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Transcript: 1860 http://www.uihealthcare.com/topics/medicaldepartments/neurology/huntingtonsdisease/overview.html Charles Davenport Dementia that gets worse Disorientation Loss of judgement Loss of memory Personality changes Speech changes Additional symptoms Anxiety, stress, tension Symptoms in children Rigidity Slow movements Tremors So what do you think this repeat would do to gene function? 1911 Transcriptional dysregulation Protein misfolding and degradation Impairment in intracellular transport, mitochondrial function and synaptic transmission. http://www.stanford.edu/group/hopes/cgi-bin/wordpress/2010/06/the-cognitive-symptoms-of-huntingtons-disease/ Post translational modification-acetyl tag signal SirT1 inhibition, Selisistat Phosphodiesterases inhibitors: PDE 10 and 4 now in testing Gene silencing Stem cell generation of neurons Bruproprion Manipulation of synaptic activity - Memantine Ch Implications of HD http://atlasfolding.com/?page_id=51 Current Therapies https:///nm/journal/v10/n7s/full/,DanaInfo=www.nature.com+nm1066.html Genetic Testing Why Test Mid Stage 1872 Works Cited Amber Johnson, Hannah Killian, Sarah Tamura https://www.stanford.edu/group/hopes/cgi-bin/wordpress/2010/06/the-inheritance-of-huntingtons-disease-text-and-audio/ Basic Symptoms http://schoolworkhelper.net/huntingtons-disease-causes-symptoms-testing/ Mood changes Movement changes Cognition changes Two Forms Huntington's Disease Alzheimer's disease Parkinson's disease Amyotrophic lateral sclerosis (ALS) Prion diseases (CJD kuru etc.) Lose ability to speak and respond Chorea Lose ability to work, drive, perform activities of daily living Difficulties with balance and motor tasks Difficulties with processing information Irritability, aggression, depression Can be done safely More serious than a simple blood test Challenging psychological and social aspects Genetic Information Non-discrimination Act (May 21st 2008) Medical Value? Testing of Minors Anonymous Testing Testing of individuals at 25% risk 1846 Over 80 testing centers nation wide Emotional and ethical issues that come with HD diagnosis - no treatment to delay onset of HD symptoms, cannot cure HD Psychological support is very important ~ 10-20% of people at risk for HD request testing Grade 0: appears indistinguishable from normal brains after gross examination. Grade 1: shows atrophy in the tail, and in some cases the body, of the caudate nucleus. Grade 2: is associated with striatal atrophy that is more pronounced than that detected in grade 1 brains. Grade 3 displays severe striatal atrophy. Grade 4 includes HD cases with severe atrophy of the striatum and up to 95% neuronal Confirmatory/Diagnostic Testing Predictive Testing Prenatal Testing Grading Based on pattern of Striatal Degeneration Stages 1-2 http://www.nature.com/nrn/journal/v5/n5/fig_tab/nrn1386_F1.html Huntington's vs. Neurodegenerative Diseases Adult-onset : most common ages 30 to 50 Early-onset: small number of cases Worsen in 10-25 year period 1 in every 10,000 Americans has HD and more than 250,000 are at risk Most common hereditary disease Behavior Behavioral disturbances Hallucinations Irritability Moodiness Restlessness or fidgeting Paranoia Psychosis Abnormal movements Facial movements Head turning Jerking movements of arms, legs, face etc Slow uncontrolled movements http://www.cumc.columbia.edu/psjournal/sites/juno.cumc.columbia.edu.psjournal/files/Huntington.jpg Johan Christian Lund Dr. Huntington Late Stage Ambrose, C. M.; Duyao, M. P.; Barnes, G.; Bates, G. P.; Lin, C. S.; Srinidhi, J.; Baxendale, S.; Hummerich, H.; Lehrach, H.; Altherr, M.; Wasmuth, J.; Buckler, A.; Church, D.; Housman, D.; Berks, M.; Micklem, G.; Durbin, R.; Dodge, A.; Read, A.; Gusella, J.; MacDonald, M. E. "Structure and expression of the Huntington's disease gene: evidence against simple inactivation due to an expanded CAG repeat". Somatic Cell & Molecular Genetics; 1994, 20: 27-38. Conforti, P., Camnasio, S., Mutti, C., Valenza, M., Thompson, M., Fossale, E., . . . Cattaneo, E. (2013). Lack of huntingtin promotes neural stem cells differentiation into glial cells while neurons expressing huntingtin with expanded polyglutamine tracts undergo cell death. Neurobiology of Disease, 50, 160-170. doi: 10.1016/j.nbd.2012.10.015 Giampà, C., Laurenti, D., Anzilotti, S., Bernardi, G., Menniti, F. S., & Fusco, F. R. (2010). Inhibition of the striatal specific phosphodiesterase PDE10A ameliorates striatal and cortical pathology in R6/2 mouse model of huntington's disease. PloS One, 5(10), e13417. Gil, J. M., & Rego, A. C. (2008). Mechanisms of neurodegeneration in Huntington’s disease. European Journal of Neuroscience, 27(11), 2803-2820. Graul, A. I., & Prous, J. R. (2005). Executive summary: nicotine addiction. Drugs of Today, 41(6), 419. Ho, L. W.; Carmichael, J; Swartz J; Wyttenbach A; Rankin J; Rubinsztein DC. "The molecular biology of Huntington's disease." Psychologocial Medicine; 2001, 31(1): 3-14. Huntington’s Outreach Project for

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Transcript: From no voice, to a voice, to (hopefully!) an interesting voice RCM Policy Journey 1 Joint Policy initiatives Joint Policy Work ICRC+ IFRC with NS URBAN: Joint approach UN Habitat process, new urban agenda, multilateral forum. ICRC/IFRC common set of agenda points. URBAN MIGRATION: Joined up approach on migration w strong NS support. “Red footprint” emerging in UN Global Compact on Migration MIGRATION LOCALIZATION : Coordinated prep and advocacy at WHS "Istanbul and Beyond" Report LOCAL ACTORS IHL, Protection and Positioning of ICRC and its mandate ICRC Priorities ICRC (Hugo Slim and Team) Esp Compliance track leading up to 33rd Int'l Conference Sucess in negotating compliance language at recent G7 Meeting in Toronto CRC work aimed at reinforcing this Affirm IHL IHL Increase protection language through strategic diplomacy efforts and improve States' policies and engagement on missing people, IDPs, migrants and detainees Protect People Better PROTECT PEOPLE Shape policy on new forms and fields of humanitarian action Meet changing needs in protracted conflict, urban warfare, urban violence, autonomous weapons, digital warfare (new position) Shaping Humanitarian Practice SHAPE PRACTICE Convince stakeholders of real improvements on accountability and in diversity, gender and inclusion. Prove relevance of the ICRC to major and middle powers esp. in Asia, support and enable the ICRC humanitarian mission, at a time of reordering global structure. ICRC Positioning POSITION ICRC Localization, Migration, Climate and Disaster, Health IFRC Priorities IFRC (David Fisher and Team) Driving climate and disaster policy toward resilience, early action and the most vulnerable CLIMATE AND DISASTER CLIMATE AND DISASTER Reaching the last mile, and universal coverage through community health (WHO focus on community health workers syncs well with RCM work) HEALTH HEALTH Protecting vulnerable migrants and displaced people VULNERABLE MIGRANTS MIGRATION Localization Pooled Funds Work Streams of Grand Bargain NWOW/ Humanitarian Development Nexus Invest in Hum Actors RED PILLAR HD Tools and Venues 2 #1 International Conference (33rd IC Dec 2019) #2 Mvm't Publications WDR, Int'l Review of RC, joint topical reports (often led by interested NS) #3 Multilateral fora and processes (GB workstreams, observer status at UN, EU, Arctic Council) CRC Push F4P Mandate- Strong profile w/in Movement with an aim to support operations What does it take to get right people, with right skills, in right place, at right time? HD in Operations HD in Emergencies HD Capacity Strengthening For ourselves, what are the tools needed to support Competency framework? What have our sucesses been in Capacity Strengthening? Is this an area to explore more deeply with long term partners? Capacity Strengthening Opportunities Already piloted at CRC-Social Emergencies Workshop Interest in support to roll out in Americas, and beyond HD workshop Training Tools Current group not fully representative- can we pick 2? Support participation and engagement in Policy Group? Ways to engage others in a "engage before/ brief back" model? Bring interested partners into Policy dialogue Engaging Partners Engage Partners and keep them up to date on themes and prep Pledges together with Can Gov (Missing Migrants already in prelim discussion) Events/ workshops linked to themes? Gender and xx? International Conference 33 IC HD capacity strenthening HD context mapping and support IHL context analysis IHL as a project component for NS (a few caveats) Support to programs HD in OPS Case studies to share and profile our learning Identify areas where we want to drive thinking within the Movement or beyond Lead a research area Knowledege Generation Ways we are already engaging that we may not be fully leveaging? Other Opportunities? OTHER? ? Question Time? Onward and upward with coherence !

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Transcript: John Muir and National Parks Manifest Destiny- The belief that American settlers were bound to expand across the continent Westward Expansion- As more and more claimed and unclaimed land became available to take (including the Louisiana and Indian territories), thousands of settlers immigrated to the west in the hopes of getting a better chance of living. 1851, The first white men enter the Yosemite Valley,California, arrive. They were an armed battalion whose aim was to search for Native Americans and drive them from their homeland. One of them, Lafayette Bunnnel was struck by its beauty and suggested they give it a name. Believing it was the name of the Native American tribe living there, they called it Yosemite. John Connes, a junior senator from California, introduced a bill to congress in 1864 which set a large tract of "natural scenery" for the future enjoyment of everyone (Yosemite Grant). It was to be given to the state of California, under condition that the land be used by the public. This was the first step in making Yosemite a government protected land. Yellowstone, 1872- Ferdinand Hayden and a group of a scientists traveled to Yellowstone. They came to the Congress with information stating that the settlers were unable to farm and mine in Yellowstone. Hayden also warned that if the Congress did not take Yellowstone from private development, it would turn into another Niagara Falls.Yellowstone was then made into the world's first national park. Years later, the prime attractions in Yellowstone were in grave danger of being exploited. The park had no protection. Though, in 1875,Troop M of the U.S. cavalry took control of the park and saved it from further exploitation and harm. John Muir was very important in the establishment of national parks. Born in Scotland in 1838, John Muir immigrated to Wisconsin, U.S.A. with his family when he was 11 years old. Muir worked as a homesteader and labored on a farm. He disliked the work conditions, and as a result, he worked in a factory. However, he was partially blinded by an accident while working there and choose to study the natural sciences instead. Muir visited Yosemite in 1868, and he was in such awe at the wilderness that he decided to come back again and work as a rancher to herd sheep in the Tuolumne Meadows. The following year when Muir came back, he sketched several drawings of the mountainous and flowery scenery. During the years Muir wrote, he published articles on nature and the environment. His knowledge and aptitude of the subject tremendously grew proportionately to his interest and care for the wilderness. For example, in the 1880’s, Muir looked into environmental damage of Yosemite and found out that the area was littered by trash, destroyed by livestock, and altered into meadows for growing hay. In an effort to stop this, Muir persuaded the editor of Century magazine, Robert Johnson, to put out the suggestion of making Yosemite a national park so it would be protected by the federal government. Johnson's publications of Muir’s views convinced the Congress to officially make a bill stating that the area around the Yosemite Grant was a national park. The next year, Muir’s dreams came true; the Yosemite National Park became a reality. On October 1, 1890, President Benjamin Harrison signed the bill that made the Yosemite area a National Park. Deforesting and poaching did not end; Muir's will to stop it also did not cease. He tried to gain support from several people, including the future president, Theodore Roosevelt. Before his presidency was over, Roosevelt helped create dozens of units that preserved the wildlife. National Parks and Western Expansion- As the Unites States expanded west, the need for housing and resources increased. This caused many habitats to be destroyed and harvested for their natural resources as well as for land to settle. A few reasons for creating national parks include refuges for animals that would otherwise go extinct as well as supporting the idea that the natural wonders of the U.S should be available to not just a select few but to everyone. Men such as John Muir have the intention of preserving nature as civilization moves west and giving the public the option to observe nature that might have been destroyed or owned if not for the establishment of National Parks. The Conservation of Biodiversity Help Scientists Measure Climate Change Culture of Those who Lived Before Us Public Enjoyment Economic and Social Values Lasting Effects Ever since Yosemite was discovered, it has has greatly contributed to America's (and the world's) wealth of knowledge. Research and studies have been going on about the animals, insects, geology, and plants in the area for centuries. Lots of the information gathered from these works have also been published in an online database called the Yosemite Science: Innovations in Research & Resource Management. For basic understandings, information is published in the monthly Yosemite

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