Introducción

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 Book Index
Source Chapter

Introduction


Bruxism

  • Status quo and Criticity
  • 2rd Clinical Case: Pineal Cavernoma
  • Conclusions

Occlusion and Posture

  • Status quo and Criticity
  • 3th Clinical Case: Meningioma
  • Conclusions

Orofacial Pain

  • Status quo and Criticity
  • 4th Clinical Case: Eaton Lambert myasthenia
  • 5th Clinical Case: Postpoly syndrome
  • 6th Clinical Case: Temporomandibular disorders
  • Conclusions

Are we really sure to know everything?

  • Status quo and Criticity
  • 7th Clinical Case: glioblastoma of the cranial base
  • Conclusions

Connectivity and Complex Systems

  • Definition of the Fundamental Unit
  • Structural and functional connectivity Separation
  • Understanding of "Emergent Behavior"
  • Connectivity measurement

System Inference vs Symptom Inference

  • System Stochasticity
  • Markov chains
  • Inference of nonlinear Markov processes
  • Understanding of Network nodes

Neurophysiology and network nodes

  • Center of the Masticatory Pattern
  • Mesencephalic mechanisms
  • Trigeminal Motor nucleus

Sensory network nodes

  • Proprioceptive mechanisms
    • Neuromuscular spindles
    • Sensory mechanisms from the depressor muscles
    • Golgi Tendon Organs
  • Role of impulses from the neck muscles
  • Periodontal and Oral Sensory Factors
  • Pharyngeal sensory factors
  • Reflex of mandibular closure
  • Sensory factors of the TMJ

Conclusions to the Source Chapter

  • information transferred over time
  • System Coherence Recovery
  • 8th Clinical Case: Coherence Recovery in ort Orthognathic


Crisis of the Paradigm

Research Diagnostic Criteria (RDC)

  • Sensitivity, Specificity and Predictive Values
  • Advantages and limitations of the RDC


Masticatory cycles

  • Jaw opening width
  • Speed of mandibular movement
  • Complexity of chewing kinematics


Temporomandibular Joint

  • Computerized Tomography of the TMJ
  • Magnetic resonance imaging of the TMJM


Mandibular kinematic replicator

  • Advantages and limits of pantography
    • Pantographic Reproducibility Index
  • Advantages and limits of axiography
  • Advantages and limits of the electrognatography


Transcutaneous Electric Nerve Stimulation

  • Free way space before stimulation
  • Free way space after stimulation
  • Closing trajectory from TENS


Electromyography(EMG)

  • Interferential EMG
  • EMG at rest position
  • Quantitative analysis of the EMG
    • Fourier transform
    • Wavelett


Extraordinary Science

Overall view of the Masticatory System

  • Trigeminal electrophysiology
    • Electric Motors Evoked Potentials
    • Magnetic Motors Evoked Potentials
    • Jaw jerk reflex
    • M-wave
    • Masseteric Mechanical Silent Period
    • Masseteric Electric Silent Period
    • Masseteric Laser Silent Period
    • Recovery Cycle of Masseteric Inhibitory reflex


Trigeminal System Connectivity

  • Definition of the Fundamental Unit
    • Maximal Neuronal Energy Evoked
    • Organic motor symmetry
    • Functional motor symmetry
    • Renormalization
  • Separation of structural and functional connectivity
    • Organic vs Functional Symmetry
      • Functional Neuro Gnathological Index "NGF"
  • New paradigm in masticatory rehabilitations
    • Prosthetics
    • Implantoprosthetics
    • Orthodontics
    • Orthognatics

 
 


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Nos gustaría que nuestro lector tuviera una percepción inmediata de los temas que serán debatidos en Masticationpedia; repasaremos algunos de los temas más actuales sobre la evolución epistemológica de la ciencia en general, y de la medicina médica y odontológica en particular.

You can also watch a video of ours on Youtube, for your convenience.

En esta fase consideraremos dos aspectos fundamentales del Progreso de la ciencia, según los Paradigmas de Kuhn, y la Epistemología que cuestiona los conceptos de "Inferencia estadística" y "Interdisciplinariedad".

Estos dos temas, que aparentemente parecen estar en conflicto entre sí, ya que el primero necesita disciplinariedad para resaltar las 'Anomalías en el Paradigma' y el segundo necesita Interdisciplinariedad, se integrarán a través de un elemento resolutivo que consiste en "andamios metacognitivos", es decir, puentes cognitivos entre disciplinas especializadas. En este contexto, por lo tanto, el lector podrá apreciar mejor el enfoque estocástico hacia uno de los temas más controvertidos en las rehabilitaciones masticatorias, como es, "Maloclusión", del cual provienen la mayor parte de los procedimientos de rehabilitación masticatoria como ortodoncia, prótesis y cirugía ortognática.

Entonces, además de anticiparnos al aspecto científico y filosófico de Masticationpedia, finalmente nos enfocaremos en temas como "Sistemas complejos", el "Comportamiento emergente" de los sistemas complejos y la "Coherencia del sistema": pasos necesarios para introducir temas clínicos científicos que traen con ellos dudas, interrogantes y al mismo tiempo innovaciones paradigmáticas tendientes a cambiar el status quo de la “rutina” del pensamiento clínico determinista y reduccionista, ante una lógica de lenguaje estocástica e interdisciplinar.

Masticationpedia
Article by  Gianni Frisardi

Ab ovo[1]

Antes de llegar al corazón del tratamiento de Masticationpedia, conviene una premisa, que concierne principalmente a dos aspectos de la realidad social, científica y clínica de la era actual y la inmediatamente anterior.

En el último siglo, fuimos testigos de un crecimiento exponencial de las "innovaciones" tecnológicas y metodológicas específicamente en la odontología.[2]; estas innovaciones han influido de alguna manera en las estrategias de toma de decisiones, opiniones, escuelas de pensamiento y axiomas con el fin de mejorar la calidad de vida, como se indica en la "Ciencia de la exposición en el siglo XXI".[3]. Sin embargo, este crecimiento exponencial trae consigo, implícitamente, áreas grises conceptuales (en términos prácticos "efectos secundarios") que en ocasiones se subestiman, pero que pueden poner en tela de juicio algunas certezas científicas o hacerlas menos absolutas y más probabilísticas.[4]

Las fases del cambio de paradigma según Thomas Kuhn

Los dos aspectos sensibles de la realidad social, científica y clínica actual (que parecen entrar en conflicto entre sí, pero que como veremos al final de esta lectura serán complementarios) son el "Progreso de la ciencia" según Kuhn y el " Epistemología ".

Progreso de la ciencia según Thomas Kuhn

Thomas Kuhn en su obra más famosa afirma que "la ciencia pasa cíclicamente por algunas fases indicativas de su funcionamiento".[5][6] Según Kuhn, "la ciencia es paradigmática", y la demarcación entre ciencia y pseudociencia se remonta a la existencia de un "'paradigma'". La evolución del progreso científico se asimila a "una curva continua que sufre discontinuidad en los cambios de paradigma". Por ejemplo, en la fase 2 de los Paradigmas de Kuhn, denominada 'Ciencia Normal' , los científicos son vistos como solucionadores de problemas, que trabajan para mejorar la concordancia entre el paradigma y la naturaleza.

Esta fase, de hecho, se sustenta en un conjunto de principios básicos dictados por el paradigma, que no son cuestionados pero a los que, efectivamente, se les encomienda la tarea de indicar las coordenadas de las obras por venir. En esta fase se desarrollan los instrumentos de medida con los que se realizan los experimentos, se elaboran la mayoría de los artículos científicos y sus resultados constituyen un crecimiento significativo del conocimiento científico. En la fase científica normal se conseguirán tanto los éxitos como los fracasos; Kuhn llama a las fallas "anomalías" o "eventos que van en contra del paradigma".

Como buen solucionador de problemas, el científico intenta resolver estas anomalías.

Kuhn, sin embargo, divide la evolución de un paradigma en "cinco fases"; este es un proceso fundamental para Masticationpedia, pero para estar en sintonía con el proyecto, nos limitaremos a describir las dos fases más significativas:

 
  • Fase 4, o la Crisis del paradigma
    Como consecuencia de la crisis, se crearán diferentes paradigmas durante este período. Estos nuevos paradigmas, por tanto, no surgirán de los resultados alcanzados por la teoría anterior, sino del abandono de los esquemas preestablecidos del paradigma dominante.
    Siguiendo este camino, en Masticationpedia, se discutirá la 'crisis del paradigma de rehabilitación masticatoria' revisando teorías, teoremas, axiomas, escuelas de pensamiento y los Criterios de Diagnóstico de Investigación y luego el foco pasará a la fase 5.
 
  • Fase 5, o la 'Revolución científica'
    La fase 5 trata de la revolución (científica). En el período de extraordinarias actividades científicas, se abrirá una discusión dentro de la comunidad científica sobre qué nuevo paradigma aceptar. Pero no será necesariamente el paradigma más "verdadero" o más eficiente que salga a la luz, sino el que podrá captar el interés de un número suficiente de científicos y ganarse la confianza de la comunidad científica.
    Los paradigmas que participan en este choque, según Kuhn, no comparten nada, ni siquiera las bases y, por tanto, no son comparables (son "inconmensurables"). El paradigma se elige, como se dijo, sobre una base socio-psicológica o biológica (los científicos jóvenes reemplazan a los mayores). La batalla entre paradigmas resolverá la crisis, se nombrará el nuevo paradigma y la ciencia volverá a la Fase 1.
    Por el mismo principio de la Fase 4, Masticationpedia propondrá, en el capítulo titulado Ciencia extraordinaria , un 'nuevo modelo paradigmático en el campo de la rehabilitación del Sistema Masticatorio' discutiendo sus principios, motivaciones, clínicas científicas experiencias y, sobre todo, un “cambio radical” en el campo del diagnóstico médico. Este cambio se basa esencialmente en la 'Inferencia del sistema' , más que en la Inferencia de síntomas, dando principalmente valor absoluto a la objetividad de los datos.

Es casi obvio que la filosofía científica kuhniana prefiere la disciplina, ya que un genetista notará mejor una anomalía en el paradigma genómico que un neurofisiólogo. Ahora bien, este concepto parecería estar en contraste con la evolución epistemológica de la ciencia, por lo que es mejor detenerse un minuto en él en detalle.

Epistemología

El cisne negro simboliza uno de los problemas históricos de la epistemología: si todos los cisnes que hemos visto hasta ahora son blancos, ¿podemos decidir que todos los cisnes son blancos?
En serio?
Black Swan (Cygnus atratus) RWD.jpg
 
Duck-Rabbit illusion.jpg
Kuhn usó la ilusión óptica para demostrar cómo un cambio de paradigma puede hacer que una persona vea la misma información de una manera completamente diferente: ¿qué animal es el que está aquí al lado?
Seguro?

'Epistemología' (del griego ἐπιστήμη, epistème , "cierto conocimiento" o "ciencia", y λόγος, logos , "habla") es la rama de la filosofía que se ocupa de la condiciones bajo las cuales se puede obtener el conocimiento científico y los métodos para lograrlo.[7] El término indica específicamente aquella parte de la gnoseología que estudia los fundamentos, validez y límites del conocimiento científico. En los países de habla inglesa, el concepto de epistemología se utiliza principalmente como sinónimo de gnoseología o teoría del conocimiento, la disciplina que se ocupa del estudio del conocimiento.

Por cierto, el problema básico de la epistemología actual, como en la época de Hume, sigue siendo el de la verificabilidad.[8][9]

La paradoja de Hempel nos dice que cada cisne blanco avistado confirma que los cuervos son negros[10]; es decir, `` cada ejemplo que no contrasta con la teoría confirma una parte de ella :


According to the objection of falsifiability, instead, no theory is ever true because, while there are only a finite number of experiments in favour, there is also theoretically an infinite number that could falsify it.[11]

But it’s not all so obvious...

...because the very concept of epistemology meets continuous implementations, like in medicine:

  • :
    In medicine, for example, to confirm an experiment, a series of data coming from laboratory instruments or from surveys, the "Statistical Inference" is used, and in particular a famous value called "significance test" (). Well, even this concept, now part of the researcher's genesis, is wavering. In a recent study, attention was focused on a "Campaign" conducted on "Nature" against the concept of "significance tests"[12].
    With over 800 signatories supporting important scientists, this "campaign" can be considered an important milestone and a "Silent Revolution" in statistics on logical and epistemological aspects[13][14][15]. The campaign criticizes the too simplified statistical analyses that can still be found in many publications to date.
    This eventually led to a discussion, sponsored by the American Statistical Association, which spawned a special issue of "The American Statistician Association" titled "Statistical Inference in the 21st Century: A World Beyond p <0,05", containing 43 articles by forward-looking statisticians[16]. The special question proposes both new ways to signal the importance of research results beyond the arbitrary threshold of a P-value, and some guides to conduct of research: the researcher should accept uncertainty, be reflective, open and modest in his/ her statements[16]. Future will show whether or not those attempts to statistically better support science beyond the significance tests will be reflected in future publications[17]. In this field too, we are on the same wavelength as the Progress of Science according to Kuhn, in that we are talking about the re-modulation of some descriptive statistical contents within the scope of disciplinarity.
  • Interdisciplinarity:
    In science policy, it is generally recognized that science-based problem solving requires interdisciplinary research (IDR), as proposed by the EU project called Horizon 2020[18]. In a recent study, the authors focus on the question why researchers have cognitive and epistemic difficulties in conducting IDR. It is believed that the loss of philosophical interest in the epistemology of interdisciplinary research is due to a philosophical paradigm of science called "Physics Paradigm of Science", which prevents recognition of important IDR changes in both the philosophy of science and research.
    The proposed alternative philosophical paradigm, called "Engineering Paradigm of Science", makes alternative philosophical assumptions about aspects such as the purpose of science, the character of knowledge, the epistemic and pragmatic criteria for the acceptance of knowledge and the role of technological tools. Consequently, scientific researchers need so-called metacognitive scaffolds to assist them in the analysis and reconstruction of how "knowledge" is constructed in different disciplines.
    In interdisciplinary research, metacognitive scaffolds help interdisciplinary communication analyse and articulate how the discipline builds knowledge[19][20]

Anomaly vs. Interdisciplinarity

Given the above, on a superficial view of the epistemic evolution of the Science, the two aspects of disciplinarity ("Physics Paradigm of Science", highlighting the anomaly) and Interdisciplinary ("Engineering Paradigm of Science", metacognitive scaffold), might seem to be in conflict with each other; in reality, however, as we are just going to see right in this chapter, they are two sides of the same coin because both tend to generate "Paradigmatic Innovation" without any conflict at all.

Now we could conclude that the "Innovations" are already "Progress of Science" in themselves, as stated in the article "Scientific basis of dentistry" by Yegane Guven, in which the effect of biological and digital revolutions is considered on dental education and daily clinical practice, such as personalized regenerative dentistry, nanotechnologies, virtual reality simulations, genomic information and stem cell studies.[21] The innovations mentioned by Guven are obviously to be considered as technological and methodological in nature; however, the Progress of Science does not move forward with this kind of Innovations, which are called "Incremental Innovations" and "Radical Innovations", but it occurs substantially through "Paradigmatic Innovations".

In the strictest sense of the phrase, "Paradigmatic Innovations" are essentially a change of thought and awareness that pervades the whole of humanity, starting from different social strata, from the Copernican scientific revolution to the current trend of Stochastic approach to the biological phenomenon[22].

In this epistemological context (in addition to other initiatives such as the Research Diagnostic Criteria in the field of the Temporomandibular Disorders — RDC/TMDs), of the Evidence Based Medicine (and other), the Masticationpedia project inserts itself in order to highlight the dialectics dynamism about the progress of the masticatory rehabilitation science. Masticationpedia tends, moreover, to highlight the anomalies that inevitably stimulate a change of thought and therefore a "Paradigmatic Innovation".

Before proceeeding, it could be appropriate to observe a very concrete and significant case.

Malocclusion

Malocclusion: it literally means a bad (malum, in Latin) closure of the dentition[23]. The closure is easy to understand, we believe, but the epithet "bad" must be understood with care as well, because it is not as simple as it seems.

To briefly grasp the concept, in this first introductory reading we will try to present a simple but highly debatable question that involves a series of other questions in the field of masticatory rehabilitation and especially in orthodontic disciplines: what is "Malocclusion"? Bear in mind that in 2019, a Pubmed query about this term returned a result of "only" 33,309 articles[24], which says it all about the hypothetical terminological agreement on the subject; and, therefore, very meaningful conclusions could be drawn every now and then from these articles, such as the ones we reproduce in full from an article by Smaglyuk and collaborators, a somewhat "sensational" article that deals with the interdisciplinary approach in the diagnosis of malocclusions[25]:

«The diagnostics, treatment tactics and prevention of dento-facial anomalies and deformations should be considered in the context of the integrity of the child's unformed organism, the interdependence of the form and functions of its organs and systems»

Another noteworthy fact is that if in the same 2019 Pubmed was questioned on interdisciplinarity in the diagnosis of malocclusions, the result dropped drastically to just four articles[26].

These premises to the "Malocclusion” question indicate, on one hand, an alert about anomalies that tend to activate Kuhn phase 4 and, on the other, a bifurcation in the epistemic choice on the subject: one that generates Incremental Innovations (others 33,309 articles, perhaps) and another that prefers a new gnoseological path of "Paradigmatic Innovation”.

Let’s try to approach part of the concept that considers the "Paradigmatic Innovation” as essential, asking ourselves for example:

Figura 1a:
Patient with malocclusion, open bite and right posterior crossbite who in rehabilitation terms should be treated with orthodontic therapy and / or orthognathic surgery.

What does "Malocclusion" mean?

We will answer this question by reporting a clinical case of evident “Malocclusion”.

Patient is with an occlusion that orthodontists call “Malocclusion” because it has a posterior unilateral crossbite and anterior openbite[27]; it is a malocclusion that can be treated with a fixed orthodontic therapy and possibly in combination with an orthognathic intervention[28]. Crossbite is another element of disturbance in normal occlusion because of which it is obligatorily treated together with the openbite[29][30][31].

It is self-evident that an observer with a deterministic mindset facing a phenomenon of such evident occlusal incongruity considers crossbite and openbite the cause of malocclusion (cause/effect) or vice versa; and it is obvious, as well, that the observer recommends an orthodontic treatment to restore a “Normocclusion”. This way of reasoning means that the model (masticatory system) is “normalized to occlusion”; and if read backwards, it means that the occlusal discrepancy is the cause of malocclusion and, therefore, of disease of the Masticatory System. (Figure 1a).

But let's hear what the two players say, the dentist and the patient, in the informative dialogue.

Figure 1b: Motor evoked potential from electrical transcranial stimulation of the trigeminal roots. Note the structural symmetry calculated by the peak-to-peak amplitude on the right and left masseters.
     The dentist tells the patient that he is suffering from severe malocclusion and that it should be treated to improve its aesthetics and chewing function. The patient, however, replies firmly: «No way, I haven't the slightest idea to do it at all, doctor, because I might even have an unrepresentative smile, but I eat very well.»
The dentist’s reply is ready, so the practitioner insists by saying: «but you have a serious malocclusion with an openbite and a unilateral posterior crossbite, you should already have problems with bruxism and swallowing, as well as posture.»
The patient closes the confrontation in a decisive way: «absolutely false: I chew very well, I swallow very well and at night I snore alot so I don’t grind; besides, I’m a sportsman and I don’t have any postural disturbance».

Now the conclusion remains very critical because we might be finding ourselves in front of a verbal language of the patient which is misleading because it is not specific and does not respond to a detailed physiopathogenetic knowledge of the occlusal state; or, paradoxically, we are otherwise facing a machine language converted into verbal language which guarantees the integrity of the system. At this point the situation is truly embarrassing because neither the patient nor the observer (dentist) will be able to say with certainty that the System is in a “Malocclusion” state.

Figure 1c: Mandibular reflex evoked by percussion of the chin through a triggered neurological hammer.
Note the functional symmetry calculated by the peak-to-peak amplitude on the right and left masseters.

It is precisely at this moment that one remembers the criticism of the American Statistician Association titled “Statistical inference in the 21st century: A World Beyond p <0.05”, which urges the researcher to accept uncertainty, be sensible reflective, open and modest in his statements[16]: which basically translates into a search for interdisciplinarity.

Figure 1d: Mechanical silent period evoked by percussion of the chin through a triggered neurological hammer. Note the functional symmetry calculated on the integral area of the right and left masseters.

Interdisciplinarity, in fact, could answer such a complex question; but it is nonetheless necessary to interpret the biological phenomenon of "“Malocclusion”" with a stochastic forma mentis of which we will discuss in detail later.

A stochastic observer may observe that there is a low probability that the patient, at the moment , is in a state of occlusal disease, as the patient's natural language indicates ideal psychophysical health; he/she then concludes that the occlusal discrepancy could not be a cause of neuromuscular and psychophysical functional disorder. In this case, therefore, the Masticatory System can not only be normalized to the occlusion only, but a more complex model is needed too, so it has to be normalized to the Trigeminal Nervous System. The patient was then served a series of trigeminal electrophysiological tests to assess the integrity of his/her Trigeminal Nervous System in these “"Malocclusion”" clinical conditions.

We can see the following output responses, which we report directly in figures 1b, 1c and 1d (with explanation in the caption, to simplify the discussion). These tests and their description by now should only be considered as “Conceptual Rationale” for the “Malocclusion” question; later they will be widely described and their analysis detailed in the specific chapters. It can already be noted in this first descriptive approach to the masticatory phenomenon that there is an evident discrepancy between the occlusal state (which at first would support the orthodoxy of classical orthodontics in considering it as “Malocclusive State”) and the neurophysiological data indicating incredible synchronization and perfect symmetry of the trigeminal reflexes.

These results can be attributed to anything less than a "malocclusion": we are obviously in front of an error of the logic Language in medicine, in this case it is in fact more appropriate to talk about...

Occlusal dysmorphism and not Malocclusion (which, as we shall see a little further on, is quite another thing)

Conclusion

Even before drawing conclusions, conceptual clarity must be made on some fundamental points which of course will be treated in detail in the specific chapters of Masticationpedia.

The Masticatory System should be considered as a “Complex System[32], not as a Biomechanical System focused exclusively on dental occlusion, because in this sense the “Occlusion” is nothing more than a subset of the Complex System interacting with the other subsets, such as periodontal receptors, neuromuscular spindles, recruitment of motor units, central nervous system, temporomandibular joint, etc., to give shape to an “Emerging Behaviour”, the masticatory one.

The peculiarity of this concept is that it is not possible to interpret or predict the “Emerging Behaviour” of a System by extracting objective data from a single subset. Instead, the integrity of the System must be quantified in its entirety, and only then can a segmentation of the whole be attempted to make an analytical description of the node itself. There are very important intellectual and scientific movements that are engaging with this issue; in this regard, the extraordinary work of Prof. Kazem Sadegh-Zadeh: Handbook of Analytic Philosophy of Medicine comes to mind.[33]

In the presented case, the question is resolved in the following language logic:

The subsets of the Masticatory System (teeth, occlusion, Temporomandibular joints, muscles, etc.) are in a state of "Coherence” with the Central Trigeminal Nervous System (see figures 1b, 1c and 1d), so the term “Malocclusion” cannot be used, the phrase “Occlusal Dismorphism” should be considered instead.
«This does not mean abolishing prosthetic, orthodontic and orthognathic masticatory rehabilitation treatments: on the contrary, this forma mentis tends to restore medical knowledge to dental rehabilitation disciplines, as well as offering an alternative to the scientific reductionism that converges in a deterministic interpretation of the biological phenomenon.»

Going beyond the specialist perimeters of the disciplines, as previously reported on interdisciplinarity, helps expanding the diagnostic and therapeutic models as it can be seen in the clinical Case in which a patient was treated with the OrthoNeuroGnathodontic method is reported.

In this way, an overall view of the entire Masticatory System is presented in order to gather the aesthetic and functional-neurophysiological components together to determine “Occlusal Stability” and to avoid “Relapses”, especially in orthodontic and orthognathic treatments.[34][35]

These are just some of the topics that will be covered extensively both in this chapter and in what we call “Extraordinary Science”. Meanwhile, in a fitting diversion our colourful friend Linus Sapiens, the little yellow man on the left, asks us:

Question 2.jpg
«What do we mean by “Complex Systems” when we are talking about masticatory functions?»
Bibliography & references
  1. Latín para "desde el principio"
  2. Heft MW, Fox CH, Duncan RP, «Assessing the Translation of Research and Innovation into Dental Practice», in JDR Clin Trans Res, 2019.
    DOI:10.1177/2380084419879391 
  3. «Exposure Science in the 21st Century. A Vision and a Strategy», Committee on Human and Environmental Exposure Science in the 21st Century; Board on Environmental Studies and Toxicology; Division on Earth and Life Studies; National Research Council..
    ISBN: 0-309-26468-5 
  4. Liu L, Li Y, «The unexpected side effects and safety of therapeutic monoclonal antibodies», in Drugs Today, 2014, Barcellona.
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  5. Thomas Samuel Kuhn (Cincinnati, 18 julio 1922 – Cambridge, 17 junio 1996) fue un filósofo de la ciencia estadounidense.
    Ver Treccani, Kuhn, Thomas Samuel. Wikipedia, Thomas Kuhn.
  6. Kuhn Thomas S, «The Structure of Scientific Revolutions», Univ. of Chicago Press, 2012, Chicago.
    ISBN: 9780226458113 
  7. Se cree que el término fue acuñado por el filósofo escocés James Frederick Ferrier en sus `` Institutos de metafísica . (p.46), of 1854; si es Internet Encyclopedia of Philosophy, James Frederick Ferrier (1808—1864). Wikipedia
  8. David Hume (Edimburgh, 7 may 1711 – Edimburgh, 25 august 1776) fue un filósofo escocés. Se le considera el tercero y quizás el más radical de los empiristas británicos, después del inglés John Locke y el angloirlandés George Berkeley.
  9. Srivastava S, «Verifiability is a core principle of science», in Behav Brain Sci, Cambridge University Press, 2018, Cambridge.
    DOI:10.1017/S0140525X18000869 
  10. Aquí, obviamente, nos referimos a la conocida paradoja llamada "de los cuervos", o "de los cuervos negros", formulada por el filósofo y matemático Carl Gustav Hempel, mejor explicado en el artículo de Wikipedia Raven paradox:
    Si es Good IJ, «The Paradox of Confirmation», in Br J Philos Sci, 1960 – in Vol. 11. 
  11. Evans M, «Measuring statistical evidence using relative belief», in Comput Struct Biotechnol J, 2016.
    DOI:10.1016/j.csbj.2015.12.001 
  12. Amrhein V, Greenland S, McShane B, «Scientists rise up against statistical significance», in Nature, 2019.
    DOI:10.1038/d41586-019-00857-9 
  13. Rodgers JL, «The epistemology of mathematical and statistical modeling: a quiet methodological revolution», in Am Psychol, 2010.
    DOI:10.1037/a0018326 
  14. Meehl P, «The problem is epistemology, not statistics: replace significance tests by confidence intervals and quantify accuracy of risky numerical predictions», 1997. , in eds Harlow L. L., Mulaik S. A., Steiger J. H., What If There Were No Significance Tests? - editors. (Mahwah: Erlbaum, 393–425. [Google Scholar]
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    DOI:10.1080/00031305.2019.1583913 
  17. Dettweiler Ulrich, «The Rationality of Science and the Inevitability of Defining Prior Beliefs in Empirical Research», in Front Psychol, 2019.
    DOI:10.3389/fpsyg.2019.01866 
  18. European Union, Horizon 2020
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