and in the next slide similar efficacy results you will select the use of carfil somib and dexamethasone as part of the first relapse. In the next slide you can see the outcome of data of the somib and dexamethasone in patients with high recital genetic abnormalities that it's good and it is possible to use this combination. In the next slide again the evaluation of the sustained the minimal recital disease negativity after data vortex somib and dexamethasone and this is also an excellent surrogate marker for progression of the survival as well as also overall survival. In the next slide so this is you can see in gray different boxer different boxes with new combinations new combinations that are going to be used the more and more in first relapses. During this as congress we had the opportunity to see efficacy and safety results from some of these combinations but you have to know that most of them were phase one two clinical trials so the results are not much yet and we need to have the results of phase three randomized clinical trials. In the next slide this is a BC slide that I am not going to focus on that but in the next slide this is a comparison also about the lennaridoma refractory patients. Let's go to move to the next slide and well this is just to summarize that maybe today for patients refractory to lennaridomaid as I previously said we have to rescue these patients with carfil somib dexamethasone or vortex somib dexamethasone plus datatumumab but in the near future new options are coming and these combinations will be pomalidomide vortex somib and dexamethasone, pomalidomide cyclophosphamide and dexamethasone, pomalidomide hexamethasone datatumumab, pomalidomide hexamethasone plus carfil somib or maybe carfil somib dexamethasone plus datatumumab and what about subsequent relapses so patients in third line and beyond do we have new agents to rescue these patients the answer is yes in the next slide you can see in the bottom how new agents pomdex plus something else monoclonal antibodies and novel agents are going to be evaluated in this specific population in the next slide you can see again isatuximabas monotherapy the cd38 monoclonal antibody similar to datatumumab and in the next slide you can see an important message also from the practical point of view when the monoclonal antibody is combined with dexamethasone the overall response rate and the progression for survival duplicated in comparison with the use of the monoclonal antibody as single agent so in the clinical practice maybe if we decided to use the monoclonal antibody as single agent a good option is to add dexamethasone because we are not going to increase the toxicity and we are going to increase the efficacy in the next slide you can see here melphlufen melphlufen is a novel targeted alkylating peptide you have heard about melphalan but melphlufen is not like melphalan it's a new alkylator with different properties and it is much more selective just for the myeloma cells inducing myeloma directed cytotoxicity avoiding off target effects melphlufen in the next slide was evaluated in a series of heavily protruded myeloma patients all of them refractory to datatumumab and refractory to pomalidomide and in this situation the combination is effective the combination is also safe and there are many clinical trials currently ongoing evaluating the role of melphlufen in different settings of patients with multiple myeloma in the next slide you can see selenexor selenexor is also a novel agent that will be maybe very soon approved by our authorities and was evaluated in combination with dexamethasone in pental refractory myeloma patients so patients that have been previously exposed to all conventional regimes and in the next slide we can see here like this combination is effective in terms of overall response rate progression for survival and overall survival with a good safety profile selenexor has to be all has to be always combined with dexamethasone in order to ameliorate some gastrointestinal toxicity but it is acceptable and I repeated this combination will be approved soon by our authorities and selenexor in the next slide has been also combined with datatumumab and dexamethasone in relapsed and refractory myeloma patients and in the next slide you can see like this combination is effective and this is the message I would like to share with you and selenexor is going to be combined with dexamethasone myeloma and also with datatumumab in the next slide so let's go to focus in the last five minutes of my presentation in the immune therapies immune therapy and you can see here in red passive immunotherapy and especially adoptive therapy and cell therapies or new monoclonal antibodies and during the US meeting in the next slide we had the opportunity to see the preliminary results of a new agent that is AMG420 or 420 is an anti-BCMA bite this monoclonal antibody you can see here in this picture like it's a molecule that it is going to target the plasma cell because the plasma cell in the right part of the slide you can see like a BCMA is expressed on the surface of the plasma cells what is the peculiarity of this specific type of monoclonal antibody that this monoclonal antibody in the pink targets the BCMA expressed on the surface of the plasma cells but this bite this monoclonal antibody bring with him the T lymphocyte and you know that the T lymphocyte is the cells that are going to attack and to destroy and to engulf our myeloma cells so it is not necessary that the T lymphocyte arrives to the bone marrow to destroy the plasma cells because these cells are going to be engaged with the monoclonal antibody so these specific type of monoclonal antibodies are very attractive and in the next slide you can see here like this was a phase one study first in human so this is a dose escalation study in which patients started to receive a very low dose of this monoclonal antibody and the important message is that when we evaluated the overall response rate and the efficacy in patients who received the maximum tolerated dose that was 400 micrograms per day in the next slide we can see like these patients and you can see here in the table they are in complete response partial response complete response minimal this is negative minimal this is negative so very encouraging efficacy results we have to take care about the toxicity from my point of view especially infections because some severe infections were reported but this is something completely new that maybe will be improved for sure and while this new monoclonal antibody is going to be expanded and new clinical priors are going to be activated in many European centers and in the next slide we are going to see the results coming from a CAR-T so in the last in the in the last slide you can see how there were two oral sessions in which all presentations were based on CAR-T cells but I decided to show you this because this is new this is a CAR-T targeting again BCMA expressed on the surface of the plasma cells evaluated in China in an unique institution in 57 patients where these patient populations were relapsing on refractory myeloma patients but you have to know that relapsing on refractory myeloma patients in China and this means that these patients have been previously exposed to bortesomib and lenalidomide but these patients have not been previously exposed to data to mumab because in China data to mumab is very expensive it's cheaper for them to have access to a CAR-T than to data to mumab and this is the rational and this is the reason why in China there are so many CAR-Ts in the next slide you can see the overall response rate for these 57 patients included in this study 88% but 74% achieved the complete response and the minimum residual disease negative was negative in 68% of the patients so these responses this overall response rate and complete response rate were really very relevant and in fact the responses were maintained regardless the dose of these cells infused as well as the BCMA expressed on the expression on the surface of the plasma cells in the next slide you can see the progression for survival so CAR-Ts in myeloma are not curative at least at this moment in which we are including in these studies relapsing on refractory myeloma patients the median progression for survival is 15 months and in the next slide we can see here the same progression for survival curve looking how when the patients achieved minimal residual disease negative the progression for survival was longer of approximately two years in the next slide the overall survival median not reached for these patients and when we focus on patients who achieved minimal residual disease negative so at two years 94% of the patients remain alive so these results are again encouraging but well we have to evaluate the more and more these CAR-Ts not only in heavily perpetuated myeloma patients but maybe at earlier stages of the disease in order to see if this strategy can be a potential curative option for myeloma patients. In the next slide this is the list I previously said two oral sessions for immunotherapists including CAR-T and by specific diesel-engaged monoclonal antibodies but well a long list of abstracts based on CAR-T cells with a clear message promising efficacy and safety results but we need a way to have a longer follow-up and to have more and more data and so I stop here and we have at least seven or eight minutes if you want for discussions or questions thank you very much thank you thank you doctor a lot are there any questions or comments from from the audience please indicate perhaps in the chat box and then I can unmute you or you can also raise your hand by pressing the hand button on your control panel which will then indicate here that you would like to speak if you have any questions or comments well it seems that nobody has any questions or comments so I would like to thank you once again for this for this very comprehensive presentation which will then be also I mean the recording of this webinar will also be shared with the wider community and in case you have any subsequent questions or comments to make then of course you're very welcome to write to us at my Alma patients Europe especially to Anava Yeho or even myself my name is Tamar Gretzky so once again thank you very much for the presentation and thank you very much for attending and with this I will say goodbye for today and talk to you again


So we're here at Atmel, and who are you? So, hi, I'm Eric, so I'm with the Qters Perk Monkey Team based out of Norway. So, this is the main reason I'm here. Atmel just recently introduced the lowest power captive touch surface. This is based on the Atmel smart controllers, this is the SAM D20. It has the peripheral touch controller, which is the hardware engine that enables this touch surface. So the key point here is, it's really ultra low power. It works down to four micramps, wake up on touch for four micramps, and also it supports dual touch, so you can do two touches. And if you see here, you can see the X and Y position and the area. You can also have a touch reporter where it shows where your finger is. So, four micramps, how low is that? It's really really low. Are you saying that the touch can be always enabled and then waiting for you to touch it? Yeah, then it runs out to four micramps until you touch it, it wakes up, does the acquisition and then finds out what it needs to do and then goes back to sleep. So you don't need a power button? No. It just stays and waits? Yeah. And then when you touch it, how high does it go? Oh, it depends on your application. It's typically maybe 150 to 200 micramps, but it really depends on your application. So has it compared to other solutions from before? From Atmo? From anyone. So, for Atmo, this is the first time you're doing touch surface on a microcontroller. And this is the key selling point here. In average, it's consuming around 10% of the CPU power, which means you have 90% out of the core to do whatever you want to do. So, 90% for what? Yeah, you can do it to a maintenance controller or you can do any type of control, LEDs or communication, anything. So this is the way Atmo would do touch? Yeah. And it's by doing it much lower power than everybody else? Yeah, this is the lowest power. So I think the closest is like around 12 micramps. So it's three times the battery lifetime. So if you have a tablet with this, how long does it last before? Well, the tablet then you need to go for the Max Touch, the bigger high-end version of the touch controllers you have. This is more for remote controls, PC mouse, gaming, or wearables like health bands, fitness bands, or GPS trackers, sport watches, these things. So you can have this on a smartwatch kind of device? Yeah. And it lasts for a long time on a smartwatch? Yeah, sure. Like not decades? No, it depends. Let me put it this way. It's not the touch that's going to drain the battery. It's the other part, so yeah.


Today I'm here to present some tips in Magento development which will be very helpful for developers I think. So we can start from here, like what are the best practices we can follow in Magento to get it better and better output from Magento in our website to make it more powerful. So here is the agenda of my presentation is first week I can introduce like why we need to do this best, why we need to follow all these best practices in Magento after that I can share some best practices in which I can compare what is the wrong we are doing and what is the correct way we can do and after that we can conclude some points. So in interaction like I can say Magento experts consultancy group ECG which is known as ECG has conducted many code audits for their clients and they find some coding issues that's why their stores are very taking high loads and so from about 28% of the issues affected performance and scalability of the code and the top 5 performance coding issues represent 84% of the performing issues. So most of the issues are related to insufficient operations redundant or useless computations and memory misuses. So among 5 these these are the calculating the size of an array on each iteration of a loop. So whenever we use a forage loop so at the time we calculate the size of the array. So I can explain all these point in the further slides and after that the SQL queries inside a loop loading the same module multiple times redundant data set utilization insufficient memory utilizations. So these are the major findings by the Magento itself. So these are the yeah you can say it's this PPD is given from Magento from Magento also. So here first is the calculating the size of the array in on each iteration of a loop. So here you can see like if we use a count in for a statement then it is calculating every time as my loop rotates. So what is the good practices we have to calculate the counts at the first and then just use the variable in the forage iteration. So it will be very fast and after that SQL query inside a loop we can say like in Magento's we can load models in to get data like it's an example like if I need to get a product data then I need to load my model which is actually hitting the database. So here you can see for in forage loop I have multiple number of IDs and I am in each iteration I am hitting the database to calling the models. So instead of this we have to calculate our model outside the loop and then just iterate the collection. Collection will contain all the data of these product IDs which I have passed here. So this is the best practice we can use here and after that the loading the same model multiple times like I have to show some SKU my product SKU and my product attributes like color size I have to show on front end then what I can but usually we prefer is we can load the model then get the attribute from that product and again if I need to get the SKU of that product then I can again load it but it will very time consuming. So we have to follow like we have to only load model only once and from that model we are already getting all the data. So whatever we have to show we just have to retrieve from that data instead of loading the same products many times or sometimes we no need to load the whole models like in Magento on front end we have to show only color I don't need of size and different SKU names and different things so I can just directly load the SKU or the size by ID of the product. So this will only give me the SKU. So after that the memory fetching large results sets in Magento or we can say it's a normal PHP in which we just get fetch all the results like I have in my tables I have a one lack of records if I will fetch once it will be a my memory usage actually. So it will be a good to calculate a row by row in a loop in a while loop I need to fetch actually one row and then process it then one row then process it instead of getting all whole data which will be a memory actually and after that query resulting limitations we can say in Magento whenever we fetch data we don't use generally limits like I have to fetch a user information in which I just already mentioned in model like particular user data but instead of not defining the size or the limit I am fetching the whole data or accessing the whole database to get that particular information instead of this if I will apply some limit or something like in the collection you can use get limit or set limit something after that we can also use get size instead of get count instead of counts the difference is here count will we can say scan all the database to get the count every time and the get size will just give you directly the size of the collection which you have that so or overriding the core file actually very often developers rewrite the core files when there is a possible way to accomplish the functionality by the observer Magento have very useful feature and very beautiful feature which is an event observers so instead of rewriting the core modules in Magento we have to use the events like whenever any user add the product into the cart then we don't we have to add or restrict some condition there then we then we don't need to modify the core code in Magento we already have an event like add to cart after or add to cart before so at that particular point you can write the code Magento will do their functionality without writing the rewrite core files actually so these are the some basic best practices in Magento's all are not of Magento are some of from PHP also but we generally use this all in Magento as the Magento is built in PHP and following the Zend framework so we have to follow all this and also you can whenever we have to debug anything in Magento we have to use the locks instead of for like eco exit in like we did every time in PHP we write some print R or some using the eco exit to check the execution of the code so instead of doing this we can use the locks in the locks we can store whatever the flow of our code so it will not affect the end user also it will be very useful when we are debugging on the production site actually in production we cannot just eco exit to test our issues so we have to write this code in the Magento we have to write the locks and it will everything whatever you want it will written in the locks and you can check the flow like how your code works and what was the data it was passed and here you can see the first parameter is what you have to pass you can pass any variable or any array in that first field second is a null or you can specify one two or three or four it's null is a Zend lock and one two three different codes is there in the Magento one is for alert and different notifications and different type of values you can pass here and after that this is a log file name you can create your own log files or Magento already have system.locks and exception.lock you can also store there but to do this you don't have to forget to check in if you have enabled the locks in the Magento or not if you will not enable it it will not store in the locks so this is the first thing you have to check yeah so here the conclusion like points to be note for the developers what they have to note always be attentive for the performance critical code actually whenever we develop we are not looking into the performance first we are our first idea is to complete the functionality and after that we can think about the code performance or not if it it will not affect then we will not make it changes but it will work for the small systems like I have a 50 users or 100 user 200 user but whenever my system grows the actual performance of code will highlight that time so that time if I write the wrong codes which is very performance critical then at the end I will be stuck actually there is no way to make it optimize they will be very difficult for the user so from the starting we have to remember for the performance critical codes in Magento after that to avoid the useless computation inside the loops like we just so we have loading the models every time in the loop so we have to take care we will not do this it will significantly improve our Magento performance and try to learn and understand the feature of frameworks and use them correctly like in Magento is a e-commerce and which is also written in PHP so we can directly write the core PHP in Magento also so instead of doing this we have to understand what the framework is and how to write the code on that particular framework so that we can utilize the performance or the better benefits or features of that particular framework instead of writing the core codes and after that the common we have to use a common sense like sometimes we have to fetch all the data at a time like if we have a small database table sometimes we don't have to fetch all the time all data at a time we have to fetch every row in a for each which I just saw you so as per the situation we have to understand like which code we have to use either we have to fetch all at the time or we have to fetch one by one in a loop so these are the nodes which developer have to take care whenever they write any code in Magento also so this is the I cannot say it's purely Magento it's also PHP also so use developer have to maintain all these features and keep in mind whenever they develop any modules or anything in Magento so in the next this is the part one of the presentations and the best practices in Magento for the next meetup I will share many other good feedbacks or good features like how to implement the things in Magento so thank you that's for my side any questions or so it's so much answer, yeah Can you replace PHP? Yeah Can you replace PHP? Yeah Yeah So it's so much answer Yeah Can you replace PHP? Yeah So it's so much answer yeah No actually I have not tried it because as per the Magento guidelines they are suggesting to run the PHP from I think 5.3 to 7 in the co-PHP so I have not tried it actually anything else


Saya sangat gembira berada di sini. Ini sebenarnya pertama kali saya berada di sini. Jadi saya sangat gembira berada di sini. Jadi apabila saya sangat gembira, saya akan bercakap dengan dengan dengan cepat. Jadi anda tahu, saya akan berhati-hati dan saya akan melakukannya. Jadi, saya rasa anda akan melihat web-side dan saya fikir titik itu sangat lama. Jadi kami akan menghubungi Komare dan kami memutuskan bahawa kami ingin sebuah titik yang lebih kecil di sini. Jadi, today's topic is about managing complexity of DSLs and a little bit of matter. So, a little bit more about myself from Singapore. Just a short talk away so if you have some time you can pop by. But otherwise, if not, you can go and catch what's that show. Crazy rich Asians. You will see Singapore there. Except that disclaimer most of us are not rich.  So, I'm an engineer at Ascender. We're a loyalty technology company. We'll talk a little bit more about that later for some context. I work with a bunch of very talented engineers. In fact, some of them are here today. And today's topic is about the collective experiences that we've had as a team when dealing with complexity. Lastly, I enjoy reading. I do some running mostly so that I don't get fat. And I can eat more Pad Thai. And I do love movies. Wish I would think I will need your list of movies later. So, speaking of movies, has anyone seen John Wick? Cool. So, I was watching that on a plane over here. And I realized that there's John Wick 3 recently. And I'm not sure if you noticed it. When he's back for the third time, he's basically still trying not to get killed. I've watched it once, I've watched it twice, and I've watched the third one. And it's always the same thing. So, sorry, technical issue. So, yes, that brings us to today's topic. Have you had projects that are basically coming in different forms? Just like John Wick fighting the mobsters. You've got the Japanese, you've got the Russians, and so on. But he's always fighting someone and trying to survive. So, our projects are something like that as well. It's a different context, but yet the plot is almost the same. So, this is where we talk about how DSLs help to solve some of the problems that we had and how we approached it. So, to guide us a little bit more about this, we need some context. So, unfortunately, AMACS is not one of our sponsors, but here's a little bit of an example. So, I want to fly to Thailand to come and meet you guys. So, I want to redeem some points so that I can buy myself a ticket on Thai Airways. So, I go to AMACS, I redeem my AMACS points for Thai Airways points. And from there, I get my ticket. So, that is kind of the context of today's project that we'll be looking at. Our product is essentially a points exchange. And you multiply that by 20X. So, again, it's not advertising, but here's a little bit of an example. So, you could be getting points from Kung Thai here in Thailand, and then you want to exchange and maybe fly via Emirates. So, this part is brought to you by Emirates as well. So, multiply this by 20X. And it starts to introduce some scale-related issues when it comes to development and maintenance, when you're working in a sizable team of developers. So, every little integration is different in its own way. They all have got their own little habits. So, like, see when John Wick, he tries and fights all the way up to a big guy, they first come to him with their fist. It doesn't work, they use knives. It doesn't work, they start throwing axes. So, it's kind of like that with integrations as well. Everyone is a little bit special. And add on that, you know, at a project level, you've got new connections, migrations, enhancements. And, you know, as the business always says, we want this in yesterday already. So, we started to face issues on, like, you know, how we could keep up with demand at scale. So, here's a little bit of an example on how some of our content may look like. So, for example, this is a simple CSV file. We've reduced it to the essential pieces of information. So, for example, you're exchanging points and you'll be submitting your membership ID for a loyalty program. So, here's a little bit of an example over here. Of course, using this as a case, then we've got many other types of data. So, you can have it in TSV, fixed-wave files, spreadsheets, whatever, everything. And, of course, we've got APIs because everybody loves RESTful interfaces, right? So, I want to show you a little bit more of an over version over here because you've got this very weird JSON request body over here. So, here's a use case from one of our partners and it also gives us an idea of some of the issues that we face with. So, for example, if this partner they can't deal with, or rather their systems can't see, for example, the HTTP status codes, nor the haters that you typically expect in a request. So, everything goes into the body. So, here's an example of some of the varied situations that we see. So, other variants include, for example, inconsistent response formats. Sometimes you get a JSON and then a different HKs could be returning you in plain text and so on. And then, of course, you've got a bunch of feature-related enhancements as part of the project. They might say, I need you to implement like a client credentials grant to authorise you making the request and so on. And then, you've got pre-processors and post-processing. So, here's a sample of how the code looks like. I know it's quite a bit of a mouthful so I'll take you through it one by one. It really is just your typical Ruby class that helps to execute the sending of a CSV file. So, if you've got a bunch of conflicts, for example, like your file name, partner name, and so on. And then, you create a file and then upload it and so on. So, we actually had something functional here. And it's decent. It works up front when we first launched this project. However, when you multiply that by 100x, you start to see, you know, hey, this is maybe not so sustainable. In yesterday's talk with team, we talked about delegating responsibility, right? And yet, this class seems to be doing almost everything. So, we don't like that. That doesn't spark joy. So, this was our individual developers, and now it's good. This works. Nothing to complain about. Then, when the other developers look at this, like, hey, we need some Marie Kondo in the house. So, a year later, when you have to go and update the code, like, goodness, what's going on over here?  Now, everything is failing, so you've got to make it work.   So, obviously, it no longer sparks joy. So, for us, the goal was this. How do you standardise the approach of handling integrations? Can we focus on only what's custom, what's special and extract away what's common? So, for example, when you create a file, if I expand it by 100x200x creating a file, it's always the same. Maybe what's different is maybe, let's say, the delimiter. But everything else actually stays the same. It doesn't have to be appearing in that same file. So, we want to take this and apply it in all its different variations that we could possibly work with and make sure that we come up with a partner file that only has customisations, almost like a configuration file of sorts. So, like John Wick, when Betty No. 199 or integration No. 199 comes along, right? We want as a team to be able to respond as quickly and as flexibly as him. You notice, whoever comes at him, he just shoots them in the head. It's always the same thing. So, we want to do the same as well. So, for that, actually, consistency is key for us so that when you're consistent, you're quick, you're flexible, like John Wick, hopefully, and then that helps you to simplify the domain complexity of the problem. So, just very quickly, we identified three main areas that needed addressing so that we get to a very consistent state. One was the data. So, the data in this example over here is essentially two different formats, but they all achieve the same goal. It's just that the way you send it, the way you hit the guy, it's the same. So, of course, this also contains the business logic of the information that you're sending.  So, like John Wick, in order to get to the final boss, he has to go through many stages. So, this is an example of an interesting partner that uses a layered architecture with an entire organization.  So, the first one gives you the response in plain text. The second one gives you a response that's not in XML. It could be in JSON, sometimes even plain text as well. And then only then you get to your target system for which you want to fulfill your points. And that's the only one that responds in XML. So, lastly, we've got customizations. So, as the business says, you need to make everything okay. So, this was also one of responsibilities that our configuration had to handle. You needed to be able to jump in quickly to modify as needed. So, this includes special things like, oh, you need to encrypt the data. You need to be able to decrypt the data. Authorizations. You need to deal with time zones. So, this really was our goal to standardize what's common. Make every integration a configuration if you can. And each class only focuses on customization. Because this would make sure when we are refactoring our code over here, hopefully we don't have to go to the moon. We want to make it a bit simpler. So, we've actually got four steps. But for today's presentation, we just focus on two. One is preparation and the other one is delivering the data. So, here's a sample of how our DSL look like. And then we'll dive down a little to take a look at the individual parts that enable it. So, really the big idea over here was to firstly consolidate and simplify the high-level configuration. So, remember the previous file had a lot of the specific conflicts for each major type of delivery and preparation of the data. Over here, we want to put it if possible into a single line. So, we had a builder class. Then, for the rest of the file, you really just focus on what's custom. So, only if it's custom, we'll put it in here in the file, if we can. So, you notice over here, we've got the formatting configuration. But for example, we didn't put any configuration that was delivery-related. And lastly, we've got the configuration of the data, the content itself. So, this one, we will not touch too much about it because this part would be pretty straight for its business logic just like any other application that we've done. So, the first part, your high-level config. So, this is enabled for a builder class that we include directly in the partner class. And this is how the builder looks like. So, essentially, we extend a module because we wanted the dynamism to be able to specify what are the individual component classes that we want to include. So, this is where the dynamism comes into play. So, over here, by specifying the config, you say that I want a CSV or if I want to make a SOAP request. And then this is where we compose the modules in. So, here's an example of what we compose. It's an example of a CSV file. And that's really just two main things over here. So, the first section, which is kind of the meat of the logic, it's us trying to be able to define methods on a fly and assign a certain value to it. So, for example, I want to specify in a single line. Hey, my column separator is let's say a curly brace. And then this is where it happens. So, you want to be able to define a method. So, we'll talk a little bit more about how this is enabled. But essentially, here is where you specify on how you enable your CSV configs to be applied. Then the next part, preparation, that will be your execution of your business logic. So, this part is fairly standard. Once the first part is already done where you're configuring your values, then the next part is just executing the logic. So, over here, also there's two parts. So, firstly you've got your define config. So, remember just now we had configure your column separator or row separator. So, this is where it all happens. So, you want to make sure that we only customize what's needed. Otherwise, you want to be able to default it. So, for example, over here, the config method receives the config name, which is essentially when you define a method that will be your method name. Default value and a block if you want to supply some slightly more complicated logic. So, that's your first part. Your second section is where within the partner class, you want to customize the logic. So, this is where you define the method that allows you to accept the customized value. So, I'm running out of time. For more information, you can actually check out the Jam Simple Configuration that was written by our VP. This covers this logic that you see as well. So, all in all collectively, this allows us to build a pretty concise DSL that allows us to represent a partner. It's extremely efficient because considering that your domain complexity involves a lot of very small methods and values with very simple logic, this really makes it easy for the individual developer to work on changes or construct new integrations. So, actually relative to our prior classes, we managed to reduce the lines of code by 50% or more. And the classes are just very much more economical. So, in summary, here are the benefits. So, development is really fast. Testing has been simplified because we've extracted away what's common. You really just focus on testing and customizations. And it's really easy for newcomers to join us and work on a very core part of the system. Of course, on the flip side, because there's always a pricey of the pay, right? The underlying code is not so easy for us to modify, especially for new engineers. And testing can be a bit more difficult because this is essentially a building block of our entire construct. Although, at the same time, a nice side effect with scale is that when you've got complexity at scale, right? If we all write enough specs, it generally helps to cover all the possible cases that you could handle. So, even though you're modifying a particular building block, it helps a lot when you have a very good test coverage across all partners. And yes, that's it. I hope you enjoy the talk. Hopefully, we see John Wick 4. But this is us when we get a new partnership. I'm thinking I'm back. Thank you.


Like any sport football has a number of statistics that are tracked in order to compare one player to the next Because the nature of the offensive positions like quarterback and running back are so different each position has its own set of statistics So let's take a look at some of the most common you'll hear talked about on the offensive side We'll start with the running backs The simplest stat for rushers is carries Which is simply the number of plays in which they receive the handoff or carry the ball Another common stat would be the number of rushing yards a player has a key element to remember from this stat Which will also hold true for a few others We'll see in a moment is that the number of yards starts at the line of scrimmage So even if the running back receives the handoff five yards behind the line of scrimmage and runs forward ten yards It will technically have been a five-yard run that is the five yards from the line of scrimmage forward Something else to note here is that if a running back is to receive a handoff and then is tackled behind the line of scrimmage He will be credited with negative rushing yards a third stat for running backs is the yards per carry Which is simply the number of rushing yards divided by the number of carries Two half backs may have the same amount of rushing yards But the player who did it in half of the rushing attempts are half the number of carries is obviously more impressive Let's move on to receivers who will be catching the ball rather than having it handed to them Even still their stats are actually pretty similar to running back stats The receivers equivalent to the number of carries is the reception which is a simple count of the number of times they have caught a pass Receiving yards are the ground gained from those passes Although like rushing yards the count is made from the line of scrimmage to the spot where the receiver is tackled Even if the quarterback drops back 10 yards behind the line of scrimmage that distance in the backfield is not counted You may also see a stat called yards after catch Which is some indication of how good a receiver is at evading defensive players For example, our first receiver can run forward 10 yards turn around catch the ball and then get tackled on the spot Our second receiver might run forward five yards make the catch run forward five more yards and then be tackled Both of these plays resulted in 10 receiving yards But the first receiver had zero yards after the catch while the second guy had five yards after the catch Again, this tells us a little bit about how good the receiver is at avoiding being tackled But as we saw here the root in the defense of positioning also factor in You might also hear someone reference yards per reception, which is kind of like yards per carry It's simply the number of receiving yards divided by the number of receptions The third offensive position we'll look at is the quarterback who probably has the most stats connected to him To start simple we have pass attempts, which is self descriptive just the number of times the passer has thrown the ball Next we have passes completed, which are the number of pass attempts that have been caught by a receiver Passing yards are similar to receiving and rushing yards again The yards are not counted until the line of scrimmage, but all yards after the catch are included in passing yards as well You will likely see a ratio of touchdown passes to interceptions thrown pop up at some point Touchdown passes, of course being the number of passes that resulted in a touchdown and interceptions being pass attempts that were caught by the defense Yards per completion can be difficult to compare from one quarterback to the next Because some teams will emphasize many short passes rather than rushing plays and fewer but longer passes But you kind of get the idea Finally a negative aspect of being the quarterback is that you will be holding the ball so much And therefore you will be chased by a lot of guys who are trying to tackle you If these defenders are successful and tackle the quarterback behind the line of scrimmage It will count as a sack both for the quarterback and the defensive team If a quarterback is able to slip away from the defenders, however He can run the ball himself and pick up some rushing yards of his own


A few of you requested that I do a before and after vid on Catherine Payes of the Ace Family, so here it is. It only made sense to do hers considering I just did her BFF, Chantelle Jeffries, before and after Transformation 2. Catherine's real name is Dolores Catherine Payes, and although her family is from Panama, she was born in Montreal, Quebec. At the time of this recording, she is 29 years old, and her Instagram following is at 7.3 million followers. Even though Catherine was born in Canada, she moved to Tampa, Florida and grew up there. Catherine then went on to attend St. Louis University, the same school as her man Austin McBroom. Catherine was a model and actress from a young age, so it only made sense to move to LA afterwards to pursue more opportunities. I guess she found what she was looking for there considering her and her family currently still reside in LA to this day. If you're familiar with Catherine then you know she rose to fame with her now husband Austin, who she has two daughters with. They're best known as the Ace Family, who found huge success with their YouTube channel which now has over 17 million subscribers. I'd say they're the most famous YouTube family, that's for sure. These days Catherine is not only still a YouTuber, but is also a famous influencer across other social media platforms and an aspiring TV host. Being famous on YouTube and always being involved in Hollywood, it's no doubt that Catherine has made some changes to her appearance. This pretty much comes along with the territory. So in this video we're going to be taking a look at Catherine's transformation over time. She's admitted to getting some work done like a boob job, but not everything else. And fans do speculate that for sure there has been more. What's going on guys and girls, my name is Cara and this series we've titled Before and After. Today we're going to focus on Catherine, any cosmetic work she's had done or what's speculated, her body, fitness, and just how she's evolved over the last little while. I've done other celebrity transformation videos including ones on her BFF Chantelle Jeffries and Lele Ponds and we'll have links to those at the end of this video. You've also been reading all your comments and I'm going to be responding to some at the end of this. As always if there's anyone else you want me to document let me know in the comments down below. Now let's get into this video. Let's start with Catherine's face. Catherine denies getting any work done to her face but when you compare pics from then and now you can see some noticeable changes. Catherine's nose is actually perfect but it hasn't always looked like this. I think getting a nose job can change your look quite a bit so that's one of the reasons I noticed it so much. Catherine's nose before was a bit larger and had a slight bump but it still suited her face. These days her nose is super sleek and petite with zero signs of any bumps or imperfections. The difference is the most obvious I think when you look at her side profile. Clearly a lot of fans think the same thing. Considering Catherine has never admitted to a nose job this is all just speculation but I'm pretty positive she's gotten one. What do you guys think? Looking at the rest of Catherine's face I would assume she hasn't got any other major work done probably just some non-invasive stuff. Reading some threads online fans also said what they think she had done. For example one person said, I suggest you go to the Catherine page before Instagram page and there's proof specifically of the nose job.  It doesn't take a genius to know that. Interesting. I definitely think she does the lip fillers considering her lips were nearly as full back in the day. Although they weren't that thin and looked nice all natural and most of her photos these days they have that extra plump look to them. I know that everyone edits their photos and can hide flaws with great makeup but I think it's possible that Catherine also uses fillers and or Botox in her face too. Seeing as she's almost 30 she may use it to keep herself wrinkle free or even to accentuate certain parts of her face. I think she does look pretty different though. Finally I think that Catherine has veneers on her teeth but only because they are way too perfect, white and straight. The girl does have a great smile though so whatever she did it worked. So I'm not 100% sure about the changes Catherine has made to her face over the years but it seems like she was always naturally pretty. Being a social media star and living in Hollywood I'm sure has the most pressure so if she does get some cosmetic work done I'm really not surprised. I want to know what you guys think though. Has she gotten all those fixes that people think she did? Let's move on and look at Catherine's body. First off the only work that Catherine admitted to having done on her body is a boob job. It seems like Catherine always had a nice body which shouldn't come as a surprise because duh the girl is a model. Still she did look different back then. Fast forward to now and two kids later Catherine still has a picture perfect body and maybe even nicer than before. So the question is is it all natural? Well like I said the boobs aren't but we know that. Catherine said she didn't really need a boob job but got one a few years back and that definitely made them a lot bigger when you compare pics. I actually can't find too many pics of Catherine pre-boob job. Anyways Catherine was really open about this procedure because she apparently would get asked a lot about it. Some years ago on Instagram she posted a photo talking about her boob job saying ladies so I find myself getting tons of emails regarding my breast augmentation and figured I might as well post this. I did the procedure about three years ago and went with saline under the muscle incision through the armpit. I have little to no scars due to it being done on the crease of my armpit. Very open about it and although I didn't need to do the procedure I have no regrets. Life's too short to not go through the things that will make you happy. Well said Catherine but I think she had to be open about her implants considering they were pretty obvious especially when they were new. That post was pretty old though and Catherine said that she got it done 10 years ago as of this year. As we know she's had two kids now so I'm not sure if that was the only boob job or if she got them fixed up post babies. We know Cardi B got some post baby work done to her boobs and some lipo. We even did a video on Cardi's updated before and after too if you wanna check that out. Fans have also speculated that Catherine got lipo maybe after becoming a mom but it's unsure. It seems the girl does work out extra hard and commits to staying in shape so it could just be good old fashioned diet and exercise. Finally I wonder if Catherine got a Brazilian butt lift or any work done back there. Some comments that people have posted in threads online say that for sure she has but I don't know if I believe it. There was a video her and Austin posted on IG a few months back of Catherine dancing on Austin in the mirror and it got people talking. People said that her butt must be fake since it looks so much bigger now and after seeing that clip and the photo I can see why. In some past photos like after Catherine had their first baby from the side view her booty looks a lot flatter. Catherine has said that since her pregnancies her weight has fluctuated quite a bit and there have been times before when she's lost a lot of weight because of breastfeeding and stress for example. This all does make sense because we all know that weight changes can make the butt shrink or grow bigger. Her and Austin even addressed the fake booty rumors in a vlog. So yeah like I said I gained 60 pounds during my pregnancy a lot of Latina girls or a lot of people in general can relate to this where you gain your weight first in your butt so I gained weight in my butt and in my thighs first and then my arms and my arms actually the one place of my body that's really hard to lose weight. And then went on to explain that they were natural changes after having her second baby and definitely not about lift. Guys the truth is. I have not done anything to myself. The truth is this booty is natural. Stand up. No I'm not doing that right now. I'm not doing that. Shit they need to know that booty is natural.   I don't even have massages. And you will never do anything to that butt. Yeah I won't. Anyways they seemed pretty convincing to me. I think I'll let the booty rumors slide. Whatever Catherine is doing she looks amazing for someone who just recently had two kids but we'll be looking at how she keeps herself fit next. So if you follow Catherine you'll know that she bounces back quickly after having babies. I'm sure it's not exactly easy and it definitely takes some discipline. After her second child was born she recently post on Twitter a photo showing off her bod with Austin. Writing, five months postpartum.  Trained in silence without having to prove anything to anyone but yourself. Feeling myself again. So what did Catherine do to get herself back in shape? According to her she just exercised a lot. Not only did she work out post baby she also exercised while she was pregnant which helps a lot to keep you in check. Her and Austin posted some vlogs of her pregnancy workouts and I'm sure it helped having her man to train with her and keep her motivated. Let me show y'all. So we're gonna stand straight up, arms out, get the balance, but always tight. Down, good, up. Down, good, up. Get low, get low, honey. Get low, good. There we go, there we go. I think it's definitely easier to exercise if you have a workout buddy, especially if they are just as motivated as you. It also doesn't hurt if it's your boyfriend or significant other. Not only does she do at home workouts, but Catherine spends a lot of time in the gym too doing a variety of cardio, weights and other activities. She also goes for runs or hikes which doesn't surprise me because when you live in LA you have to take advantage of those hills and views. I'm not sure if Catherine has any specific diet but I would assume she eats pretty healthy. It seems like everyone in Hollywood does. From watching her vlog, she doesn't mind cheating either though. I know the girl likes crispy cream donuts, but they're my weakness too. For the most part, it seems like Catherine's hair and makeup look has stayed pretty similar over the years. Although she's had dark hair before which you can see in really old photos, she's been the same color for a while now which is like a dirty blonde highlighted brunette look. Damn, I love you. Wait, can you tell? Yes. What is it, what's the difference, tell me. The color, it's a little lighter. Uh-huh, and? And it was cut a little bit. A little trim, yes it was. There was no trim. Not one trim. And you had a little twirl to it. Is it the roots? And then I colored the hair and highlighted it. Yeah. I think when you compare pictures, her current hair definitely suits her the best so I'm sure she'll stick to it. Catherine is a natural beauty who seems to look great without having to do much. I think that people online can be extra critical towards her just because her and her family are so famous. Although some speculate that Catherine got a lot of work done to look the way she does, I do think some of it is just rumors. I think that Catherine's post-baby body is the way it is because she exercised during and after her pregnancies. But who knows? I don't think she has a fake butt or life on my opinion but I think that she got a nose job. Those are just my thoughts. Let me know if you guys think I'm right or wrong in the comments. Whatever she has or hasn't done, Catherine will just keep enjoying her ace family YouTube success and either way, her and Austin have made a super cute family, clearly considering how much everyone loves to watch them. Okay guys, so just like before, it's time for me to read out some of your comments from our previous videos. This one is from our Lindsay Lohan before an after vid, Alar Lillavalli said, in my opinion, she looks really good now. Yay, finally a positive comment for Lindsay. I think she needed that. Honestly, I was watching Mean Girls the other day and I remembered just how much I love her. On her Ariana Grande house tour video, Omzi said, love this channel. Thank you so much, Omzi. I like knowing that you guys are enjoying the videos. And finally, from our Tana Mojo before and after, Rachel Smythe said, it's probably a non-surgical nose job so they use fillers to make everything look even. I mean, we all know she's been so open about getting filler. Good point, Rachel, that very well could have been the case. I just assumed that it was a nose job because she needed that non-cosmetic one in the past. But fillers could definitely give her nose that straight and perfect look too. All right, guys and girls, that wraps up this video here and before and after. If you wanna talk more about Catherine's transformation, you can hit me up on Instagram. Let me know who else you would like me to make a before and after video on and I'll see you guys in the next video. And if you haven't yet, hit that subscribe button. I wanna get to know you guys better and hear more of what you have to say. Let's get the 50K to 100K. Bye.


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Welcome dear learners, today we shall discuss about wheat management in tea. We shall discuss about wheat in tea plantation, their types and their management practices. Before going to the main contents, let me define what is wheat? Wheat are basically the plants growing in an area where they are neither desired nor appreciated. Wheat compete with the crop for the nutrients, sunlight, carbon dioxide, moisture and space. Most of the wheat's harbore may many paste and diseases which attack the main crops. Some wheat hinder harvesting of tea by covering the plucking surface and also creating physical obstruction to the pluckers. So in tea plantation, wheat is not a major problem, especially in case of mature tea, because mature tea canopy covers the ground. But nursery and young tea plants suffers a permanent setback in vigor if proper wheat control measures are not taken at appropriate time, which are a problem in prune fields and need to be controlled till the puses cover the ground. Now when the wheat competition is more in tea or any other crop field, there are some critical period of wheat competition in tea garden and if you see in the case of Assam, a state of northeastern India, the critical period of wheat competition is between April and September that is during the monsoon. Now what are the types of wheat? How these wheat are classified? Wheat are classified on the basis of duration of their life cycle as annuals, biennials and perennials. Morphologically, maize or wheat belong to either monocotillatinas which are having narrow leaves or dicotillatinas which are having the broad leaves. Now in tea garden, what types of wheat are normally seen? They are spaces of grasses, monocotillatinas and dicotillatinas which basically infest the tea fields. Some example of wheat seen in the tea garden of major tea growing area of the world are like annual meadow grass, bermuda grass, torpedo grass, polygonum, American drop, large leaf, wood, choral. So these are common weeds which are dominant in the tea growing area of the world. Now come to the control method that is how we will manage these weeds. There are various control methods. Among those if we see the mechanical methods hand weeding, sickling, chilling, forking and malsinger generally done for wheat control in tip plantations. Hand weeding is carried out in the nurseries and in the newly planted tea areas where application of chemical herbicide is prohibited or hazardous for the young plants. Chilling that is also called as surface scraping. It is an efficient means of suppressing wheat with a minimum soil disturbance. Chilling is useful in controlling the cellar rooted wheat when their density is high and a large area is to be weeded. Now sickling. Sickling is basically done to control the vigorous growth of tall weeds and deep rooted weeds growing around the collar of the bushes can be removed by forking. Another important operation is mousing which is very effective in controlling wheat growth. The growth of wheat has to be constantly checked before they reach the flowering phase. Therefore the weeding should be done at least every 8 to 10 weeks so as to control them before they reach a height of 10 to 15 centimeter which is also facilitated fertilizer application. The border areas of tea fields, roadsides, steeps there and etcetera should be kept wheat free by slush weeding in order to avoid continuous dispersal of wheat seeds to the adjoining tea fields. Now let's see the effect of weeds at different stages of tea plant. In tea plantation, weeds are seen from the nursery to the mature tea field. However in mature tea field the wheat infestation is less as I have mentioned earlier. Early and young tea plants are more susceptible to wheat infestation therefore proper wheat control methods need to be followed. Generally we should avoid the only chemical method of wheat control as much as possible. In what happened in nursery plant up to 6 months of planting of cuttings application of chemical is strictly prohibited, totally prohibited and rather it is better to follow integrated wheat management practices where manual chemical, biological and ecological methods are combined in order to achieve cost effective and eco friendly wheat management. So dear learners we came to the end of the discussion and it is seen that if proper management is not taken at proper time which can create serious problem in the tea plantation.