When Paula Gordaliza began working on the application of statistical theories to create fairer algorithms, in 2017, artificial intelligence (AI) was still being talked about in the future tense.. Today, scientific articles on the topic accumulate every week and debates about the increasingly central role that algorithms occupy in society are omnipresent.

His line of research is at the heart of one of the most important conversations: his work aims to design and analyze machine learning methods that detect, control and correct possible biases in the results, which will contribute to creating fairer algorithms, eliminate discrimination in the results and, ultimately, “make the population trust more in artificial intelligence”, in his own words.

Trained at the universities of Valladolid (UVa) and Toulouse III-Paul Sabatier, she is a postdoctoral researcher at the Basque Center for Applied Mathematics (BCAM), in Bilbao, and an associate professor at the Public University of Navarra, positions from which she claims the role fundamental of mathematics. “Many professionals are involved in artificial intelligence, but the basis provided by mathematics is what allows us to solve problems,” he says.. This year, his work has earned him recognition from the Vicent Caselles Mathematical Research Awards granted by the Royal Spanish Mathematical Society and the BBVA Foundation.

We tend to think of machine results as something neutral, objective.. What does it mean to talk about biases in artificial intelligence? In reality, artificial intelligence does what it is told to do, nothing more. But to work it needs data and some of the main biases that appear in the results actually come from the databases with which it works, which are often the ones that are biased, for different reasons.. In recent decades, an effort has been made to take care of the data collection process, but many times we find certain groups that are more represented than others and that conditions results. So the biases are in society, in the human part of the process. We are seeing it in some of the ChatGPT results, which privilege English over other languages or which can perpetuate certain stereotypes in genders or social groups. In part yes, because the algorithm that powers the AI learns from the data we give it and Any bias that that information contains will also be learned (and in some cases, even worse).. Those examples that you mention are one of the ways in which it manifests itself, because it is common in the new artificial intelligences, called generative, where it is seen that it is necessary to do work to detect and reduce these biases. And what role does statistics, and in particular the theory of optimal transport, in that effort? Like many other answers in mathematics, the theory of optimal transport arose to answer a real and concrete problem. In this case it appeared with the so-called Monge problem, to know how to transport a volume of mass in the most effective way possible (from a pile of sand to a hole).. As a result of this approach, an entire theory is developed and applied to the field of statistics, where it is very important in relation to the concept of probability measurement: In short, it is about transferring one probability measure to another with the least possible effort. How is it related to AI? Regarding AI, in the simplest case we can have a database with a sensitive variable, such as gender. And we want to erase the influence of that variable, so that when the data is used the algorithm cannot reproduce biases.. So what we try is to match the rest of the characteristics. Specifically, our idea is to transform the two original distributions of men and women, making them as similar as possible in the rest of the variables and thus erase the possible influence of that protected attribute. The fact that many of the AI tools that are based on the machine learning publish results without being able to know the process (the so-called black box problem) is one of the sources of distrust towards this technology. That is the great objective of mathematics, trying to apply rigor through theory, obtaining results powerful that open those black boxes and that society can trust more in the process. Sometimes these solutions that algorithms give us can be attractive, because it is seen that they work, but they lack sufficient traceability to know how they are reached. It is a field where public-private collaboration is fundamental, what is investigated has a clear and immediate practical application for society. How do you see this company-university duality? Research is always ahead of applications, especially in mathematics. But it is true that there is an increasing demand from companies for methodology, strong methods to solve problems in society, which are increasingly complex and multidisciplinary and which also require multidisciplinary teams (not only mathematicians and statistics).. I think it is positive that the industry offers us more and more real problems, which serve to motivate research, because this type of synergies is something that is of increasing interest. And what is missing for these synergies to increase? I think they come together different issues: on the one hand, companies are very protective of their own data or those of their clients, which can generate problems with confidentiality. There is also the fact that companies have their own methods and processes, for which in some cases they pay a lot of money and which are difficult for them to separate themselves from. Mathematics in particular is a discipline that is difficult to make visible, despite its importance. Mathematics has had a bad reputation since school, since we were little, because it is considered difficult. But the truth is that they serve to solve problems and today we find increasingly complicated problems.. We must try to get the message across that mathematics is not only necessary, but is useful for everything.. They are a constant that is behind any advance and any science.. That is why I believe that many times young people who are considering what profession to choose, what to train in, feel attracted to other disciplines that are more applied than basic mathematics.. In my point of view, specialization is forced too soon.. Skills and basic knowledge should be deepened. So that young boys and girls who are attracted to artificial intelligence, for example, have a foundation in mathematics, statistics and other areas. And when they are ready, with a toolkit of those basic concepts, they can make the leap to more specific concepts.

Jennifer R. Brown is one of the specialists who best knows chronic lymphocytic leukemia (CLL), the most common form of leukemia among the adult population in the Western world.. This is attested to by his more than 150 published articles and his contribution to the clinical development of treatments for this blood cancer.. The director of the Chronic Lymphocytic Leukemia Center at the Dana-Farber Cancer Institute chairs this weekend, until Monday, in Boston, the congress of the International Workshop on Chronic Lymphocytic Leukemia (iwCLL), a world leader in the study of CLL.

Brown advocates a scientific mentality in medicine. After completing a bachelor's and master's degree simultaneously in Molecular Biophysics and Biochemistry at Yale, he entered Harvard Medical School, where he earned a doctorate in Molecular Genetics; Later, he completed his residency in Internal Medicine at Massachusetts General Hospital and specialized in Hematology and Medical Oncology at Dana-Farber in Boston, where he has focused on the treatment of chronic lymphocytic leukemia (CLL).. The arrival of new medications is making the prognosis for this oncohematological disease among the most promising.

In your training as a doctor, biology sciences have had a specific weight. How has that influenced your way of working with patients? Having both types of training is important for developing new medications; The biology part allows you to think about the characteristics of the cancer cell that we want to target, it makes you wonder what should we look for to design a new treatment? I think it is very useful to resort to a scientific mentality in clinical practice. For example, when we did the first human trials with ibrutinib and idelalisib we saw that patients felt better with the treatment and that the lymph nodes shrank, however, the white blood cell count increased.
At first glance, this data indicates progression, that they are getting worse, but I looked at the patient, I saw that he was feeling better and that the lymph nodes were also improving, so we continued with the medication. Thus we realized that the cells left the lymph node and bone marrow and entered the blood, where they did not have a medium to sustain them and they died.. That is why the leukocyte count increases during the first weeks, then stabilizes and eventually returns to normal in many cases, but not always.. But it didn't matter, as long as the patient continued taking the medication, he remained in sustained remission.. That way of thinking also applies to identifying future goals for finding new drugs for this disease.. Perhaps that contribution is still undervalued both in our academic culture and in funding, and it may partly explain why it has taken us so long to get to the point we are at now.. Finally, we have many new medications, targeted drugs and immunotherapies, and we have been slow, in part, because this chasm has existed. Chronic lymphocytic leukemia (CLL), a disease in which he is a specialist, is said to be a “good” cancer. “, due to its slow growth. What is the prognosis today for this disease? Well, I don't like to tell a person who has just been diagnosed with cancer that they have “the good one,” but, yes, it is true that after a few months or years, some of the patients come back and say: well this is really “the good one”. After overcoming the shock of the first diagnosis and getting used to living with it, there is some of that. There are two types of CLL: low-risk, which may never need treatment or go into very long remissions, and has mutations in the IGHV region; then there is the one with the highest risk, without the mutations. These data suggest that patients with IGHV mutations have a basically normal life expectancy compared to that of the general population.. People with the disease in the absence of mutations still run the risk of dying prematurely, but I always tell them that my goal is for them to reach their natural life expectancy and I think we are achieving it in many cases. Many things are really being achieved with new treatments, and there are also trials with advanced therapies.

I don't like to tell a person who has just been diagnosed with cancer that they have “the good one.”

In patients at higher risk, what are the main causes of mortality? Above all, we are concerned about infections in these patients, and also about the appearance of new cancers, unrelated tumors such as breast or prostate, or skin cancer, in particular. , melanoma. You have mentioned the new medications that are being used in CLL; Among these options are Bruton's tyrosine kinase (BTK) inhibitors, a family made up of several drugs, among which the doctor must choose. What is his recommendation? It is true that there may be some confusion, because there are different drugs. who are heading to BTK. Ibrutinib is one of them, it is a first generation drug, it was the first covalent inhibitor and it is associated with many side effects, which we have not seen with other inhibitors, such as severe skin rash and diarrhea.. Then came second-generation inhibitors, such as acalabrutinib and zanubrutinib.. Both are much more specific for BTK than ibrutinib and, in comparative trials, improved the safety of ibrutinib. So now those are my two BTK inhibitors. I have been using mostly zanubrutinib due to comparative data showing better efficacy, but acalabrutinib is possibly quite similar. And then there's pirtobrutinib, a non-covalent BTK inhibitor, which I don't like to call third generation, because it's actually a different class of drug, it has a different mechanism: they are non-covalent or reversible.. The value of this drug is that it was developed to work in patients whose disease has progressed with previous generations of covalents and who have mutations that affect them.. We have learned that there are mutations that are associated with drug resistance; we try to find out the exact frequency of these mutations. In the future, there are also BTK degraders, of which we are beginning to have preliminary data. In my opinion, they are still awaiting a clinical proof of principle, but they should work after any of the other drugs, in any mutation, because they degrade the entire protein. In Spain, zanubrutinib was approved very quickly, in nine months, for three indications (CLL, marginal cell lymphoma and Waldenström macroglobulinemia) when it takes an average of 21 months from EMA approval to incorporation of the drug into the SNS. In the United States they don't have that problem, but what does that quick approval tell you? Yes, our problems are different. It is true that once the drug has been approved by the FDA, anyone can prescribe it, but then the patient may have one of the insurance companies that cannot or will not cover it, or do so at different levels.. So you have to deal with these insurance companies on each patient. Leaving this aside, it is true that the results of the Alpine study [with zanubrutinib] that we presented last year at ASH [annual meeting of the American Society of Hematology] and that were simultaneously published in The New England Journal of Medicine were surprising to many. part of the scientific community for the benefit they showed. And probably these good data have driven a rapid incorporation of the drug. Does it make sense to investigate combinations between the different BTK inhibitors? It is interesting: there has been a lot of discussion about whether we can combine them with each other and I am not very sure, because the union of both could be antagonistic. But there are other combinations that arouse interest, such as those of BTK inhibitors with venetoclax, especially in first-line therapy: also in recurrent disease.. Most of the data we have is with ibrutinib and venetoclax, so we are looking forward to more information with the second generation covalent inhibitors; We hope that the toxicity will be less. These types of targeted therapies have reduced the need to use chemotherapy in certain patients. Taking into account that CLL is usually diagnosed in older people, does this mean an improvement in their quality of life? Definitely, especially for the elderly patient. In the US, the average age of diagnosis is around 70-71, and then, generally, several years pass until treatment, so they begin to receive it in the middle of that decade. BTK inhibitors and their combinations are generally better tolerated than chemotherapy, at least this is the case with second-generation BTK inhibitors.. So I think patients are happy with that.. However, chemotherapy has curative potential in a certain younger group of patients, who tolerate it better. With these new treatments, can we talk about cure in CLL? We do not use that term in a chronic disease, although it could be said that It is achieved with allogeneic transplant and in a low-risk subgroup with FCR [fludarabine, cyclophosphamide and rituximab], which was our best old chemotherapy. Maybe later we will see that a pharmacological combination can equal what FCR chemotherapy did, but we are talking about 15-year follow-ups, we don't know yet. To me, those are the only populations where we have evidence of healing. I'm concerned that maybe we're not going to see it with venetoclax-based regimens, because if you look at the CLL14 study, with venetoclax and obinutuzumab, when they stop taking the drug, there is relapse. My view on how we can move forward is to do some type of consolidation treatment, perhaps with bispecific antibodies or even CAR-T cells, in those with high-risk disease.. An immunotherapy could make a difference, but those trials are just beginning.

Perhaps it has taken us so long to reach current medications because of the traditional gap between basic and clinical research.

What advances related to this leukemia would you like to see soon? I think pirtobrutinib, the non-covalent BTK inhibitor, will be approved for CLL and that is another line of therapy for people whose disease is progressing. It will also be interesting to see what happens with the combinations of venetoclax and BTK inhibitors. Third, there are the new targets. We have BTK, BCL-2, PI3K inhibitors, anti-CD20 antibodies, but we need other targets. In that sense, I am interested in ROR1, because it seems to be activated in all the cells of patients whose disease has progressed with the other inhibitors. So we're trying to do a trial with that.. It is a potentially interesting objective, and we want to get started with it.
I would also like to see more advances in genomics, which has always been a big field of interest for me.. We should not treat all patients in the same way, we must subdivide them better. We are finally beginning to accept that diseases with IGHV mutations and those without them are different. Hopefully we will understand what happens to subgroups based on other mutations, such as Notch, and whether there may be specific treatments associated with them. I hope that based on the great genetic sequencing efforts that we are carrying out internationally we can continue to advance.

In 1997, an American company invented the first invisible orthodontic system. He revolutionized the dental sector with a technique that is now preferred by doctors and patients to treat dental malocclusions.. 20 years later, Geniova, a 100% Spanish company, once again revolutionizes the world of orthodontics with an innovative hybrid system. We interviewed the company's CEO to learn first-hand about the potential and advantages of this new patent.

Carlos Arroyo, general director of World Patents in 150 countries.. How is this achieved? With a lot of human talent, enthusiasm and investment. Imagine what it means to invent something, test, make mistakes, correct and try again.. And that, doing it hundreds of times. And, from there, create a patent model and go country by country registering it. The one in the US has been one of the ones that has cost us the most. 18 months in total. And we have just started the FDA approval process to be able to start marketing.
Now is when we have begun to expand internationally, at first slowly but surely, to pick up speed and accelerate. How have these years of development been? I imagine they are tough, right? Years of pride and resilience. We have faithfully completed the stages of a startup. From the conceptual stage to the growth and scalability stage, which is what we are immersed in. Growing in double digits thanks to the high demand from prescribing doctors. What are the advantages of this new technique? Meeting the objectives in the established time. This has always been the biggest problem that invisible orthodontics has had since its birth: that the prescribing doctor can plan a dental movement and achieve it in the stipulated time with the defined splints.. Now, Geniova, thanks to its patent, is able to help you fulfill that digital planning with a higher percentage of success.. The treatment lasts less and is not extended over time with the use of more devices than those initially designed. What does this innovative system consist of? It is a fusion of existing and proven technologies: the bracket and the transparent splints. With all the good things about each one and minimizing their shortcomings.
What we have achieved is to digitize the bracket and stamp it on the splint itself, so we can direct the movement, and the lingual NITI arch is what generates the movement force. Exactly the same as the biomechanics of traditional fixed orthodontics, but being invisible. This arc allows for much greater efficiency in generating that movement.
Our patented accelerator is used in the initial phases for arch shaping and alignment, i.e. space generation and transverse movements.. Precisely the movements that are most difficult for splints. Once this initial phase is over, the treatment continues until completion with our own transparent splints. What future plans does the company have? Many. We have just started. We are already solving complex cases in combination with complementary auxiliary appliances; and we are finishing developing orthopedic functionalities integrated into our devices; treatment in children with mixed dentition… And, in the future, incorporate the rectangular arch to have total control of three-dimensional movements. That is costing us more due to the materials that exist right now for direct 3D printing and their limitation in production for large volumes. For something so important, I imagine that you will have a leading team… It is always the most important thing, the human team. Us. Always. But in a startup, even more so. Imagine: when we started there were 5 of us; now we are many more. But our goal remains the same: to attract the best possible talent and take care of them.
I want to take this opportunity to publicly thank each of them. To those who are and those who are no longer. Without them, none of this would have been possible.