Plenary 3 Ministerial Address


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  • Chronic diseases are the leading cause of mortality in the world, accounting for 36 million deaths in 2008 – 63% of the total global deaths, and more than all other diseases combined. Over a quarter of all patients who die from chronic diseases are under the age of 60. The leading causes of deaths are cardiovascular disease, cancer, chronic respiratory disease and diabetes. The World Health Organisation has warned that the number of deaths from these diseases will increase by 15% between 2010 and 2020 (to 44 million deaths,reaching 52 million by 2030] and by over 20% in some parts of the world such as Africa, South East Asia and the Middle East.Chronic diseases can be attributed to a combination of genetic, environmental and lifestyle factors. Many chronic diseases are caused by preventable and modifiable factors, such as smoking, insufficient physical activity, excess alcohol use, and unhealthy diet. An ageing population and economic influence on lifestyle choices in developing countries has resulted in increased prevalence of chronic diseases.Up to three quarters of people over 75 years of age currently suffer from a chronic disease It is estimated that the incidence of chronic disease in the over 65s will double by 2030 WHO data show that 75% of the population has one chronic disease and 50% have two or more conditions.
  • for linkage of data from diabetes registers collected in each Health Board in Scotland stored on a central server to other health records including mortality linked Scottish Morbidity Records held by ISDACaDMe = acute episodes, cancer, deaths, mental health
  • Benchmarks: public interest, safe people, safe systems, safe environment, relative risks.Privacy risk assessment: based on criteria such as disclosiveness, sensitivity etc.
  • Plenary 3 Ministerial Address

    1. 1. Options and Opportunities for Health Science Innovation in Scotland DRIVING QUALITY THROUGH INNOVATION Andrew Morris Chief Scientist Scottish Government Health Department NHS Conference, 22nd June, 2012
    2. 2. The next 30 minutes Current challenges Gearing an entire country for quality health care and research Information science as the catalyst for change The role of academic health science networks Case studies
    3. 3. The birth of the NHS “…quite the most ambitious adventure in the care of national health that any countryVisit of Mark WalportAneurin Bevan, Lancet, July 3 1948 rd and James Rothman, 15th November, 2007 has seen”
    4. 4. Visit of Mark Walport and James Rothman, 15th November, 2007
    5. 5. Framingham  1948  All 5,200 town residents  Aged 30-62 years  Regular “health checks”  Three generations of participants  Iconic epidemiological studyVisit of Mark Walport and James Rothman, 15th November, 2007
    6. 6. What did it tell us?  “Risk factors” – High blood pressure – Smoking – Cholesterol – Diabetes  Links to heart attacks and stroke “Has resulted in an average of four extra years of life” C Lenfant, Shattuck Lecture, 2003Visit of Mark Walport and James Rothman, 15th November, 2007
    7. 7. “The Town That Changed Americas Heart”Visit of Mark Walport and James Rothman, 15th November, 2007
    8. 8. The new horizon - The Human Genome Project •Map of the three billion letters that make up the code of life “It is rather like reaching the top of a mountain pass and seeing in front of you a fertile plain, rich with new ideas, new methods, new techniques and new concepts for understanding the complexity of human biology in health and disease” M Bobrow....and informatics is fundamental to the success of thisrevolution in science” A Morris, NHS Conference, June 2012Visit of Mark Walport and James Rothman, 15th November, 2007
    10. 10. DEATHS from CAUSED by:chronic disease in 2008:Up to three quarters of people over 75 years of age currently suffer from a chronic disease It is estimated that the incidence of chronic disease in the over 65s will double by 2030 Approximately 44% of all chronic disease deaths occur before the age of 70 WHO data show that 75% of the population has one chronic disease… ...and 50% have two or more conditions Mortality will increase by 17% in next decade and by 25% in Africa and Middle East
    11. 11. DIABETES • Affects 366 million people (6.4% of world population) • 4 million deaths attributable to diabetes annually • Number affected will increase to 552 million by 2030 • 80% of current cases occur in low and middle income countries • Largest age group affected in 2010 was 40-59 years. This will move to 60-79 year age group by 2030 • Type 2 diabetes accounts for 85-95% of all diabetes in high income countries
    13. 13. IMPACT ON HEALTHCARE SERVICES • Patients with a chronic disease use > 60% of hospital bed days • Three quarters of patients admitted as medical emergencies have an exacerbation of a chronic condition • Patients with three or more chronic conditions (15%) account for 30% of total inpatient days • A small number of patients (10%) account for 55% of total inpatient days
    14. 14. ECONOMIC IMPACT • UN summit 2011 declared chronic diseases to be a global threat to future sustainability and affordability of healthcare delivery • World Economic Forum placed chronic diseases amongst the most important and severe threats to economic growth and development • Institute of Medicine study found that chronic diseases currently costs developed countries 0.02-6.77% of GDP • World Economic Forum estimates that chronic diseases will cost world economy $47 trillion over next 20 years • Chronic disease management estimated to cost 75% of GDP by 2030
    15. 15. Population-based study 1.75M people in Scotland 42.2% one or more CDs “Management of patients with several chronic diseases is now the most important task facing health services in developed countries, which presents a fundamental challenge to the single- disease focus that pervades medicine”Lancet May 15th 2012
    17. 17. How are we responding to this challenge?
    18. 18. Our Thesis Quality Health Care and Research: From Cell to Community NHS Research Scotland Health Science Scotland World Class Translation, Excellence Patient care Trials and In Life Innovation SciencesCommunity Cell
    19. 19. Informatics to support patient care
    20. 20. Population 5MSingle health care providerStability of health structuresHigh rates of morbidity of commoncomplex diseaseCollaboration –Aberdeen, Edinburgh, Dundee, Glasgow, St Andrews Layered access Links to CHI / NHS recordsUnique patient identifier records Prescription
    21. 21. Community Health Number 07 10 64 02 5 0Date of Birth Sex Check
    22. 22. Linking Data - the key to seamless care Lab Data CHI AHPs Pharmacy GP Hospital Eye Van ScreeningInvestigations
    23. 23. A National Diabetes System for ScotlandTotal Scottish Population 5.2MPeople with diabetes : 251,004(4.6%)People with Type 1 DM : ~27,000(0.5%)All patients nationally are cared forwith a single clinical informationsystem SCI-DCSCI-DC used in all hospitalsNightly secure sharing of datafrom all 1043 primary carepractices across Scotland
    24. 24. National Data Standards and Quality Assurance
    25. 25. Team on the job!
    26. 26. Miracles• 10 patients found - according toNHS Sources - dead!• Life after Death = range 1- 4 years• Resurrection Rate = 0.092
    28. 28. SCI-DC is a fantastic clinical tool!Visit of Mark Walport and James Rothman, 15th November, 2007 24 September, 2010 th
    29. 29. Scottish Diabetes Survey 2002-2007 Recording of Key Biomedical MarkersPercentage of Patients Data recoded within the previous 15 months Source: Scottish Diabetes Survey
    30. 30. Evidence of improved clinical outcomesDiabetic Medicine 2009 Diabetes Care 2008
    31. 31. Latest Scotland wide data Kennon et al; Diabetes Care; 2012; in press
    32. 32. “If you live in Dundee and suffer fromdiabetes, you have recently been taking part in a medical revolution.”Sir Mark Walport, The Times, 30th May, 2011
    33. 33. Is this new? When you can measure what you are speaking about, and express it in numbers, you know something about it; but when you cannot express it in numbers, your knowledge is of a meagre and unsatisfactory kind; Institute of Engineers, 3rd May 1883 Lord Kelvin, 1824-1907“If you cannot measure it, you cannot improve it”
    34. 34. Can changes toorganisation and delivery of care improve quality of care and outcomes?
    35. 35. Chronic care management in nineleading US physician organisations Puget Sound Mayo Clinic Marshfield Clinic Park Nicollet Clinic Henry Ford MC Cleveland ClinicKaise Permanante Inter Mountain Health Lovelace Clinic BMJ 2002; 325; 958-61
    36. 36. Factors determining success Barriers Facilitators Lack of financial and staff  ORGANISATIONAL CULTURE resources SUPPORTS QUALITY IMPROVEMENT LACK OF CLINICAL  ELECTRONIC MEDICAL INFORMATION SYSTEM RECORD Doctors are busy  Supportive managerial and No financial incentive for medical leadership quality care  Support from external Doctors resist change organisations (Health Plans)  Organisation‟s strategic plan
    37. 37. Levels of Information Assurance ASSURANCE Validated Data for 6 domains: Access, Efficiency, Infection & Prevention, Quality & Board Patient Experience, Patient Safety and Data QualityData and Measurement for Performance PERFORMANCE ET Validated and un-validated data across 6 domains: EMT Clinical Excellence, Finance & Activity, Valuing Staff, Capacity & Activity Planning, Patient Experience Directorate / CHP and Patient Safety Improvement IMPROVEMENT Ward / Team Level Un-validated data provided in real time through Unified Patient Tracking, Clinical Portal and operational Patient / Practitioner Level dashboard with metrics covering Patient Flow, Inpatient Activity, Out Patients, Waiting Times, Patient Safety, Infection Control, Clinical Outcomes Patient to Board“focusing on information and data to provide assurance on improvement and quality to deliver better, safer care”.
    38. 38. July 2011 compliance with the 62 day cancer target Number Number % Site within treated Compliance 95% Target Target Strategic Dashboard Report Breast 25 25 100% Cancer Performance Colorectal 14 11 78.6% Compliance 94.6% Head & Neck 1 0 0% Lung 16 16 100% Cancer 62 days capability Gynaecology - Ovarian 4 4 100% UGI - Hepatopancreastobiliary 2 2 100% 62-day Standard % Compliance 95% HEAT Target UGI - Oesophagogastric 3 3 100% 100 Urology - Bladder 1 1 100%Compliance Rate 80 Urology – Prostate 8 8 100% 95% HEAT Target 60 Urology – Other 4 4 0% 40 Gynaecology – Cervical 0 0 - 20 0 TOTAL 75 71 94.6% Nov Oct July Dec Jan Aug 11 Sept 11 11 12 11 11 11 Run Chart showing Commentary July 2011 – The figures for July indicate that performance for the 62 day (patients referred urgently with suspected January 2012 cancer target was 94.7% overall. Performance across all sites was below the 95% HEAT target.
    39. 39. Data Information for Improvement Contains extensive datasets including appropriate dates such as referral, appointment, wait ing list, waiting times between stages.Operational real-timedashboardsExploiting existing informationsources – record information once, use many times – deliver information as near to real time as possibleFocusing on intuitive, userfriendly presentation.
    40. 40. The Innovation Pathway World Class Translation Excellence Patient care Trials and In Life Innovation SciencesCommunity Cell
    41. 41. Health Science Scotland• “NHS Scotland‟s new platform to support research for patient benefit and foster related economic development” • Initially four Health Boards, four University, SE Partnership Launched June 2009; Health Minister and Finance Minister
    42. 42. The best clinical research and innovation laboratory in the world NHS Boards Universities
    43. 43. Key ingredients for change • a strong science infrastructure with vibrant PhD and post doctorate communities• Academic Health Science Networks with a tripartite mission and significant infrastructure investment • a commitment to linking information from medical and non- medical sources using electronic patient records to support better treatment, safety and research • a new pathway for the regulation and governance of health research • collaborative arrangements with the biotechnology pharmaceutical and medical devices industries • positioning Scotland as a single research site
    44. 44. Health Science Scotland Health Science Scotland Executive structure Health Science Scotland Oversight Board Chair - Chief Medical Officer Scottish Government, CEO Health Boards, Vice Chancellors Health Science Scotland Executive Convenor – Chief Scientist Chief Scientist Office, Medical Deans, NHS R&D Directors Health Science Scotland Central Portal Programme management, CommunicationsRecognising the need for critical mass in academic excellence and healthcare systems to compete as a global destination for medical research the Collaboration was formed in 2005.
    45. 45. Key Delivery Units NHS Research Scotland Clinical Research FacilitiesTissue acquisition „Safe Havens‟ service Health informatics Biorepositories research Project management Research imaging Quality & Facilitation platform
    46. 46. NRS Infrastructure investment Core research dedicated staff in NHS 188 WTE staff WTE86 WTE staff CRF nurses/admin 63 Biorepository 29 Research Imaging 26 Informatics Research 16 Quality/ Governance 22 Clinical trials support 332009/10 2010/11 2011/12 £4.5m £10m Central functions 6.5 WTE manager + admin staff NRS PCC, databases, contracts, research passport
    47. 47. Clinical Research Centres• State of the art clinical research facilities• Part of a managed network across Scotland• All have generic research nurse teams• All have specialised staff with specific clinicaland technical skills
    48. 48. Biorepository networkStrategic national collections• Rheumatoid arthritis• Renal cancer• Type 1 diabetes• Generation Scotland/ SHHSNational/ local planned collections NRS NE• Generic consent• Strategy driven NRS E• Future focusBespoke collections NRS W NRS SE• Specific consent• Project based Infrastructure development • Inventory management system• Investigator „owned‟ • Patient record linkage • Enhanced storage capacityPathology archive • Facilitated rapid access ~200,000 consented for genomic studies
    49. 49. Informatics Information from cradle to grave...• Mothers ante-natal records• Maternity• Neonatal record• Register birth - NHS number• Register with GP - CHI• GP systems• Dental Appointments• Outpatients• A&E attendance• General hospital admission (ICD10/OPCS4)• Prescribing – community pharmacies• Cancer registration• Cancer treatment• Community care• Death
    50. 50. Health Informatics Centres NHS Data stores SAFE HAVEN Storage Area Network Prescribing Mortality (GROS)Secure storage Hospital episodespower protection (SMR: ISD)camera surveillance Identification (CHI) Integrated datasets laboratory phenotype (SCI store) Imaging phenotype (PACS) Dumb terminals NHS staff Primary Care? Accredited academic staff
    51. 51. 320-MDCT 3T MRI 128-mCT/PET Cyclotron SINAPSE “calibrain” The scanner harmonisation problem • Each scanner presents a unique bias • Harmonising pre-processing approach
    52. 52. Reducing Regulatory Burden Single sign off across ScotlandNRS Permissions CC- Approvals NRS- Costing CC- Contracting NRS NE- Reciprocity with NIHR CSPRegional working – 4 hubs NRS E- ethics- R&D management NRS W NRS SETargets- Ethics approval in 30 days (Scottish average)- R&D 95% approved in 30daysUniversities umbrella agreement of single contracting
    53. 53. NRS Permissions Co-ordinating Centre Performance Table 1 Time (working days) to approval for multi-site studies Time to permission for all Scottish sites Non-commercial CommercialNotes :Time to permission is the number of working days elapsed between the receipt of a „full document set‟ by the PermissionsCentre and management approval by all Scottish sites. It includes the time taken for generic review of principal governanceissues by the lead review site (once for Scotland) and for local review of resource availability.
    54. 54. Case Studies Trials Evaluation of policy Genetics National programmes Exporting the Model
    55. 55. Informatics Driving Efficiency in Clinical Trials• Scottish Diabetes Research Network• National collaboration for clinical trials• Research register of patients – On personal approach, 70% of patients agree to join the register. – By invitation letter from GP, 50% of patients agree to join.• Major programmes from EU (SUMMIT €24M), Innovative Medicines Initiative (DIRECT €22M), JDRF (£3,5M)•
    56. 56. Research CriteriaWelcome: Emma Riches Patient Specific Criteria Please complete the form below in order to generate a list of people with diabetes who meet the specified criteria of the study; People with Diabetes Type = Age Criteria: Biochemistry Criteria Blood Pressure: BMI: Cholesterol: Creatinine: HbA1c: The above values need to be recorded within the; Submit Reset Please Select Diabetes Type Drop down options;  Type 1  Type2  Both Type 1 & 2 Please Select Drop down for BP/ BMI/ Cholesterol/ Creatinine/ HbA1c;
    57. 57. Case Study• Phase III NCE cardiovascular outcomes trial.• target recruitment 10 patients in 18 months.• 10 patients contacted from research register, all 10 screened and randomised.• Site hit target in < 2 weeks and was global top recruiter for 3 months.
    58. 58. Number of Studies & Participants 2007 2008 2009 2010 2011 Academic 57 80 95 97 73 Commercial 26 37 44 61 58 Total(s) 83 117 139 158 131 2007 2008 2009 2010 2011No. of Participants 2655 4860 6171 6434 8830
    59. 59. Efficient trial follow upWest of Scotland Coronary Prevention Study PlaceboCHD related death or MI Log-rank p=<0.0001 Pravastatin Original trial Ford et al, N Eng J Med (2007) 357 1477-86
    60. 60. Case Studies Trials Evaluation of policy Genetics National programmes Exporting the Model
    61. 61. Non-experimental evaluation (policy)Effect of smoking legislation in Scotland Admissions fell by 17% - 67% of reduction was in non-smokers Before ban 5.2% increase per annum Fall in England 4% (no legislation); After ban 18.2% decrease per annum long term trend 3%Acute Coronary syndrome Childhood asthmaPell et al, N Eng J Med (2008) 359; 482-491 Pell et al New Engl J M 201o, 363 . pp. 1139-1145
    62. 62. Case Studies Trials Evaluation of policy Genetics National programmes Exporting the Model
    63. 63. The population modelScotland Phenotyped cohorts Genetic Epidemiology Translational Programmes Epidemiology & Trials
    64. 64. “The outstanding longitudinal tracking you have in place will add considerable information …….there is no doubt that a resource like this is desperately needed.” David Altshuler Department of Genetics, Harvard Medical School;Department of Medicine, Massachusetts General Hospital
    65. 65. GENETICS - ADDING VALUE TO RESEARCH:BIOBANKING PROGRAMMES• Generation Scotland • Scotland wide • >30,000• UK Biobank • 50,000 Scots recruited • Exemplar of informatics linkage• Colon cancer• Cardiovascular disease• Type 2 Diabetes • >20,000 • DNA distributed nationally• Type 1 Diabetes • Scotland wide • 10,000
    66. 66. The UK Type 2 Diabetes Genetics Consortium
    67. 67. Illustration of the power of genetics Studies in twins separated at birth Dizygotic Twins Monozygotic Twins Borjeson,Acta Paed.1976
    68. 68. Is it worth studying genetics of chronic diseases? Diabetes life time risk 0 Parent 10% 1 Parent 30% Brother/sister 40% Both parents 70% Identical twin 80-100 %Can molecular genetics define pathophysiology?
    69. 69. Slow progress….Glazier et al, Science, 2002
    70. 70. Until.....the march of technology!! single variant (100 SNPs; 103 genotypes) detailed study of individual genes (102 SNPs; 105+ genotypes) regional studies (104 SNPs; 108 genotypes ) genome-wide association (106 SNPs; 1010 genotypes) complete resequencing (108 SNPs / 1012 genotypes)
    71. 71. Map of diabetes susceptibility June 2012 Effect size PNDM HNF1A other MODY few if any genesLarge TNDM up here Other rare syndromes mt3243 LMNA TCF7L2 FTO PPARG CDKAL1 IGF2BP2 CDKN2A LARS2 SLC30A8 KCNJ11 ACDC CAPN10 WFS1 HHEX HNF4A Not in my LMNA INS Lifetime!Small Allele Rare Common frequency
    72. 72. Now we have some genes… Clinical medicine Genetics: Do these variants allow us to predict disease progression (eg from prediabetes) and the effect of Which are the aetiological variants lifestyle interventions?Genetic epidemiology Confirmed Cell biology How does variation hereinteract with variation at other sites? variants What are the molecular mechanisms? Pharmacogenetics Do these variants also influencecomplication risk, or response to Physiology What are the physiological correlates available treatments? Epidemiology of these variants? What is the population risk and are there important interactions with exposures?
    73. 73. WILL IT HELP PRESCRIBING?THERE IS CONSIDERABLE VARIATION IN RESPONSE TO MOST DRUGS Baseline Hba1c 8-9% 60 50 Mean reduction = 1.315 Std. Dev. = 1.05189 40 N = 290 30 Frequency 20 10 0 -3.00 -2.00 -1.00 0.00 1.00 2.00 3.00 4.00 Absolute HbA1c reduction Data from DARTS, Tayside, Scotland
    74. 74. PHARMACOGENETICS: • In use for over 50 years • We still don‟t understand how it works • 25% of patients get GI intolerance; • 5% cannot continue it • Can we use genetics to help us? • Ability to link genetics with GWAS Metformin Response Q-Q plot drug exposure and therapeutic response
    75. 75. The gene links cancer pathways, metformin pathwaysand type 2 diabetes
    76. 76. Case Studies Trials Evaluation of policy Genetics National programmes Exporting the Model
    77. 77. National Collaborations Wyeth 2006-2011 Grand Challenges 2011-2014 Preferred Site Preferred Site National Informatics Programme Scottish Stem Cell Network Generation Scotland
    78. 78. Case Studies Trials Evaluation of policy Genetics National programmes Exporting the Model
    79. 79. Internationalisation Kuwait Scotland eHealth Innovation Network“The Scottish Health SciencePackage”•Scientific Research•Education•Clinical Skills•Informatics
    80. 80. Education• PG Certificate/Diploma/MSc Diabetes Care & Education – training the multi-disciplinary health care team – 120 students enrolled• Two „Discovery Courses‟ have exposed 400 HCPs in Kuwait to latest diabetes knowledge (March & May 2011)• “OSCE” assessments and workshops for Nurse Educators, Nutritionists, Call centre team• National Clinical Skills Facility – 1st of its kind within GCC, modelled on world-class facility at University of Dundee – Provides novel and safe training environment for all HCPs in Kuwait 82
    81. 81. KHN Designs: Home page Service Improvement Find patient quickly Integrated Community Learning tools
    82. 82. Scotland as a Single Research Site Challenges for Delivery “However, access to clinical data ……is currently hampered by a fragmented legal framework, inconsistency in interpretation of the regulations, variable guidance and a lack of clarity among investigators, regulators, patients and the public”
    83. 83. It’s true in Scotland!Linkage of SCI-DC to SMR 01• R&D approval from 14 Boards – 8 page form, covering letter, CV, proposal, sponsor letter, funder letter• Ethics approval 23 page form• PAC approval 11 pages• 14 Caldicott guardian approvals – Initially difficult to identify – Took 4 months to get all replies – Multiple contacts - 5 requested further information – “end to end” 16 months
    84. 84. £3.9M 2009-2012NW HIEC October 2011
    85. 85.
    86. 86. Recommendations• Governance Infrastructure• Research Infrastructure• National Safe Haven – located in NSS• Model to be mirrored at Health Science Scotland nodes
    87. 87. Proportionate Governance Category 3: High impact full review possible further conditions Category 2: Medium impact Fast track review – possible further conditions Category 1: Low impact Stage 2 No further review: standard Stage 1 terms and conditionsBenchmarks Privacy Risk Assessment Category 0: Public domain No further conditions
    88. 88. Scotland : A World Leading Global Hub 10 “C‟s for Success” Clinical quality Collaboration Centres of Scientific Excellence Connectivity across NHS/Universities Commercial engagement - encouraged Clinical Trial Permissions/Regulation Clinical Informatics using the CHI Clinical Research Facilities Collections of tissues/DNA Clinical Research Imaging
    89. 89. The Final “C” Beware! Complacency -Competition is Fierce
    90. 90. Commissioning Development ProgrammeAcademic Health ScienceNetworks May 2012 Building choice of high quality support for commissioners
    91. 91. US is doing it! It is a shared enterprise of Harvard University, its ten schools and its eighteen Academic Healthcare Centers (AHC), as well as the Boston College School of Nursing, MIT, the Cambridge Health Alliance, Harvard Pilgrim Health Care and numerous community partners. Harvard Catalyst was founded in May 2008 with a five year, $117.5 million grant from theNational Institutes of Health (Clinical and Translational Science Center, CTSC) and $75 million dollars from the Harvard University Science and Engineering Committee, Harvard MedicalSchool, Harvard School of Public Health, Beth Israel Deaconess Medical Center, Brigham and Womens Hospital, Childrens Hospital Boston, Dana-Farber Cancer Institute and Massachusetts General Hospital. The resources of the Harvard Catalyst are available to all faculties at Harvard regardless of their institutional affiliation or academic degree.
    92. 92. Centre for innovation PlatformCollaborators DOBLIN PLATFORMS Prediction & Destination Culture & Mayo Clinic Wellness Prevention Mayo Clinic Competency Connection Experience Experience Experience of Innovation 95
    93. 93. Summary• Opportunities for Scotland to be world leading despite the current challenges and economic climate• Open innovation, embedded within NHS Boards a founding principle• Bring information science into the Board room• Could a more collaborative model between NHS and HEI partners add value?• Support Scotland‟s first National Outcome We live in a Scotland that is the most attractive place for doing business in Europe
    94. 94. The road ahead for the next few years “The only place where success comes before work is in a dictionary” V Sassoon, 1928-2012 “If we do not succeed,then we run the risk of failure” D Quayle, 1947- US Vice President
    95. 95. "In the middle of difficulty liesopportunity."
    96. 96. Thank you for listening!