Pharma-Nutrition: a pharma perspective. View how the pharmaceutical drug development model can and should be combined with the nutrition field to optimally implement personalized healthcare.
2014 07-08 Selectbio Biomarkers 2014, CambridgeAlain van Gool
The document discusses biomarkers in personalized healthcare from discovery to clinical diagnostics, providing an overview of the speaker's experience in academia, pharmaceutical industry, and applied research focusing on biomarkers and omics technologies. It also describes the Radboud University Medical Center's focus on personalized healthcare through its technology centers and biomarker research on conditions like metabolic syndrome. The discussion emphasizes how biomarkers are evolving from diagnosis to tools that enable personalized and participatory healthcare approaches.
The document summarizes several current research projects taking place on a university campus:
1. The 'NorthGell' project is developing new hydrogel-based products that can fill skin imperfections or gradually release pharmaceuticals to prevent scarring.
2. The 'Twincer' is a dry powder inhaler being developed to effectively deliver relatively high drug doses. It is being tested to determine suitable medications.
3. The 'Sprint@Work' project aims to develop sensor technologies to measure employee performance and develop interventions to improve physical and cognitive functioning in the workplace.
Translational research aims to bridge the gap between basic science discoveries and clinical applications to improve human health. It involves translating findings from laboratory and preclinical studies into potential new diagnostics and treatments for patients. There are multiple phases of translational research, including T1 which moves basic discoveries into clinical applications, and T2 which provides evidence of a discovery's value in a clinical setting. Effective translation is needed to realize the benefits of increased biomedical research funding and requires tools like biomarkers to facilitate predicting efficacy and safety across species.
The Translational Medicine Ontology: Driving personalized medicine by br...Michel Dumontier
The Translational Medicine Ontology provides terminology that bridges diverse areas of translational medicine including hypothesis management, discovery research, drug development and formulation, clinical research, and clinical practice. Designed primarily from use cases, the ontology consists of essential terms that are mapped to other ontologies. It serves as a global schema for data integration while simultaneously facilitating the formulation of complex queries across heterogeneous sources. We demonstrate the utility of the ontology through question answering over a prototype knowledge base composed of sample patient data integrated with linked open data. This work forms a basis for the development of a computational platform for managing information relevant to personalized medicine.
2021 03-25 11th World Clinical Biomarkers & Companion Diagnostics, Alain van ...Alain van Gool
Closing keynote of a 3-day conference on clinical biomarkers and companion diagnostics, organised by Hanson Wade, outlining the power of omics approaches in healthcare and translation of inovations to impact.
2020 08-28 SensUs Event 2020 keynote, Eindhoven, Alain van GoolAlain van Gool
Closing keynote for international students participating in the SensUs Event 2020, where they designed and created a novel sensor for drug level monitoring in epilepsy treatment. Lecture outlined innovations in biomarkers in personalized health(care).
Clinical Research is a most knowledge-intensive and interesting field in the pharmaceutical industry. There are more than 2, 50,000 positions unemployed in global Pharmaceutical industry.
The document discusses using semantic web technologies to create a Translational Medicine Ontology and Knowledge Base (TMOKB) for integrating personalized medicine data. It describes how the TMOKB links terms from existing ontologies and data sources to answer questions about Alzheimer's disease genes, biomarkers, drug repurposing opportunities, and clinical trials. The TMOKB demonstrates how a high-level ontology can connect specialized domain ontologies and data to provide integrated answers across personalized medicine.
2014 07-08 Selectbio Biomarkers 2014, CambridgeAlain van Gool
The document discusses biomarkers in personalized healthcare from discovery to clinical diagnostics, providing an overview of the speaker's experience in academia, pharmaceutical industry, and applied research focusing on biomarkers and omics technologies. It also describes the Radboud University Medical Center's focus on personalized healthcare through its technology centers and biomarker research on conditions like metabolic syndrome. The discussion emphasizes how biomarkers are evolving from diagnosis to tools that enable personalized and participatory healthcare approaches.
The document summarizes several current research projects taking place on a university campus:
1. The 'NorthGell' project is developing new hydrogel-based products that can fill skin imperfections or gradually release pharmaceuticals to prevent scarring.
2. The 'Twincer' is a dry powder inhaler being developed to effectively deliver relatively high drug doses. It is being tested to determine suitable medications.
3. The 'Sprint@Work' project aims to develop sensor technologies to measure employee performance and develop interventions to improve physical and cognitive functioning in the workplace.
Translational research aims to bridge the gap between basic science discoveries and clinical applications to improve human health. It involves translating findings from laboratory and preclinical studies into potential new diagnostics and treatments for patients. There are multiple phases of translational research, including T1 which moves basic discoveries into clinical applications, and T2 which provides evidence of a discovery's value in a clinical setting. Effective translation is needed to realize the benefits of increased biomedical research funding and requires tools like biomarkers to facilitate predicting efficacy and safety across species.
The Translational Medicine Ontology: Driving personalized medicine by br...Michel Dumontier
The Translational Medicine Ontology provides terminology that bridges diverse areas of translational medicine including hypothesis management, discovery research, drug development and formulation, clinical research, and clinical practice. Designed primarily from use cases, the ontology consists of essential terms that are mapped to other ontologies. It serves as a global schema for data integration while simultaneously facilitating the formulation of complex queries across heterogeneous sources. We demonstrate the utility of the ontology through question answering over a prototype knowledge base composed of sample patient data integrated with linked open data. This work forms a basis for the development of a computational platform for managing information relevant to personalized medicine.
2021 03-25 11th World Clinical Biomarkers & Companion Diagnostics, Alain van ...Alain van Gool
Closing keynote of a 3-day conference on clinical biomarkers and companion diagnostics, organised by Hanson Wade, outlining the power of omics approaches in healthcare and translation of inovations to impact.
2020 08-28 SensUs Event 2020 keynote, Eindhoven, Alain van GoolAlain van Gool
Closing keynote for international students participating in the SensUs Event 2020, where they designed and created a novel sensor for drug level monitoring in epilepsy treatment. Lecture outlined innovations in biomarkers in personalized health(care).
Clinical Research is a most knowledge-intensive and interesting field in the pharmaceutical industry. There are more than 2, 50,000 positions unemployed in global Pharmaceutical industry.
The document discusses using semantic web technologies to create a Translational Medicine Ontology and Knowledge Base (TMOKB) for integrating personalized medicine data. It describes how the TMOKB links terms from existing ontologies and data sources to answer questions about Alzheimer's disease genes, biomarkers, drug repurposing opportunities, and clinical trials. The TMOKB demonstrates how a high-level ontology can connect specialized domain ontologies and data to provide integrated answers across personalized medicine.
What advantages does Cinderella’s approach bring? Important advantages are illustrated in this presentation, including renouncing the profit principle, restarting the interrupted development of drugs considered to have insufficient potential for the generation of profits and bringing new drugs to patients for an affordable price by using a scientifically and economically sound study design
Are we ready for disruption in Translational Research through Digital Medicine?Ashish Atreja, MD, MPH
This is the slide deck that was presented at Translational Science 2016. Touches upon evidence generation as one of the most desired but expensive process in medical science. Provides examples of how Social Media, medical apps, quantified self movement are leading to patient generated data that can disrupt evidence generation process.
Development of Translational Medicine at Univ. of Medicine & Pharmacy (UMP), ...Thai Nguyen PeterTigr
UMP is now taking the new challenge in developing modern biomedical research to align our scientific programs with the international medical community, and importantly, to harness the advancements of biological sciences for medical services, via translational research, for unmet medical illnesses of the Vietnamese patients.
This document discusses translational pharmacology, which aims to translate biomedical research findings into improved patient care and treatment. It involves applying laboratory research to clinical practice through a "bench to bedside" approach. The objectives of translational pharmacology are to discover disease origins and biomarkers, and develop new diagnostics and therapies more quickly. While powerful tools now exist, hurdles remain, including scientific, ethical, regulatory, financial and lack of investigators. Translational pharmacology seeks to bridge specialized fields and provide better pre-clinical results and dosing regimens to maximize patient benefit.
Guideline on patient safety and well being in clinical trialsTrialJoin
Patient safety is and should be the number one priority in clinical research. Human participants in a clinical trial are necessary in order to improve and develop new therapies for certain conditions and advance the understanding of how a condition can be treated. Such medical advancements wouldn’t be possible without human subjects as participants. However, even though we all know the importance of clinical trials in the advancement of medicine, most people still have some misconceptions regarding this topic.
The feeling of being treated as a ‘’guinea pig’’ and fear of potential risks and side effects are still common among patients who suffer from a certain condition. Such misinformation and misconceptions regarding clinical trials can unnecessarily prevent patients from finding a potential cure or relief, and can also decrease the number of enrolled patients in studies.
In order to clarify these misunderstandings, we’ve decided to tell you everything there is to know about patient safety in clinical trials. We hope that with this information we can help you to better understand patient safety in clinical trials so that you gain more insight and start considering clinical trials as valid options that can help you improve any condition.
Scope of Pharmacy and Clinical ResearchTejalPatil57
This document discusses the scope of pharmacy and clinical research. It begins by introducing various topics related to pharmaceutical sciences including pharmacy, pharmaceutical formulation, the pharma industry, and the scope of pharmacy. It then defines clinical research as the systematic study of safety and efficacy of new pharmaceutical products in humans. The document goes on to explain the different phases of clinical trials, from preclinical research through phases 0-IV. It emphasizes the importance of research for developing new diagnostic tests, drugs, surgical techniques, and combination treatments. Finally, it briefly mentions some job opportunities in clinical research.
tranSMART Community Meeting 5-7 Nov 13 - Session 1: Translational Drug Disco...David Peyruc
This document summarizes Andy Plump's presentation on translational drug discovery at Sanofi. It discusses two pillars of Sanofi's strategy: translational medicine and open innovation. Translational medicine focuses on human genetics, biology and disease to select targets and design clinical trials, moving from patients to research and back. Four success stories are highlighted: PCSK9 for heart disease, TrkA for pain, P53 for cancer, and glycolipids for Gaucher's disease. The presentation emphasizes applying lessons from human genetics and biology throughout the drug development process.
The document discusses key aspects of clinical trial strategy and design. It covers the different phases of clinical trials (Phase I, II, III) and provides guidance on optimizing trials at each phase. Phase I focuses on safety and dosing, Phase II evaluates efficacy and further safety, and Phase III confirms efficacy in a larger patient population. The document emphasizes establishing a detailed clinical development plan with timelines and costs to help guide development decisions and reduce risks.
This guideline provides evidence-based recommendations for the diagnosis and management of food allergy in patients of any age. It is based on three systematic reviews that examined the epidemiology, diagnosis, and management of food allergy. The reviews analyzed studies on the frequency and outcomes of food allergy in Europe, diagnostic tests for food allergy, and pharmacological and non-pharmacological treatments for food allergy reactions and long-term management. The guideline provides recommendations on diagnosis/evaluation, acute management, elimination diets, education and risk assessment, and oral food challenges.
June Lee, MD, Director of CTSI's Early Translational Research program, presents the goals and vision for the program. Learn more about June Lee at UCSF Profiles http://profiles.ucsf.edu/ProfileDetails.aspx?From=SE&Person=5208624
Health impairments can result in disability and changed work productivity imposing considerable
costs for the employee, employer and society as a whole. A large number of instruments exist to measure
health-related productivity changes; however their methodological quality remains unclear. This systematic review
critically appraised the measurement properties in generic self-reported instruments that measure health-related
productivity changes to recommend appropriate instruments for use in occupational and economic health practice.
1) Drug development involves multiple phases of clinical trials in humans (phases I-IV) to test dosing, safety and efficacy in an increasing number of patients before regulatory approval and market access.
2) Patient involvement in clinical research is important to ensure trials address patient priorities and perspectives on risk/benefit, endpoints, and trial design elements like inclusion criteria.
3) Key elements of a clinical trial protocol include type of comparisons, randomization, blinding, endpoints, inclusion/exclusion criteria, schedule of events, informed consent process, and patient reported outcomes.
This presentation explains the main features of medicines which will be developed and authorised via the adaptive pathways. It provides a definition of real world evidence and the caveats associated with the use and analysis of real world evidence in drug development.
The document discusses the importance of translational pharmacology in ensuring safe and effective dosing of drugs. It emphasizes using preclinical and clinical pharmacokinetic/pharmacodynamic studies and modeling throughout development to accurately translate dose levels between animal and human studies. This helps optimize dose selection for clinical trials and maximize the chances of demonstrating efficacy while avoiding toxicity. A case study illustrates how such an approach could have helped avoid failure of a Phase 2 oncology trial due to selecting a suboptimal dose.
Overview of the Patient-Centered Outcomes Research Institute (PCORI), how PCORI views Patient-Centered Outcomes Research and how this is related to PCORI’s major funding mechanisms.
Presentation given by Teresa Sardon from Anaxomics Biotech SL in the framework of the Emergence Forum Barcelona
Biocat organized the Barcelona Emergence Forum (April 10-11th, 2014, Congress Palace, Montjuïc) supported by the TRANSBIO SUDOE, a translational cooperation project dedicated to innovation in life sciences in South-West Europe. The Barcelona Emergence Forum contributed to bringing together Academics, Companies, Investment Entities, Technology Platforms and Technology Transfer Offices from Spain, France and Portugal to set up collaborative projects on Human Health & Agro-food Innovation.
More information at: http://www.b2match.eu/emergenceforum2014
Clinical trials are research studies involving human subjects that systematically investigate the safety and efficacy of new drugs. They aim to answer scientific questions and translate basic research results into better ways to prevent, diagnose, or treat diseases by generating safety and efficacy data for health interventions. Clinical trials are a key part of drug development and medical research.
1) The document summarizes key trends in multichannel marketing for pharmaceutical companies in China, emerging markets, and Japan. It finds that digital spending has increased across regions, with the highest levels in the Middle East, Latin America, and Japan. The most preferred digital channels are KOL webinars, HCP portals, and email marketing.
2) Respondents were split on whether channels should be implemented through single-brand or shared services approaches. In China, HCP portals and email were slightly preferred for shared services implementation.
3) Email was the most preferred channel for providing value-added services to HCPs, while KOL webinars were most preferred for brand promotion. Demonstrating
The document describes a client acquisition program called Right Financial Advisor. It is a web-based matching program that connects individual investors to vetted financial advisors. It aims to help advisors clone their best A and B clients while pruning poorer C and D clients. The program uses personality and financial needs questions to make better matches than competitors that rely solely on location or assets. It markets itself online and on social media to acquire new investors and advisors. Investors pay $35 to join while advisors pay $200 per month for unlimited introductions.
What advantages does Cinderella’s approach bring? Important advantages are illustrated in this presentation, including renouncing the profit principle, restarting the interrupted development of drugs considered to have insufficient potential for the generation of profits and bringing new drugs to patients for an affordable price by using a scientifically and economically sound study design
Are we ready for disruption in Translational Research through Digital Medicine?Ashish Atreja, MD, MPH
This is the slide deck that was presented at Translational Science 2016. Touches upon evidence generation as one of the most desired but expensive process in medical science. Provides examples of how Social Media, medical apps, quantified self movement are leading to patient generated data that can disrupt evidence generation process.
Development of Translational Medicine at Univ. of Medicine & Pharmacy (UMP), ...Thai Nguyen PeterTigr
UMP is now taking the new challenge in developing modern biomedical research to align our scientific programs with the international medical community, and importantly, to harness the advancements of biological sciences for medical services, via translational research, for unmet medical illnesses of the Vietnamese patients.
This document discusses translational pharmacology, which aims to translate biomedical research findings into improved patient care and treatment. It involves applying laboratory research to clinical practice through a "bench to bedside" approach. The objectives of translational pharmacology are to discover disease origins and biomarkers, and develop new diagnostics and therapies more quickly. While powerful tools now exist, hurdles remain, including scientific, ethical, regulatory, financial and lack of investigators. Translational pharmacology seeks to bridge specialized fields and provide better pre-clinical results and dosing regimens to maximize patient benefit.
Guideline on patient safety and well being in clinical trialsTrialJoin
Patient safety is and should be the number one priority in clinical research. Human participants in a clinical trial are necessary in order to improve and develop new therapies for certain conditions and advance the understanding of how a condition can be treated. Such medical advancements wouldn’t be possible without human subjects as participants. However, even though we all know the importance of clinical trials in the advancement of medicine, most people still have some misconceptions regarding this topic.
The feeling of being treated as a ‘’guinea pig’’ and fear of potential risks and side effects are still common among patients who suffer from a certain condition. Such misinformation and misconceptions regarding clinical trials can unnecessarily prevent patients from finding a potential cure or relief, and can also decrease the number of enrolled patients in studies.
In order to clarify these misunderstandings, we’ve decided to tell you everything there is to know about patient safety in clinical trials. We hope that with this information we can help you to better understand patient safety in clinical trials so that you gain more insight and start considering clinical trials as valid options that can help you improve any condition.
Scope of Pharmacy and Clinical ResearchTejalPatil57
This document discusses the scope of pharmacy and clinical research. It begins by introducing various topics related to pharmaceutical sciences including pharmacy, pharmaceutical formulation, the pharma industry, and the scope of pharmacy. It then defines clinical research as the systematic study of safety and efficacy of new pharmaceutical products in humans. The document goes on to explain the different phases of clinical trials, from preclinical research through phases 0-IV. It emphasizes the importance of research for developing new diagnostic tests, drugs, surgical techniques, and combination treatments. Finally, it briefly mentions some job opportunities in clinical research.
tranSMART Community Meeting 5-7 Nov 13 - Session 1: Translational Drug Disco...David Peyruc
This document summarizes Andy Plump's presentation on translational drug discovery at Sanofi. It discusses two pillars of Sanofi's strategy: translational medicine and open innovation. Translational medicine focuses on human genetics, biology and disease to select targets and design clinical trials, moving from patients to research and back. Four success stories are highlighted: PCSK9 for heart disease, TrkA for pain, P53 for cancer, and glycolipids for Gaucher's disease. The presentation emphasizes applying lessons from human genetics and biology throughout the drug development process.
The document discusses key aspects of clinical trial strategy and design. It covers the different phases of clinical trials (Phase I, II, III) and provides guidance on optimizing trials at each phase. Phase I focuses on safety and dosing, Phase II evaluates efficacy and further safety, and Phase III confirms efficacy in a larger patient population. The document emphasizes establishing a detailed clinical development plan with timelines and costs to help guide development decisions and reduce risks.
This guideline provides evidence-based recommendations for the diagnosis and management of food allergy in patients of any age. It is based on three systematic reviews that examined the epidemiology, diagnosis, and management of food allergy. The reviews analyzed studies on the frequency and outcomes of food allergy in Europe, diagnostic tests for food allergy, and pharmacological and non-pharmacological treatments for food allergy reactions and long-term management. The guideline provides recommendations on diagnosis/evaluation, acute management, elimination diets, education and risk assessment, and oral food challenges.
June Lee, MD, Director of CTSI's Early Translational Research program, presents the goals and vision for the program. Learn more about June Lee at UCSF Profiles http://profiles.ucsf.edu/ProfileDetails.aspx?From=SE&Person=5208624
Health impairments can result in disability and changed work productivity imposing considerable
costs for the employee, employer and society as a whole. A large number of instruments exist to measure
health-related productivity changes; however their methodological quality remains unclear. This systematic review
critically appraised the measurement properties in generic self-reported instruments that measure health-related
productivity changes to recommend appropriate instruments for use in occupational and economic health practice.
1) Drug development involves multiple phases of clinical trials in humans (phases I-IV) to test dosing, safety and efficacy in an increasing number of patients before regulatory approval and market access.
2) Patient involvement in clinical research is important to ensure trials address patient priorities and perspectives on risk/benefit, endpoints, and trial design elements like inclusion criteria.
3) Key elements of a clinical trial protocol include type of comparisons, randomization, blinding, endpoints, inclusion/exclusion criteria, schedule of events, informed consent process, and patient reported outcomes.
This presentation explains the main features of medicines which will be developed and authorised via the adaptive pathways. It provides a definition of real world evidence and the caveats associated with the use and analysis of real world evidence in drug development.
The document discusses the importance of translational pharmacology in ensuring safe and effective dosing of drugs. It emphasizes using preclinical and clinical pharmacokinetic/pharmacodynamic studies and modeling throughout development to accurately translate dose levels between animal and human studies. This helps optimize dose selection for clinical trials and maximize the chances of demonstrating efficacy while avoiding toxicity. A case study illustrates how such an approach could have helped avoid failure of a Phase 2 oncology trial due to selecting a suboptimal dose.
Overview of the Patient-Centered Outcomes Research Institute (PCORI), how PCORI views Patient-Centered Outcomes Research and how this is related to PCORI’s major funding mechanisms.
Presentation given by Teresa Sardon from Anaxomics Biotech SL in the framework of the Emergence Forum Barcelona
Biocat organized the Barcelona Emergence Forum (April 10-11th, 2014, Congress Palace, Montjuïc) supported by the TRANSBIO SUDOE, a translational cooperation project dedicated to innovation in life sciences in South-West Europe. The Barcelona Emergence Forum contributed to bringing together Academics, Companies, Investment Entities, Technology Platforms and Technology Transfer Offices from Spain, France and Portugal to set up collaborative projects on Human Health & Agro-food Innovation.
More information at: http://www.b2match.eu/emergenceforum2014
Clinical trials are research studies involving human subjects that systematically investigate the safety and efficacy of new drugs. They aim to answer scientific questions and translate basic research results into better ways to prevent, diagnose, or treat diseases by generating safety and efficacy data for health interventions. Clinical trials are a key part of drug development and medical research.
1) The document summarizes key trends in multichannel marketing for pharmaceutical companies in China, emerging markets, and Japan. It finds that digital spending has increased across regions, with the highest levels in the Middle East, Latin America, and Japan. The most preferred digital channels are KOL webinars, HCP portals, and email marketing.
2) Respondents were split on whether channels should be implemented through single-brand or shared services approaches. In China, HCP portals and email were slightly preferred for shared services implementation.
3) Email was the most preferred channel for providing value-added services to HCPs, while KOL webinars were most preferred for brand promotion. Demonstrating
The document describes a client acquisition program called Right Financial Advisor. It is a web-based matching program that connects individual investors to vetted financial advisors. It aims to help advisors clone their best A and B clients while pruning poorer C and D clients. The program uses personality and financial needs questions to make better matches than competitors that rely solely on location or assets. It markets itself online and on social media to acquire new investors and advisors. Investors pay $35 to join while advisors pay $200 per month for unlimited introductions.
+ Overview of MOBILE EVOLUTION AND DEVELOPMENT OF THE INTERNET.
+ MOBILE INTERNET: TRENDS AND GROWTH
+ BENEFITS OF THE MOBILE INTERNET
+ CHALLENGES OF THE MOBILE INTERNET
+ SOLUTIONS
2016 11-15 Lygature partnership meetup, Utrecht, Alain van GoolAlain van Gool
Contribution to the opening of the Joint Innovation Mile in the Beatrix building in Utrecht, home of the offices of Lygature, HealthRI, BBMRI-NL and others to follow.
Trinity park church june 22 vision budget presentationBen Meredith
The document summarizes Trinity Park Church's 2014-2015 budget and financial information from 2013-2014. It shows that while internal giving increased nearly 10% last year, external giving decreased over 60%. As a result, total income declined almost 8% in 2013-2014. The budget for 2014-2015 projects a 13.3% increase in total income and an 11.4% increase in total expenses. Key factors behind the increased budget include salary increases, higher office costs, adding new staff positions, and maintaining the church's commitment to local and international missions.
A empresa de tecnologia anunciou um novo smartphone com câmera aprimorada, maior tela e bateria de longa duração. O dispositivo também possui processador mais rápido e armazenamento expansível. O novo modelo será lançado em outubro por um preço inicial de US$799.
HIPAA is a government mandate to protect patient privacy and access to personal health information. It gives patients rights over their medical records including rights to access and correct information. HIPAA covers identifiable protected health information like names, photos, birthdates, and medical records. It requires healthcare providers to implement policies to secure this information and only provide access to those involved in treatment or payment. Non-compliance can result in civil penalties from the Office of Civil Rights or criminal penalties from the Department of Justice such as fines or imprisonment.
Este documento presenta un plan de estudios de 10 ciclos para una carrera de pregrado en Administración. Cada ciclo contiene varias asignaturas con créditos y horas de teoría, práctica y taller. Algunas asignaturas tienen prerequisitos de asignaturas anteriores. El noveno ciclo incluye un proyecto de tesis y una práctica preprofesional. El décimo y último ciclo consiste en el desarrollo de la tesis, un curso de actualización y una segunda prá
The document proposes a magazine called "Evolution of DBZ" targeted at Dragon Ball Z fans. The core audience would be any gender interested in Dragon Ball Z willing to spend £1 on the magazine. A secondary audience would include those interested in learning about anime or seeing Dragon Ball Z as an interest. The front cover would appeal to audiences with colorful images of a DBZ character and the creator portraying a fighting pose, along with a martial arts symbol relating to DBZ and the creator. The main article would provide bright, colorful information about the newest Dragon Ball franchise iteration in an engaging style. Advertisements would use big fonts to promote related anime games and cinema systems. The total proposed annual budget is £240,000,
This document is the introduction to the 2015 Global Information Technology Report, which examines how information and communication technologies (ICTs) can promote inclusive growth. Key points:
1) ICTs have the potential to transform economies and societies by improving access to services, enhancing connectivity, and creating jobs, helping address global challenges.
2) The ICT revolution is advancing in some areas due to broadband internet, democratized technologies, and accelerating innovation.
3) However, large parts of the world have not benefited from the ICT revolution. Many who could gain the most remain unconnected.
4) For ICTs to better support development, increased preparedness, infrastructure, and access are needed
state_of_app_downloads_and_monetization_2015_APACTuan Anh Nguyen
The document discusses key metrics and insights about app installs and monetization in Asia Pacific and other regions based on data from InMobi's platform. Some of the main findings are that Chinese and Indonesian users drove high app installs in 2015, with the Philippines seeing expensive iOS installs. Shopping and lifestyle apps were popular across Asia, while education and entertainment apps earned developers higher eCPMs. App install costs and earnings varied by region and operating system.
This short document provides instructions for creating a Haiku Deck presentation on SlideShare and being inspired. It encourages the reader to get started making their own Haiku Deck presentation by clicking a "GET STARTED" button at the bottom. The document contains photos but no other words.
Coding 100 session that took place a week before the Coding Camp, Berlin event (13-14 Feb 2016), to teach people to code!
See http://hackathon.cisco.com/event/codingcamp-Berlin-2016 for the Coding Camp event
The document repeatedly references #SEMrushlive "Search v Social" @logocracycopy, suggesting it is about questions or a discussion with that topic and handle on SEMrushlive. The large number of repetitions indicates a long discussion thread around comparing search engine marketing and social media marketing.
Sobornost is a foundation of ordinary people working to help children in Sub-Saharan Africa who were orphaned or at risk of malnutrition and disease. The foundation supports over 250 preschool orphans in Kenya who receive daily meals at school, 25 high school orphans in Zambia who receive food and school fees, and several orphans in India who receive yearly food support. The document asks readers to consider donating as little as $20-30 per month to feed children in these countries and help address ongoing needs such as school structures, teacher training, and expanded facilities.
Ryan Eagle founded Eagle Web Assets Inc. in 2004 after several websites hit massive success, harnessing nearly a million unique visitors a day. From the instant success of these websites, the business model was reproduced and scaled into an empire of over 450 niche websites.http://www.eaglewebassets.com/ryan-eagle.php
DEVNET-1115 Learning@Cisco: Developers + IT Professional: The Future of the I...Cisco DevNet
This document discusses the evolving skills requirements for IT professionals and the future of the IT workforce. It notes that digitization is changing business models across many industries. New digital business skills will be required related to areas like agile development, customer success management, and data analytics. Emerging jobs of the future are discussed like data scientists, cloud security specialists, and mobile application developers. There is a skills gap constraining business results. Education and careers will need to change to focus more on areas like cloud, programmability, and business outcomes. Networking roles will also evolve to focus more on areas like cloud, automation, orchestration, and programming.
2012 19-11 EC DG R&I biomarker lecture, BrusselsAlain van Gool
Invited lecture for the European Commission, Directorate General Research & Innovation, to outline developments and needs in biomarker research for biomedical applications.
This document discusses bridging research and healthcare by translating biomarkers into patient treatment. It provides background on Prof. Alain van Gool and his roles at TNO, Radboud University Nijmegen Medical Centre, and Radboud University Nijmegen. It outlines the need for biomarkers in pharmaceutical drug development and personalized healthcare to address the biomarker innovation gap and develop personal profiles for conditions like oncology and diabetes. Progress may be made through open innovation networks.
2015 10-06 Building Bridges Biomarker symposium FIMM Helsinki, Alain van GoolAlain van Gool
A unique honour and opportunity to give a 1.5 hour lecture to young biomarker scientists to introduce biomarkers and their importance in translational medicine and personalized healthcare.
2013-04-23 Top Institute Pharma Spring meeting, UtrechtAlain van Gool
Companion diagnostics use biomarkers as diagnostic tools to identify patients who will respond well to specific drug therapies. The presentation discusses the increasing use of companion diagnostics in oncology drug development and clinical trials. It provides examples of biomarkers used to identify patients with melanoma who will benefit from BRAF inhibitor drugs. While some biomarkers like BRAFV600E mutations are useful targets, tumor heterogeneity poses a challenge for companion diagnostics. The presentation calls for improving the pipeline for validating biomarkers and developing them into clinical diagnostic tests.
2014 02-24 Oxford Global biomarker congress, ManchesterAlain van Gool
This document summarizes a presentation given by Alain van Gool on biomarkers in a changing world. It discusses the shift from personalized medicine to personalized healthcare, which takes a more holistic systems view of an individual. It also notes disruptive technologies that can accelerate biomarker development and the need to translate biomarkers into useful tools. Throughout, it provides examples of challenges like tumor heterogeneity and factors beyond genetics that influence disease and response to treatment.
2013-10-10 GTC Bio Biomarker Europe Summit 2013, BerlinAlain van Gool
Using system biomarkers to combat preventable diseases
Prof. Alain van Gool discussed using a systems biology approach and biomarkers to develop personalized health management strategies. This involves continuously monitoring individuals using routine biomarkers to detect changes and "omics" data to understand the changes. Biomarker panels can provide a functional fingerprint to make personalized decisions on health and disease management interventions like nutrition, lifestyle changes, or pharmaceutical drugs. Field labs are proposed to test these concepts in real-life settings. A systems approach is needed to better understand and define diseases, leading to more mechanism-based treatments.
2020 09-07 European Center Pharmaceutical Medicine course Biomarkers, Basel, ...Alain van Gool
Tutorial lecture on biomarkers for pharmaceutical industry R&D professionals, outlining status, potential and challenges of biomarkers in pharma, clinic and society.
2015 09-14 Precision Medicine 2015, London, Alain van GoolAlain van Gool
Outline of my view hoe personalized health(care) is more than just targeted medicines, also including personal motivation and actions towards disease prevention. It also outlines 4 key factors that should be in order for optimal personalized health(care): 1. start with patients first, 2. Accelerate translation research to application, 3. Copy best practice, 4. Spread the word.
Alain van Gool presented on biomarkers in personalized healthcare. He discussed how personalized medicine is shifting to personalized healthcare with a systems view that considers multiple factors. Exponential technologies will transform healthcare in the coming years through digital medicine, self-diagnosis, artificial intelligence, and big data. However, gaps remain in translating biomarker discoveries into clinical applications and demonstrating added value. Open innovation is needed to accelerate biomarker development through multi-center validation studies.
2020 02-10 European Center Pharmaceutical Medicine course - biomarkers, Basel...Alain van Gool
This document discusses biomarkers and personalized healthcare. It begins with an overview of biomarkers in the pharmaceutical industry and how they are used from drug discovery through clinical trials. It then discusses biomarkers in academic research and healthcare, and how emerging digital biomarkers could enable personalized health monitoring. The presentation identifies some translational innovation gaps, and concludes with an outlook on how biomarkers and multi-omics approaches will continue to advance personalized diagnosis and therapies.
Lecture on biomarkers (principles, potentials, pitfalls) for 200 pharmaceutical professionals as part of the IMI Pharma Train course organised by the European Center for Pharmaceutical Medicine
2015 07-03 Nanonext NL Alain van Gool, AmsterdamAlain van Gool
The document discusses implementing personalized healthcare through measuring biomarkers. It notes that while many biomarkers have been discovered, few are validated and applied in diagnostic tests. There is also a gap in translating biomarkers into point-of-care applications. The document advocates for open innovation networks to help validate biomarkers across multiple centers and standardize clinical applications. Ultimately, the focus of personalized healthcare should be on the patient by providing individualized follow-up based on their molecular and clinical measurements.
This resume summarizes Sean Ekins' experience and qualifications. He has over 17 years of experience in drug discovery from large pharmaceutical companies to small biotechs. He is an expert in computational and in vitro tools for accelerating drug discovery and reducing compound attrition. He has held leadership roles at several companies and currently works as an independent consultant advising various organizations. He is also an active researcher and writer with over 200 publications.
2016 05-24 Kick-off The Danish Biomarker Network, Copenhagen, Alain van GoolAlain van Gool
Keynote lecture given at the kick-off of The Danish Biomarker Network in Copenhagen for a great audience of enthousiastic patients, biotech/pharma developers and ICT experts.
2013-10-02 Dutch CC symposium on Personalized Healthcare, EdeAlain van Gool
This document summarizes a presentation about companion diagnostics and personalized healthcare. It discusses how companion diagnostics can identify the right drug, dose, and timing for a patient by using biomarkers to characterize biological systems and diseases. It provides examples of companion diagnostic use in oncology and challenges in biomarker development and validation. Overall it advocates applying well-characterized therapies guided by biomarkers to better understand and treat disease in a personalized manner.
2015 12-09 Opening Radboud Translational Medicine, Nijmegen, Alain van GoolAlain van Gool
Keynote opening lecture at the grand opening of our new cyclotron facility, embedded in Radboud Translational Medicine and part of our Radboudumc Technology Centers. See http://www.radboudtranslationalmedicine.nl/nl/ for details.
This document appears to be a thesis submitted by Mr. Lahare Nikhil Ashok in partial fulfillment of the requirements for a Master of Science degree in Clinical Research. The thesis involves a randomized clinical study assessing the safety and efficacy of topical dexketoprofen gel in treating knee osteoarthritis. The study was conducted at Hardikar Hospital in Pune under the guidance of Dr. Madan Hardikar. The thesis contains sections on the introduction, aim and objectives, materials and methods, project management, statistical analysis, results and conclusions, discussion, and references.
Similar to 2013-04-17 Pharma-Nutrition Singapore (20)
2023-11-14 Biomarkers Europe 2023, Berlin, Alain van Gool.pdfAlain van Gool
Lecture at the Biomarkers Europe 2023 conference for an audience of pharma scientists and omics/data solution providers. I outlined several initiatives of potential interest and discussed development of our sensitive personalized clinical biomarker test for minimal residual disease monitoring in multiple myeloma.
2023-11-09 HealthRI Biobanking day_Amsterdam_Alain van Gool.pdfAlain van Gool
Examples of lessons learned in Omics-based biomarker studies from myself and colleagues in X-omics and EATRIS, for an audience of biobankers, researchers and diagnostic/clinical chemistry experts.
2023-04-20 EATRIS-Plus Summerschool, Lisbon, Alain van GoolAlain van Gool
Closing keynote lecture at the EATRIS-Plus summerschool on personalised medicine, outlining developments, opportunities, challenges and recommendations to do next in this exciting era of personalised medicine.
2022-11-23 DTL Future of data-driven life sciences, Utrecht, Alain van Gool.pdfAlain van Gool
A pitch on directions to improve experimental reproducibility, illustrated by examples of past experiences. I made the plee to move from 'Proudly invented here' to 'Proudly copyied from', to re-use each other's eperiences in successes and failures.
2022-10-12 The future of population health_Alain van Gool.pdfAlain van Gool
1) Exponential developments in omics technologies like genomics, proteomics, and metabolomics are driving more personalized approaches to healthcare.
2) Mass spectrometry methods have been developed to sensitively detect minimal residual disease in multiple myeloma patients from plasma samples, allowing for dynamic monitoring and earlier detection of relapse compared to traditional methods.
3) Large-scale multi-omics studies incorporating data from various sources can provide a more holistic view of health and disease at both the individual and population levels, supporting personalized prevention and treatment approaches.
2022-09-08 ECPM Digital Biomarkers and AI, Basel, Alain van Gool.pdfAlain van Gool
Lecture for 150 pharma professionals to outline the potentials and things-to-do with digital biomarkers, as part of a ECPM training on digitization and AI in drug development.
2022-04-14 EuroMedLab, Munich, Alain van GoolAlain van Gool
Keynote lecture at the EuroMedLab 2021 providing an audience of clinical chemists and laboratory medicine scientists with advancements of multi-omics applications in personalized healthcare, and challenges that we need to solve as translational scientists.
2021 12-10 Amalia Science Day, Nijmegen, Alain van GoolAlain van Gool
This document discusses the use of omics technologies like genomics, proteomics, and glycoproteomics in pediatric healthcare. Specifically, it describes a study that used glycoproteomics to analyze blood samples from children with febrile illness to distinguish between viral and bacterial infections. The analysis identified glycoprotein biomarkers that could accurately classify 70-80% of samples as viral or bacterial. Integrating multiple omics data through machine learning approaches may provide a more comprehensive understanding of diseases and lead to personalized diagnosis and treatment.
2021 06-14 EATRIS-Plus summer school, Alain van GoolAlain van Gool
Introductory lecture for the 100 participant summer school of the EATRIS-Plus project, outlining personalized medicine, biomarker and multi-omics strategies and use cases.
2019 10-14 2nd Int Congress on Precision Medicine, Munich, Alain van GoolAlain van Gool
Opening lecture at the 2nd International Congress on Precision Medicine in Munich, outlining progress in omics-based biomarkers for rare diseases, biomarker innovation gaps and multi-partner initiatives to bridge those gaps to applications. Also reviewed the highlights of our recently published Handbook of Biomarkers and Precision Medicine.
2019 09-23 COST CliniMARK summerschool, Spetses, Alain van GoolAlain van Gool
Opening lecture of the COST CliniMARK summer school 'Approaches for Biomarker Discovery and Validation'. Extensive introduction in biomarker approached used in pharmaceutical industry, academic research and clinical care, and society, combined with review of biomarker innovation gaps and outlook.
2019 06-19 Dutch association for clinical chemistry and laboratory medicine -...Alain van Gool
Sharing my views on how X-omics biomarker analyses through next gen sequencing and mass spectrometry will change the landscape of diagnostics and clinical chemistry in the near future.
Lecture describing workflows and case studies from the Translational Metabolic Laboratory @Radboudumc how to translate x-omics biomarker signatures to clinical implementation. I also highlighted new developments to join forces in the Netherlands X-omics Initiative, United for Metabolic Disease and events/book launches in the next months.
2019 03-14 Health Valley Event 2019, Nijmegen, Alain van GoolAlain van Gool
Lecture on innovations in personalized healthcare using an integrated X-omics approach towards personalized diagnostics, as part of the regional ambitious TopFit program.
2019 02-21 Oxford Global 14th Biomarker Congress, Manchester, Alain van GoolAlain van Gool
1. Professor Alain van Gool presented on using clinical x-omics to drive personalized healthcare.
2. He described case studies where combining different omic approaches like genomics, metabolomics, and glycomics led to novel disease mechanisms and therapies for rare genetic diseases.
3. Van Gool advocated for increased collaboration and standardization of omic technologies to advance precision medicine and bring clinical multi-omics to higher diagnostic and therapeutic levels.
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CHAPTER 1 SEMESTER V COMMUNICATION TECHNIQUES FOR CHILDREN.pdfSachin Sharma
Here are some key objectives of communication with children:
Build Trust and Security:
Establish a safe and supportive environment where children feel comfortable expressing themselves.
Encourage Expression:
Enable children to articulate their thoughts, feelings, and experiences.
Promote Emotional Understanding:
Help children identify and understand their own emotions and the emotions of others.
Enhance Listening Skills:
Develop children’s ability to listen attentively and respond appropriately.
Foster Positive Relationships:
Strengthen the bond between children and caregivers, peers, and other adults.
Support Learning and Development:
Aid cognitive and language development through engaging and meaningful conversations.
Teach Social Skills:
Encourage polite, respectful, and empathetic interactions with others.
Resolve Conflicts:
Provide tools and guidance for children to handle disagreements constructively.
Encourage Independence:
Support children in making decisions and solving problems on their own.
Provide Reassurance and Comfort:
Offer comfort and understanding during times of distress or uncertainty.
Reinforce Positive Behavior:
Acknowledge and encourage positive actions and behaviors.
Guide and Educate:
Offer clear instructions and explanations to help children understand expectations and learn new concepts.
By focusing on these objectives, communication with children can be both effective and nurturing, supporting their overall growth and well-being.
Hypertension and it's role of physiotherapy in it.Vishal kr Thakur
This particular slides consist of- what is hypertension,what are it's causes and it's effect on body, risk factors, symptoms,complications, diagnosis and role of physiotherapy in it.
This slide is very helpful for physiotherapy students and also for other medical and healthcare students.
Here is summary of hypertension -
Hypertension, also known as high blood pressure, is a serious medical condition that occurs when blood pressure in the body's arteries is consistently too high. Blood pressure is the force of blood pushing against the walls of blood vessels as the heart pumps it. Hypertension can increase the risk of heart disease, brain disease, kidney disease, and premature death.
Mental Health and well-being Presentation. Exploring innovative approaches and strategies for enhancing mental well-being. Discover cutting-edge research, effective strategies, and practical methods for fostering mental well-being.
End-tidal carbon dioxide (ETCO2) is the level of carbon dioxide that is released at the end of an exhaled breath. ETCO2 levels reflect the adequacy with which carbon dioxide (CO2) is carried in the blood back to the lungs and exhaled.
Non-invasive methods for ETCO2 measurement include capnometry and capnography. Capnometry provides a numerical value for ETCO2. In contrast, capnography delivers a more comprehensive measurement that is displayed in both graphical (waveform) and numerical form.
Sidestream devices can monitor both intubated and non-intubated patients, while mainstream devices are most often limited to intubated patients.
Unlocking the Secrets to Safe Patient Handling.pdfLift Ability
Furthermore, the time constraints and workload in healthcare settings can make it challenging for caregivers to prioritise safe patient handling Australia practices, leading to shortcuts and increased risks.
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As Mumbai's premier kidney transplant and donation center, L H Hiranandani Hospital Powai is not just a medical facility; it's a beacon of hope where cutting-edge science meets compassionate care, transforming lives and redefining the standards of kidney health in India.
1. Pharma-Nutrition:
a pharma perspective
Prof. Alain van Gool
Netherlands Organisation for Applied Scientific Research (TNO)
Radboud University Nijmegen Medical Centre
Radboud University Nijmegen
2nd International Pharma-Nutrition Conference
Singapore, 15-17 April 2013
2. EC DG for Research and Innovation
Alain van Gool
Brussels, 11 Sept 2012
2
Background
Molecular and cellular biology, biochemistry (BSc Eindhoven, MSc Leiden)
1991-1998 Academia - Transcription-coupled DNA repair (PhD, NL)
- DNA recombination (post-doc, UK)
1999-2011 Pharma - Organon (1999-2007) (NL)
- Schering-Plough (2007-2009) (NL, SG)
- Merck/MSD (2009-2011) (SG)
2011 – present:
Netherlands Organisation for Applied Scientific Research (TNO) (80%; Nov 2011)
– Coordinator Biomarkers for Personalized Medicine
Radboud University Nijmegen Medical Centre (20%; Dec 2011)
– Head Radboud Proteomics Center, co-chair Task Force Personalized Medicine
Radboud University Nijmegen (0%; Nov 2009)
– Visiting Professor Molecular Profiling
Biomarkers, Molecular Profiling, Translational Medicine, Personalized Medicine
www.linkedin.com E alain.vangool@tno.nl T +31-6-11783031
2ND intl Pharma-Nutrition Conference
Singapore, 17 April 2013
Alain van Gool
3. EC DG for Research and Innovation
Alain van Gool
Brussels, 11 Sept 2012
3
Outline
• Lessons learned from pharma
• Successes and failures
• Need for translational medicine
• Data-driven decision making
• Pharma 2.0
• Redefining disease
• Changed health care landscape
• Changed view on personalized health care
• Multi-parameter personal profiles
• Biomarker innovation gap
2ND intl Pharma-Nutrition Conference
Singapore, 17 April 2013
Alain van Gool
4. EC DG for Research and Innovation
Alain van Gool
Brussels, 11 Sept 2012
Successes and failures in therapeutic fields
{Kola & Landis, Nat. Rev. Drug Disc. (2004) 8: 711}
2ND intl Pharma-Nutrition Conference
Singapore, 17 April 2013
Alain van Gool
5. EC DG for Research and Innovation
Alain van Gool
Brussels, 11 Sept 2012
First human dose
to First patient
dose
First patient dose
to First pivotal
dose
First pivotal dose
to First
submission
First submission
to First
launch
Year of entry into phaseCurrent success rate
Trends in success rates by phase
CMR benchmarking study
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
2ND intl Pharma-Nutrition Conference
Singapore, 17 April 2013
Alain van Gool
6. EC DG for Research and Innovation
Alain van Gool
Brussels, 11 Sept 2012
Wanted: new toolkit
“A new product development toolkit - containing powerful
new scientific and technology methods such as animal or
computer-based predictive models, biomarkers for safety
and effectiveness and new clinical evaluation techniques -
is urgently needed to improve predictability and efficacy
along the critical path from lab concept to commercial
product.”
FDA
(White paper March 2004)
2ND intl Pharma-Nutrition Conference
Singapore, 17 April 2013
Alain van Gool
7. EC DG for Research and Innovation
Alain van Gool
Brussels, 11 Sept 2012
Limited view from the outside
Source: Gary Larson
Animal models Patient-related outcome
Source: National University Hospital Singapore
7
2ND intl Pharma-Nutrition Conference
Singapore, 17 April 2013
Alain van Gool
8. Key is to have a good view inside
High need for molecular tools that allow a look into the black box
and improve disease management: biomarkers
Drug exposure ?
Diagnosis ?
Cross-species differences ?
Patient classification ?
Prognosis ?
Target engagement ?
Modulation of mechanism ?
Off-target drug effects ?
Treatment Disease state
Mechanism ?
Other (latent) diseases ?
Disease
2ND intl Pharma-Nutrition Conference
Singapore, 17 April 2013
Alain van Gool
9. EC DG for Research and Innovation
Alain van Gool
Brussels, 11 Sept 2012
9
Biomarkers
PSA protein – blood, indicator of prostate cancer
Cholesterol – blood, risk indicator for coronary and vascular disease
MRI scan – shows abnormal tissue, like brain tumor
{Biomarkers definition working group, 2001 }
Definition: ‘a characteristic that is objectively measured and evaluated as an
indicator of normal biological processes, pathogenic processes, or
pharmacologic responses to a therapeutic intervention’
Molecular biomarkers provide a molecular impression of a biological system
(cell, animal, human)
Biomarkers can be various analytes:
2ND intl Pharma-Nutrition Conference
Singapore, 17 April 2013
Alain van Gool
10. EC DG for Research and Innovation
Alain van Gool
Brussels, 11 Sept 2012
Need for translational medicine in pharma
Issue: frequent crossing of systems barriers during drug development
Biopsies
Tissues
etc
Monkey
Pig
etc
Rabbit
Mice
Ex vivo
Rodents
DogTissues
Cell lines
Primary
cells
Diseased
human
Healthy
human
RatCellsHTS
(solution)
assays
Cell lines
Target
discovery
Lead
discovery
Lead
optimization
Pre
clinical
Phase
I
Phase
II(1)
Phase
III
Registration Launch Market
Research Development Marketing
High attrition from Research to Development (90%)
High need for translational models and tools (= biomarkers) to determine
drug exposure, efficacy and safety !!
2ND intl Pharma-Nutrition Conference
Singapore, 17 April 2013
Alain van Gool
11. 11
Translational medicine in pharma
2ND intl Pharma-Nutrition Conference
Singapore, 17 April 2013
Alain van Gool
12. • Translational medicine
− Exposure
− Mechanism
− Efficacy
− Safety
• Personalized medicine
− Diagnosis
− Prognosis
− Response
• Tools for data-driven decision making
− Biologically relevant
− Clinically accepted
− Quantitative !
− Different analytes/types
− Fit-for-purpose application
12
Biomarkers in pharmaceutical drug development
{van Gool et al, Drug Disc Today 2010}
Pharma leads way,
Nutrition and cosmetics copy
best practices,
Pharma-Nutrition: next big thing?
2ND intl Pharma-Nutrition Conference
Singapore, 17 April 2013
Alain van Gool
13. Biomarker-based translational medicine
Does the compound get to the site of action?
Does the compound cause its intended pharmacological/
functional effects?
Does the compound have beneficial effects on disease or clinical
pathophysiology?
What is the therapeutic window (how safe is the drug)?
How do sources of variability in drug response in target population
affect efficacy and safety?
Lead
Optimization
Exploratory
Development PoC
Lead
Discovery
Target
Discovery
Exposure ?
Mechanism ?
Efficacy ?
Safety ?
Responders ?
Start in Lead Discovery, complete in clinical Proof of Concept (1 strategy)
{van Gool et al, Drug Disc Today 2010}
{Kumar, van Gool, in press 2013}
13
2ND intl Pharma-Nutrition Conference
Singapore, 17 April 2013
Alain van Gool
14. EC DG for Research and Innovation
Alain van Gool
Brussels, 11 Sept 2012
Biomarker-based translational medicine strategy plans
Questions Biomarkers
& tools
Studies
& links
Comments Answers
Exposure
Mechanism
Pharmacological
efficacy
Disease
efficacy
Safety
Patient
stratification
Other
2ND intl Pharma-Nutrition Conference
Singapore, 17 April 2013
Alain van Gool
15. EC DG for Research and Innovation
Alain van Gool
Brussels, 11 Sept 2012
Biomarker-based decision making
During testing of drug in preclinical and clinical disease models:
Target engagement? Effect on disease?
yes yes !
no no
• No need to test current
drug in large clinical trial
• Need to identify a more
potent drug
• Concept may still be
correct
• Concept was not
correct
• Abandon approach
• Proof-of-Concept
• Proceed to full
clinical
development
“Stop early, stop cheap”
2ND intl Pharma-Nutrition Conference
Singapore, 17 April 2013
Alain van Gool
16. 16
Biomarker-based system biology
Saco de Visser
Adam Cohen
Scrip magazine 2003
2ND intl Pharma-Nutrition Conference
Singapore, 17 April 2013
Alain van Gool
17. EC DG for Research and Innovation
Alain van Gool
Brussels, 11 Sept 2012
17
Outline
• Lessons learned from pharma
• Successes and failures
• Need for translational medicine
• Data-driven decision making
• Pharma 2.0
• Redefining disease
• Changed health care landscape
• Changed view on personalized health care
• Multi-parameter personal profiles
• Biomarker innovation gap
2ND intl Pharma-Nutrition Conference
Singapore, 17 April 2013
Alain van Gool
18. Change in disease characterisation
• Multifactorial causes of chronic diseases are not well understood
• Risk factors include both molecular as lifestyle/environmental factors
• Treatment is often symptom-based, not mechanism-based
• System approach in diagnosis and treatment needed (systems medicine)
• Joined effort in EU to improve disease definitions and define best potential
therapies
• Translate to personalized / stratified medicine
18
{Nature Reviews Drug Discovery 2011, 10: 641}
2ND intl Pharma-Nutrition Conference
Singapore, 17 April 2013
Alain van Gool
19. EC DG for Research and Innovation
Alain van Gool
Brussels, 11 Sept 2012
19
Change in healthcare landscapes
• Health care is changing from paternal medical practice to participatory patient
• Patients involvement and ownership is growing (eg patientslikeme)
• Health care reimbursment change from production to quality (+10 years)
• Alternative ways of funding application-driven research emerge
• Crowd sourcing, stocks by end users
• Fast small grants by industry (e.g. Bayer’s grants4targets)
2ND intl Pharma-Nutrition Conference
Singapore, 17 April 2013
Alain van Gool
20. Changed view on personalized health care
20
HomeostasisAllostasisDisease
Time
Personalized health
Personalized medicine
“Health management”
Focus on resilience
“Disease management”
Focus on symptom(s)
Medical
treatment
or
Disease
Health
Non-health
21. 21
Changed view on target biology:
Working in complex human biological systems
requires a systems biology approach
Way forward:
1. Focus on key processes
2. Measure key node biomarkers
3. Convert to a functional fingerprint assay panel
4. Make actionable personalized decision on health /
disease management
5. Test added value in real life through field labs
21
22. Personal profiles
Source: Barabási 2007 NEJM 357; 4}
• People are different
• Different networks influences
• Different risk factors
22
2ND intl Pharma-Nutrition Conference
Singapore, 17 April 2013
Alain van Gool
23. RISK FACTORS
Multiparameter personal profiles
BIOMARKERS
Statistics
Selection
Ranking
INTERVENTIONS
2ND intl Pharma-Nutrition Conference
Singapore, 17 April 2013
Alain van Gool
DNA
mDNA
RNA ProteinMetabolites
Imaging
Enzymatic activity
Biochemical process
Attitude in life Social network
Stress work / private
NutritionEnvironmentPERSON-BASED
DATA
MOLECULAR LIFESTYLE / ENVIRONMENT
miRNA
24. TNO’s Systems Biology and Biomarker Tool Box
Translational preclinical models
Pharma and nutrition industry, academia (1:1, consortia)
Combine phenotypic read-outs with analytical platforms
Human studies, microdosing
Network biology + modelling
Lipidome (78 lipids)
Metabolome (198 metabolites)
Proteome (~ 4.000 proteins)
Transcriptome (~ 30.000 transcripts)
Clinical chemistry (~30 parameters)
Person-based metadata
Part in-house, part through a wide external network
Applied biomarker expertise
Discovery, statistics, validation, development, implementation
A wide network with biomarker academia and industry
Knowledge databases
Metabolic Syndrome
• Atherosclerosis
• Diabetes
• Obesity
• Vascular inflammation
• NASH, fibrosis
24
2ND intl Pharma-Nutrition Conference
Singapore, 17 April 2013
Alain van Gool
25. N-of-1 health monitoring through system biology
{Chen et al, Cell 2012, 148: 1293}
Concept:
• Continuous monitoring
• Routine biomarkers to alert
• Omics to explain
• Early intervention
2ND intl Pharma-Nutrition Conference
Singapore, 17 April 2013
Alain van Gool
26. The innovation gap in biomarker development
26
• Disconnected pipeline from biomarker discovery to application.
• Gap 1: Strong focus on discovery of new biomarkers, few biomarkers progress beyond
initial publication to multi-center clinical validation.
• Gap 2: Insufficient demonstrated added value of new clinical biomarker and limited
development of a commercially viable diagnostic biomarker test.
Discovery Clinical validation/
confirmation
Diagnostic
test
Number of
biomarkers
Gap 1
Gap 2
2ND intl Pharma-Nutrition Conference
Singapore, 17 April 2013
Alain van Gool
27. 27
Emerging
Discovery Clinical validation/
confirmation
Diagnostic
application
Number of
biomarkers
Experimental
Discovery
Assay kit
development
Assay
development
Early Late
Eg prostate cancer
May 2011: 2,231 biomarkers
Nov 2012: 6,562 biomarkers
{Source: Thomson Reuters Biomarkers Module}
– Not wise to discover yet an other biomarker
– Focus on selecting the best biomarker (panels) among those already
found (scientific and patent literature, databases, etc)
– Develop those biomarkers tot clinically applicable tests
– Open Innovation Network
Many discovered biomarkers already !
2ND intl Pharma-Nutrition Conference
Singapore, 17 April 2013
Alain van Gool
28. Way forward: Open Innovation Network
28
Shared R&D in biomarkers:
1. Assay development of (diagnostic) biomarkers
Share resources and time to develop a robust quantitative assay
2. Clinical biomarker quantification/validation/confirmation
Share resources and time by joined multi-center biomarker studies
(Model TNO’s Holst Center)
2ND intl Pharma-Nutrition Conference
Singapore, 17 April 2013
Alain van Gool
29. Biomarker stakeholders in open innovation network
29
2ND intl Pharma-Nutrition Conference
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Alain van Gool
30. European Biomarker Consortium
• Open Innovation Network
• Joined effort key partners
2013:
- Form consortium (+ EFPIA/IMI)
- Plan development of disease-
related mechanistic biomarkers
- Run projects for showcases
- Expand with projects on shared
biomarker interests
2014:
- Additional funding
- Expand with projects
- Expand to USA, Canada, (Asia?)
30
2ND intl Pharma-Nutrition Conference
Singapore, 17 April 2013
Alain van Gool
31. Personal profiles
Oncology CVD, neuro, immune Diabetes
31
Risk factor pattern is different per disease phenotype
2ND intl Pharma-Nutrition Conference
Singapore, 17 April 2013
Alain van Gool
32. Personalized medicine in Oncology
32
• Companion Diagnostics (CDx): right drug, right patient, right dose, right time
• Of 40.000 currently ongoing clinical trials, 18.000 are in oncology of which
9.000 are targeted
• Strongly driven by molecular biomarkers
• Currently 113 drug labels contain biomarker data (Cyp450, targeted) of which
32 in oncology
• CDx testing required for 16 drugs in 2012, up from 4 in 2010
2ND intl Pharma-Nutrition Conference
Singapore, 17 April 2013
Alain van Gool
Pharmacogenomic
biomarkers in
drug labels
Source FDA
Kumar and van Gool, 2013
33. Mutation-driven rational drug discovery in Oncology
V600D/E
Kinase domain
{Roberts and Der, 2007}
B-RAFV600D/E mutation: constitutively active kinase, oncogenic addiction
Overactivate ERK pathway drives cell proliferation
RAF inhibitors block growth of tumor xenografts with B-RAFV600D/E mutation
Prevalence of B-RAFV600D/E
Melanoma (60%), colon (15%), ovarian (30%), thyroid (30%) cancer
Develop B-RAF inhibitors with patient stratification opportunity
33
2ND intl Pharma-Nutrition Conference
Singapore, 17 April 2013
Alain van Gool
34. 34
Clinical efficacy of Vemurafenib (PLX-4032, Zelboraf)
Key biomarkers:
Stratification: BRAFV600E mutation
Mechanism: P-ERK
Cyclin-D1
Efficacy: Ki-67
18FDG-PET, CT
Clinical endpoint: progression-free survival (%)
{Source: Flaherty et al, NEJM 2010}{Source: Chapman et al, NEJM 2011}
34
2ND intl Pharma-Nutrition Conference
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Alain van Gool
35. 35
Clinical effects of Vemurafenib
{Wagle et al, 2011, J Clin Oncol 29:3085}
Before Rx Vemurafenib, 15 weeks Vemurafenib, 23 weeks
• Strong initial effects vemurafenib
• Drug resistancy
• Reccurence of tumors
35
2ND intl Pharma-Nutrition Conference
Singapore, 17 April 2013
Alain van Gool
36. EC DG for Research and Innovation
Alain van Gool
Brussels, 11 Sept 2012
36
• BRAFV600D/E is considered the
driving mutation
• However, varying levels of
BRAFV600D/E mutation found in
regions of a primary melanoma
• Escape mechanisms of tumors:
• Molecular heterogeneity in
diseased tissue
• Biomarker levels will vary as
well
• Similar situation within body
fluids (e.g. gradients)
• Challenge for companion
diagnostics
{Source: Yancovitz, PLoS One 2012}
Tumor tissue heterogeneity
2ND intl Pharma-Nutrition Conference
Singapore, 17 April 2013
Alain van Gool
37. Personal profiles
Oncology CVD, neuro, immune Diabetes
37
Risk factor pattern is different per disease phenotype
2ND intl Pharma-Nutrition Conference
Singapore, 17 April 2013
Alain van Gool
38. EC DG for Research and Innovation
Alain van Gool
Brussels, 11 Sept 2012
• Obesity
• Diabetes type 2
HEALTH DISEASE COMPLICATIONS
• Atherosclerosis
• Nephropathy fibrosis
• Osteoarthritis
• Stroke
• etc
Metabolic syndrome
metabolic disturbance local inflammation
Not a single cause but complex multifactorial diseases
Disturbed equilibrium between multiple pathways and key components
Inhibition/stimulation of a selected step shifts equilibrium to a potential bottle neck elsewhere
A system biology approach is needed
For discovery research, diagnosis and treatment
Most effective therapy is ‘eat better, move more’ (lifestyle change)
Nutriceuticals / Lifestyle
Food
Pharma
38
2ND intl Pharma-Nutrition Conference
Singapore, 17 April 2013
Alain van Gool
39. Overall scheme of metabolic disorder related processes
Myocardial
infactions
Heart
failure
Cardiac
dysfunction
dyslipidemia
Metabolically
healthy
High cholesterol High glucose Hypertension
Brain
disorders
NephropathyAtherosclerosis StrokeRetinopathy
Risk factors of the ‘metabolic syndrome’
Pathologies resulting from the ‘metabolic syndrome’
Visceral
adiposity
LDL elevated
Glucose toxicity
Fatty liver
gut
inflammation
endothelial
inflammation
systemic
Insulin resistance
systemic
inflammation
Hepatic IR
Adipose IR
Muscle metabolic
inflexibility
adipose
inflammation
Microvascular
damage
Myocardial
infactions
Heart
failure
Cardiac
dysfunction
Brain
disorders
Nephropathy
Atherosclerosis
β-cell failure
Reversible process
β-cell Pathology
High cholesterol
High glucose
gluc Risk factor
Hypertension
dyslipidemia
ectopic
lipid overload
Ìrreversible process
Hepatic
inflammation
Stroke
IBD
fibrosis
Retinopathy
Metabolically
healthy
{Nakatsuji, Metabolism 2009}
40. Many drugs interfere with these processes in “health care”
Visceral
adiposity
LDL elevated
Glucose toxicity
Fatty liver
gut
inflammation
endothelial
inflammation
systemic
Insulin resistance
systemic
inflammation
Vioxx
Salicylate
Atorvastatin
Fenofibrate
Metformin
Glibenclamide
LXR agonist
Rosiglitazone
Pioglitazone
Sitagliptin
Hepatic IR
Adipose IR
Muscle metabolic
inflexibility
adipose
inflammation
Microvascular
damage
Myocardial
infactions
Heart
failure
Cardiac
dysfunction
Brain
disorders
Nephropathy
Atherosclerosis
β-cell failure
Reversible process
β-cell Pathology
High cholesterol
High glucose
gluc Risk factor
Hypertension
dyslipidemia
ectopic
lipid overload
Ìrreversible process
Hepatic
inflammation
Stroke
IBD
fibrosis
Retinopathy
Metabolically
healthy
Physical inactivityCaloric excess
reversibleirreversible
41. Many dietary ingredients optimize these processes
Visceral
adiposity
LDL elevated
Glucose toxicity
Fatty liver
gut
inflammation
endothelial
inflammation
systemic
Insulin resistance
systemic
inflammation
Hepatic IR
Adipose IR
Muscle metabolic
inflexibility
adipose
inflammation
Microvascular
damage
Myocardial
infactions
Heart
failure
Cardiac
dysfunction
Brain
disorders
Nephropathy
Atherosclerosis
β-cell failure
Reversible process
β-cell Pathology
High cholesterol
High glucose
gluc Risk factor
Hypertension
dyslipidemia
ectopic
lipid overload
Ìrreversible process
Hepatic
inflammation
Stroke
IBD
fibrosis
Retinopathy
Metabolically
healthy
Carnitine, Choline, …
Caloric restriction
Soy …
Low glycemic index
Physical activity
Stannols, fibre
reversibleirreversible
Omega 3/6 FA
Quercetin, Se, Zn, …
procyanidins
epicathechins
caretonoids
anthocyanins
polyphenols
42. Each organ has its own
characteristics in
maintaining/loosing
flexibility and this
determines the
health to diabetes
transition.
{Nolan, Lancet 2011}
A sure need for system biology
High need to study the
effect of drugs/nutrition
on each of these organs
and their interaction
within the whole system
of each person.
43. Important processes in
T2D
Diagnosis Potential interventions
Dietary/LS Pharma
1.Pancreatic β-cell function
(impaired insulin secretion)
*OGTT: I/∆G and DI(0)
*PYY, Arg, His, Phe, Val, Leu
Lifestyle; β-cell
protective nutrients
(MUFA/isoflavonoids);
β -cell protective
medication (TZDs,
GLP-1 analogs,
DPP4-inhibitors)
2.Muscle insulin resistance
(decreased glucose uptake)
*OGTT: Muscle insulin resistance index,
Insulin secretion/insulin resistance index
*Val, Ile, Leu, Gamma-glutamylderivates,
Tyr, Phe, Met
PUFA/SFA balance;
Physical activity;
Weight loss;
TZDs (e.g.PPARγ)
3.Hepatic insulin resistance
(decreased glucose uptake and
increased hepatic glucose
production-HGP)
*Hepatic insulin resistance index *OGTT:
Hepatic insulin sensitivity index
*ALAT, ASAT, bilirubine, GGT, ALP, ck-18
fragments, lactate, α-hydroxybutyrate,
β-hydroxybutyrate
Decrease SFA and n-
6 PUFA, and increase
n-3 PUFA;
Weight loss;
Metformin;
TZDs;
Exenatide (GLP-1
analog);
DPP4 inhibitors
4. Adipocyte insulin resistance
and lipotoxicity
*basal adipocyte insulin resistance index
*FFA platform, glycerol
α-lipoic acid;
PUFA/SFA balance;
Omega 3 fatty acids;
Chitosan/plantsterols;
TZDs; Acipimox
5. GI tract (incretin
deficiency/resistance)
*ivGTT vs OGTT
*GLP-1, GIP, glucagon, galzuren
MUFA; Dietary fibre
(pasta/rye bread);
Exenatide
6. Pancreatic α-cell
(hyperglucagonemia)
*fasting plasma glucagon ? Glucagon receptor
antagonists;
Exenatide;
DPP4 inhibitors
7A.Chronic low-grade
inflammation in pancreas,
muscle, liver, adipose tissue,
hypothalamus
7B. Vascular inflammation
*CRP, total leucocytes
* V-CAM, I-CAM, Oxylipids, cytokines
Fish oil/n-3 fatty
acids; Vit. C/Vit.
E/Carotenoids;
Salicylates; TNF-α
inhibitors and others
44. EC DG for Research and Innovation
Alain van Gool
Brussels, 11 Sept 2012
Comparing nutritional versus drug intervention
Age-matched “healthy” control group
t=16 w
(sampling)
t=9 wt=0
Induction of Diabetes intervention period
High-fat (HF) diet
High-fat diet “diseased” control group
Nutrition/Life style switch
HF + Drug 1
HF + Drug 2
HF + Drug 3
….HF + Drug 10
44
2ND intl Pharma-Nutrition Conference
Singapore, 17 April 2013
Alain van Gool
45. 45
Effects on total adipose tissue weight
Most effective therapy is ‘eat better, move more’ (lifestyle change)
But people respond differently to interventions (depending on their personal profile)
2ND intl Pharma-Nutrition Conference
Singapore, 17 April 2013
Alain van Gool
46. EC DG for Research and Innovation
Alain van Gool
Brussels, 11 Sept 2012
Field labs: test health care concepts in real life
• Build field lab with pre-diabetic patients, physicians, dietitians, insurers, etc
• Measure individual ‘risk’ parameters for metabolic syndrome +/- challenge
• phenotypes, clinical chemistry, specific Omics, etc
• Convert data into a personal profile + personalized health advice
• life style +/- nutrition +/- pharmaceutical drugs
• Test personalized health concept in field lab following P4 medicine principle
46
2ND intl Pharma-Nutrition Conference
Singapore, 17 April 2013
Alain van Gool
47. 2ND intl Pharma-Nutrition Conference
Singapore, 17 April 2013
Alain van Gool
P4 field lab
Query customer
Personalized advice
Coaching
Monitoring
Feedback
Analysis
Challenge tests
Personal Omics
Lab-on-chip
Measure preferences
Sense making
Smart querying
Smart algorithms
Knowledge integration
Interactive apps
eHealth
Avatar
Serious gaming
Wearable devices
Activity reporting
Emotion reporting
Intelligent communication
Personal Health Dossier
Data integration
Virtual populations
Dynamic consent
Assess health status
NL Topsector Life Sciences & Health+ links to NL, EU and USA consortia
(nutrition, pharma, P4 medicine,
biomarkers, ICT, systems biology)
Human
interaction
Technological
support
48. Personal profiles
Oncology CVD, neuro, immune Diabetes
48
Risk factor pattern is different per disease phenotype
2ND intl Pharma-Nutrition Conference
Singapore, 17 April 2013
Alain van Gool
49. EC DG for Research and Innovation
Alain van Gool
Brussels, 11 Sept 2012
Redefining disease
{Nature Reviews Drug Discovery 2011, 10: 641}
49
2ND intl Pharma-Nutrition Conference
Singapore, 17 April 2013
Alain van Gool
50. EC DG for Research and Innovation
Alain van Gool
Brussels, 11 Sept 2012
Human Diseasomes
From Barabási 2007 NEJM 357:4
Redefining disease
50
2ND intl Pharma-Nutrition Conference
Singapore, 17 April 2013
Alain van Gool
51. EC DG for Research and Innovation
Alain van Gool
Brussels, 11 Sept 2012
Redefining disease
Proposed procedure
for network-based
drug discovery for
personalized therapy
Source: Schadt et al, 2009, Nature, 8:268}
51
2ND intl Pharma-Nutrition Conference
Singapore, 17 April 2013
Alain van Gool
52. EC DG for Research and Innovation
Alain van Gool
Brussels, 11 Sept 2012
Redefining disease: Medicine 3.0
Concept:
• Identify and quantify common
mechanisms of chronic diseases
• Identify new targets for intervention
• Target causes of disease rather than
symptoms
NL: Proposal submitted (10 yrs, 30MEur)
EU: Align with IMI and Horizon2020
52
2ND intl Pharma-Nutrition Conference
Singapore, 17 April 2013
Alain van Gool
54. EC DG for Research and Innovation
Alain van Gool
Brussels, 11 Sept 2012
van Wietmarschen H et al. JCR. 2009;15(7):330-337.
RA Cold RA Heat Control
Treatment 1 Treatment 2
64
differentially
expressed
genes
Subtyping of Rheumatoid Arthritis based on Heat & Cold patterns
Hierarchical
clustering
2ND intl Pharma-Nutrition Conference
Singapore, 17 April 2013
Alain van Gool
55. EC DG for Research and Innovation
Alain van Gool
Brussels, 11 Sept 2012
DXXK consists of the total saponin extract of the rhizomes of Dioscorea nipponica Makino,
mainly composed of steroidal saponins
Patent protected China and EU by DIAO
> 100 scientific studies (16.000 patients)
Used by >100 Million people
Production process DIAO is approved for EU cGMP in 2009
Approved for NL market 14 March 2012
Bridging Tradional Chinese Medicine to the West
Registration as tHMP in NL by
TNO/SU BioMedicine in collaboration with DIAO
NATURE NEWS BLOG, April 19, 2012
Chinese herbal medicine breaks into EU
Market
2ND intl Pharma-Nutrition Conference
Singapore, 17 April 2013
Alain van Gool
58. EC DG for Research and Innovation
Alain van Gool
Brussels, 11 Sept 2012
Thank you
58
Jan van der Greef
Ben van Ommen
Peter van Dijken
Robert Kleemann
Hans Princen
Tom Rullmann
and many others at
Bas Kremer
Marijana Radonjic
Suzan Wopereis
Lars Verschuren
Rob Stierum
Nard Clabbers
Wim van Hartingsveldt
Robert Ostendorf
Simon Folkertsma
Steven Erpelinck
Gerrit Beumer
alain.vangool@tno.nl
2ND intl Pharma-Nutrition Conference
Singapore, 17 April 2013
Alain van Gool