F igh t ing Lou Gehr ig ’ s Di sease i n Mi ch igan

Inside this issue:

Keo’s Back from Bot-

swana

Meet Robbi!

2

CaddyAm raises funds

for ALS

ALS Drug Candidate in

development

3

ALS Association An-

nounces New Research

Grants

4

Chapter Calendar

Wheelchair Van

Available

5

Head Trauma and ALS

Feeding Tube Care

6

7

Registered Teams Roster

Scientists find new ge-

netic component

8

9

Order your ALS Aware-

ness Wristbands!

10

Volume 1, Issue 6 Seotember 2010

Counting Down to The Walk to Defeat ALS

11 Days Until…Jackson • 11 Days Until…Traverse City 18 Days Until…Portage

25 Days Until…Detroit • 33 Days Until…Grand Rapids

The ALS Messenger

Detroit Walk to Defeat ALS Grand Rapids Walk to Defeat ALS

Saturday, September 25, 2010 Sunday, October 03, 2010

Detroit Riverfront Conservancy Ah-Nab-Awen Park

Traverse City Walk to Defeat ALS Jackson Walk to Defeat ALS

Saturday, September 11, 2010 Saturday, September 11, 2010

Civic Center Park Ella Sharp Park

Portage Walk to Defeat ALS Virtual Walk to Defeat ALS

Saturday, September 18, 2010 Anytime

Celery Flats Anywhere

Visit www.WalkToDefeatALS.org to register your team TODAY!

The 2010 Walk to Defeat ALS is here. Join us as thousands across the state Michigan Walk to Defeat ALS. The Walk to Defeat ALS is a day of HOPE, day of REMEMBERANCE, and a day to

raise money to help get us one step closer to finding a CURE for Lou Gehrigs Disease.

Last year over 150 Walk to Defeat ALS™ teams participated across the State of Michigan.

Please consider joining The ALS Association in 2010 as a walk team or as an individual walker.

Teams are already making a difference in their local communities by raising dollars for ALS in creative ways::

- $5 Jeans Days at Work - Bake Sales - Letter Writing Campaigns - Car Washes - Lemonade Stands - Facebook - Tennis Matches Let us know how our walk team can support you. Most importantly, spread the work about

why you are walking. Share with others the name and story of the individual you are working for.

Robbie Banfill • Grand Rapids, Portage,

Traverse City • rbanfill@alsa-michigan.org • 616-459-1900

Joe Kulwicki • Detroit, Jackson, Virtual • jkulwicki@alsa-michigan.org • 866-927-CURE

Marie Tominna • Detroit • DetroitWalk@alsa-michigan.org • 866-927-CURE

The ALS Messenger Page 2

Meet Our Staff: Robbie Banfill, Special Events Coordinator

Troy Support Group Welcome Guest Moderator back from Botswana

can be found working in

her garden, volunteering

at her church or walking

her two boxer mixes.

Robbie is passionate

about helping our Michi-

gan PALS and has said

that since coming to

ALSA, she can ’ t imag-

ine leaving the non-profit

world.

Thank you Robbie for

your hard work and dedi-

cation to our PALS. We

are lucky to have you on

the team!

Robbie Banfill came to

the ALS Association,

Michigan Chapter a little

over two years ago after

spending time as a stay

at home mom to her son.

Working out of the Grand

Rapids office, Robbie is

our Special Events Coor-

dinator, overseeing many

events throughout the

year including the Grand

Rapids, Portage and

Traverse City Walks to

Defeat ALS, Rock and

Rumble Motorcycle Ride

for ALS, Caddy Jam

Benefit Concert,

CaddyAm Golf Tourna-

ment for ALS in addition

to helping virtual walkers

and lending a hand with

events on the east side of

the state.

Well loved by Chapter

staff for her technical

savvy, Robbie is con-

stantly in motion and

never without a smile.

When she ’ s not busy

planning an event or

helping the team, Robbie

Our Troy Support Group is happy to welcome Ms. Keolebogile Semphadile, an international doctoral student studying at

Oakland University, back from her summer in her native country of Botswana, Africa. Keo was kind enough to offer the

excellent and well-received ―Coping with A Loved One’s Illness‖ Seminar in the spring and has graciously agreed to re-

turn to the Michigan Chapter this fall as a guest moderator at our Troy Support Groups. Keo will address a new topic

related to coping and well-being each month throughout the fall.

Keo has over 20 years experience as a professional counselor and is currently pursing her PhD in Counseling with a spe-

cialty in Greif and Loss. She notes that while she hopes to teach our PALS and families more about stress, coping and

grief, that the experience of working with the chapter is helping her learn more about her own feelings these concepts. If

you would like to join us for one of Keo’s sessions, please let Kristen know you are able to attend so we can ensure we

have enough space to accomdate everyone. You can reach Kristen at 248-680-6540 or at kristen@alsa-michigan.org.

“There are times

when the emotional

or physical burden of

ALS can demand all

of a family’s focus,

and we understand. “

Walk When You are Ready, Seek Resources Now

you and your family would

like to find out more informa-

tion about the Walk to De-

feat ALS, we invite you to

call or email our offices. As

always, if there is anything

we can do assist you on your

journey with ALS, please

contact your Patient Services

Coordinator anytime!

This month you may notice a

lot of information about our

upcoming Walks to Defeat

ALS. While these are excit-

ing, wonderful days that can

bring families together for

the cause and inspire hope,

we understand that not eve-

ryone is ready to walk with

us this year. There are times

when the emotional or physi-

cal burden of ALS can de-

mand all of a family’s focus,

and we understand. We

want you to know that while

we hope you’ll walk with us,

participating in the Walk is

in no way required to re-

ceive assistance through our

Patient Services Program. If

Robbie Banfill

Special Events Coordinator

Grand Rapids Office

Page 3 Volume 1, Issue 6

Benefits for Veterans with ALS

Military veterans diagnosed with ALS who have served at least 90 continuous days on active duty will be consid-

ered service connected for ALS. This is the case regardless of when or where a veteran served in the military and

regardless of the length of time between discharge from the military and a diagnosis of ALS.

If you are a military veteran with ALS, you may be eligible to receive significant health and disability benefits from

the Department of Veterans Affairs (VA). That’s because on September 23, 2008, the Department of Veterans

Affairs established a presumption of service connection for ALS. This means that military veterans with ALS may

automatically be eligible for benefits that can include: monthly disability compensation, adaptive housing grants,

education assistance, and full health care to name a few. The ALS Association helped to lead the fight for this

policy and we now are working to ensure that every veteran with ALS can access these vital benefits as quickly

as possible.

Eligibility: In general, to qualify for benefits a veteran must have a diagnosis of ALS and must have served on

active duty for at least 90 continuous days. Veterans with ALS can qualify for benefits regardless of where

(domestically or abroad) or when they served in the military and regardless of when they were diagnosed with the

disease following military service.

Survivors and Families: Surviving spouses and families also may be eligible for benefits even if a veteran with

ALS passed away years or even decades prior to implementation of the ALS regulations in 2008. Benefits for sur-

vivors can include monthly compensation and medical benefits among others.

Information and Assistance: To learn more about these vital benefits, including answers to frequently asked

questions, eligibility requirements, and how to apply for benefits, please visit The ALS Association’s website at

www.alsa.org/policy/veterans.cfm.

If you are a veteran with questions about your benefits, please contact

Kristen at 248-680-6540 or Denise at 616-459-1900

The drug was

shown to have a

favorable effect

on extending

survival.

ALS Drug Candidate to Enter Stage 3 Program in 2011

This week an announcement was made by Biogen Idec and Knopp Neurosciences that they have

entered into an exclusive licensing agreement under which Biogen Idec with develop and commer-

cialize KNS-760704 (dexpramipexole). The drug was show to have a favorable effect in pre-

serving motor function and extending survival in patients with Amyotrophic Lateral Scerlosis. The

drug has received orphan drug designation from the FDA as well as Fast Track Designation. In the

Phase 2 study, the drug was found to be generally well tolerated.

Biogen Idec hopes to begin a Phase 3 program of the drug in early 2011. For more

information about this development, visit http://www.medicalnewstoday.com/

articles/198522.php.

The ALS Messenger Page 4

ALS Association Announces New Research Grants

The ALS Association, Michigan Chapter was excited to learn that a new cycle of grants were funded by The ALS Asso-ciation to contribute to the search for meaningful treatments and eventually a cure for ALS. This article can be found in its entirety at http://www.alsa.org/news/article.cfm?id=1666&CFID=6657493&CFTOKEN=fc602820c2f24b43-7C33E1C0-188B-2E62-806186710117324B The ALS Association has announced newly-funded research grants for the August 2010 cycle. Our TREAT ALS Portfo-lio (Translational Research Advancing Therapies for ALS) is a research endeavor enabling important research to pro-gress from the laboratory to the bedside. The focus of the program is to support novel ideas, build tools, partner with in-dustry to identify new potential therapies and support the infrastructure for clinical trials, with the goal to find meaningful treatments for ALS and a cure. In addition, through the Milton Safenowitz Post-doctoral Fellowship program, young scientists are encouraged to focus their interest in ALS research. New research studies funded this year will focus on areas of stem cell research, genetics, therapy development, biomarkers and neuroinflammation. Three new Milton Safenowitz Postdoctoral fellows will focus on the genes recently identified for familial ALS, TDP43 and FUS; new techniques to identify genes for familial ALS; and a novel triple transgenic mouse to identify the role of inflammation in ALS. Descriptions of the twelve funded projects are available on the ALSA National website at http://www.alsa.org/news/article.cfm?id=1666&CFID=6657493&CFTOKEN=fc602820c2f24b43-7C33E1C0-188B-2E62-806186710117324B. De-scriptions of two of the awarded grant proposals are detailed below.

Novel Surgical Approaches to Stem Cell Transplantation for ALS Clive Svendsen, Ph.D. Cedar-Sinai, Los Angeles, CA Presently there is one clinical trial at Emory University injecting stem cells produced by the company Neuralstem into the spinal cord of patients with ALS. This project uses a very invasive but accurate injection method where a frame is placed on the patient under deep anesthesia and a large portion of the spine is exposed in order to target the appropriate region for transplantation. This study, however, uses a much simpler and non invasive approach for stem cell delivery based on a modified lumbar puncture technique. An outer guide needle is positioned in close proximity to the spinal cord, and an inner needle con-taining the cells is pushed under imaging guidance into the target area and cells are then injected. The investigators have developed a clinical grade neural stem cell line that secretes a powerful growth factor, GDNF. They plan to inject these cells using this procedure in a number of pigs under conditions where the data can be used for presentation to the FDA and then progression to a clinical trial. Bone marrow-derived cells as gene delivery vehicles in ALS Charles Krieger, Simon Fraser University, British Columbia, Canada Fabio M.V. Rossi, Biomedical Research Center, University of British Columbia, Canada The use of bone marrow-derived cells as a novel therapeutic delivery system has considerable promise in the treatment of ALS. Bone marrow-derived cells can be injected into the circulation, and there is evidence from pre-clinical studies that these cells are capable of entering the brain and spinal cord under some conditions. The investigators’ previous work has shown that bone marrow cells enter the brain and spinal cord in an animal model of ALS. In this work they will engineer the population of bone marrow cells that enter the central nervous system to produce growth factors such as vascular-endothelial growth factor (VEGF) within the nervous system to permit delivery of growth factors directly to brain and spinal cord. They anticipate that these growth factors will aid in the survival of diseased neu-rons. They will identify which bone marrow-derived cell types enter the nervous system so that we can restrict the pro-duction of growth factors only to the specific bone marrow population that enters the nervous system. Knowing the rele-vant cell populations will allow them to restrict production of the secreted growth substances which will minimize the ad-verse effects of using the engineered cells.

The ALS Messenger Page 5

Wheelchair Accessible Van Available through Generous Donation

A result of a one PALS’ incredible generosity, The ALS Association, Michigan Chapter is able to announce the availabil-

ity of a 1995 Plymouth Voyager wheelchair accessible van for private donation to one of our Michigan PALS. The van

has 123,133 miles. The van has a ramp that is powered by a switch on the side of the van. It has a lowered floor with air

bags that raise it to driving height when put into gear. Due to lack of use, the van has a leak in its fuel line. Whomever

receives this van would need to incur the cost of this repair, in additional to all other expenses associated with the transfer

and subsequent ownership of the vehicle.

If you are interested in being the recipient of this donation, please email kristen@alsa-michigan.org or call the

Troy office at 248-680-6540 for an application for consideration. Applications will be accepted until 5pm on Wednes-

day September 8th. An application must be submitted for consideration. The recipient will be determined based on need

and notified by September 15th.

Sun Mon Tue Wed Thu Fri Sat

1 2 3 4

5 6 7 8 9 Call In 2-3

Troy SG 6:30-8pm

10 11

Jackson & Trav-

erse City Walk to

Defeat ALS

12

Grand Rapids SG

2-4pm

13 14 15 Kalamazoo SG

7-8:30pm

George Clark from

HandyMan Matters

presenting

16 17 18

Portage Walk to

Defeat ALS

19 20

Bay City SG 6:30

-8pm

21 Call-In 6:30-

7:30

22 23 Survivors Lunch

Gaylord SG 6:30-

8pm

24 25

Detroit Walk to

Defeat ALS

26 27 Flint SG 6:30-

8pm

28 29 30

September Chapter Calendar

The ALS Messenger Page 6

Respiratory Issues Conference: October 28, 2010

Respiratory Issues and Equipment

presented by Airway Oxygen Inc.

Mary Free Bed Rehabilitation Hospital

2nd floor conference room

October 28st

6:30pm-8:00pm

Please RSVP to Denise George at denise@alsa-michigan.org

or 616-459-1900 by October 21, 2010.

“More research

using a greater

number of cases are

required to produce

conclusive results.”

Researchers Investigate Head Trauma & ALS

quires further investiga-tion.” A further ALS Association publication notes that while patients with ALS have evidence of motor neuron degeneration, pa-tients with CTE do not. They believe Lou Gehrig did in fact have ALS, as he demonstrated clear motor neuron disease. This new study adds to the body of knowledge surrounding motor neuron disease, and points out that more research us-ing a greater number of cases are required to produce conclusive re-sults. To read the full New York Times article, visit http://www.nytimes.com/2010/08/18/sports/18gehrig.html?_r=1&emc=na

Researchers from Boston University are publishing a new study in the Journal of Neuropathology and Experimental Neurology on the relationship of head trauma and amyo-trophic lateral sclerosis (ALS). The researchers found toxic proteins in the spinal cords of the three athletes. Those same proteins have been found in the brains of athletes with chronic traumatic encephalopathy (CTE), a disease linked to head injuries that causes cogni-tive decline, abnormal behavior and dementia. Previous studies have linked TAR DNA-binding protein (TDP-43) to some familial forms of the dis-ease, and although etiol-ogy of sporadic ALS is unknown, it has long been suspected to involve a complex interaction be-

tween multiple genetic and environmental risk factors. Among the many environmental factors that have been considered as possible triggers of the neurodegenerative cas-cade in ALS are a history of trauma to the brain and spinal cord, participation in varsity athletics and a slim physique, and strenuous physical activ-ity. A New York Times article suggests that brain trauma can mimic ALS, and that perhaps Lou Ge-hrig may not have had the disease that bears his name. ALS Association Chief Scientist Lucie Bruijn is quoted in the article as saying, “It’s ex-tremely interesting - it builds a more interesting picture, but what this all exactly means about how the disease plays out re-

The ALS Messenger Page 7

Michigan Offers Extraordinary ALS Care

The following clinic is also

recognized by The ALS Asso-

ciation:

The MSU at Mary Free Bed Rehabilitation Hospital 360 Lafayette Suite 308 Grand Rapids, MI 49503

616-493-9727

ALS Patients living in Michigan have the ability to choose between sev-eral excellent ALS cen-ters to visit for their multi-disciplinary clinical care. With two certified centers of excellence and another clinic going through the process, there are many venues for treatment in Michigan. For more infor-mation on the clinic near-est to you, please contact your Patient Services Co-ordinator .

Michigan is home to the following certified centers:

Henry J. Hoenselaar Clinic Henry Ford Hospital Neurology K-11 2799 West Grand Blvd Detroit, MI 48202 313-916-2835 The University of Michigan Health System 1914/0316 Taubman Center

1500 E. Medical Center Dr Ann Arbor, MI 48109 734-936-9020

“A feeding tube

should be

completely

comfortable.”

Advice from the Trenches: Feeding Tube Care

water and Q-tips, remove the soapy fluid. And fi-nally dry the area with dry Q-tips. Do this every day. You can use apply gauze around the tube, but I suggest not using tape. The gauze will stay in place if the split is on the bottom side of the

tube.

If you have a length of tube lying on your abdo-men, I find it convenient to loop the tube in a loose knot when not being used. This keeps it from inadver-tently being pulled during

transfers.

As a precaution, it’s best to take an acid reducer. It’s very easy for stomach acid to enter the tube tract. A feeding tube should be completely com-fortable. If you feel burn-ing or pain, this may be

the cause.

Sandra Lesher Stuban is an RN who was a 38-year old Lieu-tenant Colonel in the Army when she was diagnosed with ALS. She’s the author of ―The Butcher’s Daughter: The Story of an Army Nurse with ALS,‖ in which she describes her journey openly and honestly. Although she is completely paralyzed and uses a ventilator, she lives an active life as a writer, nurs-ing leader and mother of a

teenage son.

Q: I am having more difficulty swallowing. I think I will soon need a feeding tube. But I am nervous and feel like I am los-ing my fight against ALS. Do you have any advice? A: A feeding tube, also known as a PEG (percutaneous endo-scopic gastrostomy) or g-tube (gastric tube), is actually your way to win this one battle against ALS. ALS isn’t defeating you, rather you are defying its paralyzing effects by using a simple comeback – the feeding

tube. You can also look at a feeding tube as a pair of glasses. You could do without it but why make yourself miserable. Here are some general tips for living well with a feeding

tube.

I am an advocate of keeping things simple. I know some people insist on pureeing the same food the family eats. However the same family mealtime dynamics can occur whatever the food choice. Therefore I recom-mend a liquid total nutri-tion meal such as Isocal, Nutren, Osmolite, and oth-ers. Plus it’s much easier

for your loved one.

Caring for a feeding tube is very easy. Simply mix a few drops of liquid anti-bacterial soap with warm water then use a Q-tip to clean the skin immediately beside the tube. Using tap

ALS Association Certified CentersSM

are medical facilities that have been certified by The Association as distin-guished regional institutions recognized as the best in the field with regard to knowledge of and experience with ALS

The ALS Messenger Page 8

Thank You to All of 2010 Walk to Defeat ALS Registered Teams!

The following teams have committed to participate in one of the 2010 Walk to Defeat ALS loca-

tions. Thank you for your dedication to fighting ALS with us!

Allens Allies GR Myrna,s Legacy TC

ALSAWest DT One Step at a Time DT

Annie's Hope PO Outliers Against ALS DT

Athlete's Feat GR Pardee for PALS DT

B3 - Beyer's Bodacious Bunch GR Peaches ~N~ Creame DT

Barbie's Crane Train GR Peggy's Pals PO

Benny's Buddies DT Poma's Posse DT

BHS Alumni Rally for Lynn GR Quicken Loans DT

Blaze Man PO Roger's Dodgers TC

BlueWater Technologies DT Ruthie's Warriors PO

Bouma-JJ's Foot Soldiers GR Ruthie's Warriors GR

Brian's Bullpen PO Sallys BARn on a mission DT

Chase Bank - Suburban Detroit Group DT Sally's Footprints GR

Chris' Crusaders GR Sophia's Sidekicks DT

Chuck's Commando's DT Spunkie Ankie TC

Compuware DT Strides for Stuif PO

Conly's for a Cure DT Team Dale DT

Connie's Clique GR Team GR GR

Craig's Crew/Miss Mattawan Scholarship Program PO Team Jana Wood DT

Curt's Crusaders JK Team Mary Lou PO

Dawn's Divas GR Team Moceri DT

Debbie DT Team Pablo GR

Gran's Girls DT Team Ratliff DT

Gryffindor for the Cure PO Team Regis DT

Harriet's Helpers PO TEAM REOCH II PO

Jean's Team DT Team Rhythm Pointe DT

Jeffrey Pate vs. Lou Gehrigs Disease VW Team Sharon Johnson GR

Jeffs Gang DT Team Taggart GR

Joseph's Angels JK Team Tison DT

Julie's Street Walkers PO Team Troy DT

Ken's Friends DT Team Troy GR

Kids for a Cure DT Team Ureel DT

Lake Michigan Credit Union-Joggin for Joe GR T's Team PO

Lake Orion Early Childhood Program DT vests hope for a cure GR

Mama's Girls TC Vitas DT

Mary's Girls DT Walking for Larry GR

Maui Time DT Walt's Winning Warriors DT

Metro-West Appraisal Co. DT WCCCD Bookstore DT

Miracle Awareness Team GR Willi/Gould Gang PO

Mr. Roger's Friends PO Willis/Gould Gang GR

DT= Detroit Walk; GR= Grand Rapids Walk; PO= Portage Walk; JK= Jackson Walk; TC= Traverse City

The ALS Messenger Page 9

RESEARCH UPDATE: From The ALS Association, National Office

August 26, 2010

Study Identifies New Genetic Risk Factor for Lou Gehrig’s Disease

An international study led by biologists and neuroscientists from the University of Pennsylvania, published this week in Nature, has identified a new genetic risk factor for amyotrophic lateral sclerosis, which is commonly known as ALS or Lou Gehrig’s disease. Using yeast and fruit fly as simple, yet rapid and powerful models, and then following up with human DNA screen-ing, the team found evidence that mutations in the ataxin 2 gene were a genetic contributor to the disease. More specifically, the study shows that expansions of a run of the amino acid glutamine in ataxin 2 are associated with an increased risk for ALS, with a frequency of 4.7 percent of ALS cases examined. The identification of pathological interactions between ataxin 2 and TDP-43, another ALS-associated disease pro-tein should aid in the development of biomarkers and empower the development of new therapies for this dis-ease. Results of the study were confirmed in fruit fly models, in biochemical analyses, and in human cells, revealing that ataxin 2 is a potent modifier of TDP-43. The study showed that ataxin 2 and TDP-43 interact in animal and cellular models in a manner to promote pathogenesis. ―This is a very exciting study using a novel approach to identify risk factors in ALS,‖ said ALS Association Chief Sci-entist Lucie Bruijn, Ph.D. ―The association between TDP-43 and ataxin 2 is intriguing and further studies will hope-fully shed more light on how these interactions are linked to ALS.‖ The results indicated a link between the proteins and the disease. For example, when the researchers directed expression of TDP-43 to the eye of the fruit fly, a progressive, age-dependent degeneration began. When di-rected to the motor neurons, flies experienced a progressive loss of motility: the higher the levels of ataxin 2, the greater the toxicity of TDP-43, resulting in more severe degeneration and the less the amount of ataxin 2, the less the toxicity. ―Because reducing ataxin 2 levels in yeast and flies was able to prevent some of the toxic effects of TDP-43, we think that this might be a novel therapeutic target for ALS,‖ said study co-senior author Aaron Gitler, Ph.D., assis-tant professor of Cell and Developmental Biology at Penn’s School of Medicine. The ataxin 2 gene had previously been implicated in another neurodegenerative disease called spinocerebellar ataxia 2, or SCA2. Ataxin 2 contains a repeated stretch of the amino acid glutamine, abbreviated Q. This tract, called polyQ, is usually short, only about 22 or 23 Qs. However, if the polyQ tract expands to greater than 34 Qs, patients develop SCA2. The new results show that intermediate-length polyQ repeats, between 27 and 33 Qs, longer than normal but shorter than what causes SCA2, increase a person’s risk for developing ALS. Our findings do not mean that if you have 27 Qs or more in your ataxin 2 gene that you will definitely get ALS, only that it increases risk for it,‖ Gitler added. ―However, the identification of a novel and potentially common ALS disease gene from a simple yeast screen, leveraged by the more complex model created in fruit flies, under-scores the extraordinary power of yeast and fly as model systems for gaining insight into human disease patho-genesis.‖

Create Awareness with an ALS Wristband!

675 E. Big Beaver, Suite 207 678 Front Street, Suite 159

Troy MI, 48083 Grand Rapids, MI 49504

The ALS As soc ia t io n , M i ch igan Cha pte r

People with ALS and their families come first in everything we do. Our vision is a world without ALS!

FIGHTING LOU GEHRIG’S DISEASE

Fighting Lou Gehrig’s Disease red wristbands are

available through our offices. These red silicone bands

make a unique statement and create awareness. They

are available at a recommended donation of $2 per

band. Please call your local office for more informa-

tion on getting your wristband!

Troy—248-680-6540

Grand Rapids—616-459-1900

Phone: 248-680-6540 616-459-1900

Fax: 248-680-6543 616-459-4522

Email: kristen@alsa-michigan.org denise@alsa-michigan.org