Paradigm shift | EPFL Graph Search

A paradigm shift is a fundamental change in the basic concepts and experimental practices of a . It is a concept in the philosophy of science that was introduced and brought into the common lexicon by the American physicist and philosopher Thomas Kuhn. Even though Kuhn restricted the use of the term to the natural sciences, the concept of a paradigm shift has also been used in numerous non-scientific contexts to describe a profound change in a fundamental model or perception of events. Kuhn presented his notion of a paradigm shift in his influential book The Structure of Scientific Revolutions (1962). Kuhn contrasts paradigm shifts, which characterize a Scientific Revolution, to the activity of normal science, which he describes as scientific work done within a prevailing framework or paradigm. Paradigm shifts arise when the dominant paradigm under which normal science operates is rendered incompatible with new phenomena, facilitating the adoption of a new theory or paradigm. As on

Towards patient-tailored interventions for stroke recovery: graph theoretical approaches and modeling of non-invasive brain stimulation

Giorgia Giulia Evangelista

Stroke is a disease that causes the death of precious brain cells that will never grow back and which will affect one in four humans at some point in their life. While therapies and treatments for this debilitating condition are fairly standard, their outcomes are highly heterogeneous, with deficits all too often leading to permanent disability. These unsatisfactory outcomes point to the need for a paradigm shift towards precision medicine, where therapies and treatments are tailored to individual patients. This in turn requires a better understanding of the mechanisms underlying post-stroke impairment and recovery. Recent technological innovations provide an unprecedented opportunity to acquire a detailed picture of the anatomy and electrophysiology of the human brain non-invasively. Therefore, we apply multimodal methodologies to investigate the inner workings of the stroke-affected brain with a view to establishing biomarkers and creating stratifications that maximize the effectiveness of stroke therapy by making it personalized.In the first part of this thesis, network-theoretic models of the brain known as connectomes are created, under the assumption that these provide sufficiently detailed information about the individual patient to inform personalized recommendations. In particular, we leverage existing knowledge about how brain networks are organized into specialized modules connected by a "rich-club" of hubs. In a novel contribution to the field of connectomics, we combine these connectomes with detailed images of the lesion to obtain a network-theoretic lesion profile and a map of the non-lesioned part of the network, which we expect to be a better reflection of true brain connectivity. Using this methodology, we establish that the rich-club, in addition to being a source of network robustness, is also a source of vulnerability in that attacks against it lead to poor behavioral outcomes disproportionate to the size of the attacks.The creation of in-silico simulation of individual patients presents a great opportunity to quickly experiment with treatments, making it a potential game-changer in medical research. However, current technology is not able to faithfully capture the complexity of a whole human brain. The complex brain abnormalities inherent to stroke only add to the difficulty of the challenge. Any models one might wish to create must strike a balance between technological feasibility and sensitivity to inter-patient variability across a large parameter space. In the second part of this thesis, we investigate whether one major source of inter-patient variability, namely the size and location of the lesion, induces substantial variability in the effects of non-invasive brain stimulation to be included as factors in the design of stimulation protocols. Based on our modeling of the stimulation, personalizing stimulation protocols by taking the lesion into account produces little added value, except possibly when one is targeting brain areas close to the lesion and the lesion is significantly large.The proposed studies represent a step of the march towards precision medicine, by examining sources of variability in stroke patients and by associating them with variability in some outcomes of interest. Each step of this march brings stroke therapy farther from the status quo of homogeneous treatments and heterogeneous outcomes and closer to the ideal of heterogeneous treatments and homogeneously positive outcomes.

EPFL2022

Validation of the Mass-Extraction-Window for Quantitative Methods Using Liquid Chromatography High Resolution Mass Spectrometry

Anne-Laure Gassner, Laure Menin, Bertrand Rochat

A paradigm shift is underway in the field of quantitative liquid chromatography-mass spectrometry (LC-MS) analysis thanks to the arrival of recent high-resolution mass spectrometers (HRMS). The capability of HRMS to perform sensitive and reliable quantifications of a large variety of analytes in HR-full scan mode is showing that it is now realistic to perform quantitative and qualitative analysis with the same instrument. Moreover, HR-full scan acquisition offers a global view of sample extracts and allows retrospective investigations as virtually all ionized compounds are detected with a high sensitivity. In time, the versatility of HRMS together with the increasing need for relative quantification of hundreds of endogenous metabolites should promote a shift from triple-quadrupole MS to HRMS. However, a current "pitfall" in quantitative LC-HRMS analysis is the lack of HRMS-specific guidance for validated quantitative analyses. Indeed, false positive and false negative HRMS detections are rare, albeit possible, if inadequate parameters are used. Here, we investigated two key parameters for the validation of LC-HRMS quantitative analyses: the mass accuracy (MA) and the mass-extraction-window (MEW) that is used to construct the extracted-ion-chromatograms. We propose MA-parameters, graphs, and equations to calculate rational MEW width for the validation of quantitative LC-HRMS methods. MA measurements were performed on four different LC-HRMS platforms. Experimentally determined MEW values ranged between 5.6 and 16.5 ppm and depended on the HRMS platform, its working environment, the calibration procedure, and the analyte considered. The proposed procedure provides a fit-for-purpose MEW determination and prevents false detections.

Amer Chemical Soc2016

Financing Biomedical Ventures - Myths and Realities

Jeffrey Scott Behrens

Angel funding is an important source of capital for startup ventures (J. Sohl 2019), providing a similar level of capital as institutional venture capital (OECD 2011). But angel funding is challenging to study due to the informal nature of the activity. A common paradigm for new venture funding argues that new ventures initially fund their activities with angel investment and then, as they show success, make progress to commercialization and de-risk core venture propositions, ventures transition to more professional institutional (venture capital) funding. A belief in this paradigm can strongly influence early venture creation activities, and assumptions about the later availability of capital from institutional venture capital underpin many startup business plans. However, the literature exploring this phenomenon is very sparse, and the question of the relationship of angel to venture funding transition has rarely been studied. By analyzing a large and robust dataset, this thesis advances the understanding of the actual behavior of investors and the impact this early behavior, and the funding choices involved, have on company outcomes. This thesis also explores a novel form of venture investing and places it into a broader context of new venture funding that may help explain some of the key observations discussed. These fundamentally empirical studies examine the nature/reality of important entrepreneurial phenomena of interactions between angel and venture funding in novel ways, pose questions, and identify a set results that point to a potential market failure. Attempts are made to understand these results and place them into the contexts of both research theory and a broader understanding of entrepreneurial behavior; there certainly remain a set of unanswered questions and potential fruitful directions for future research.

EPFL2020

Towards patient-tailored interventions for stroke recovery: graph theoretical approaches and modeling of non-invasive brain stimulation

Giorgia Giulia Evangelista

EPFL2022