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Page 1: Lindsay Grace Portfolio

lindsaygracePortfolio 2014

Page 2: Lindsay Grace Portfolio
Page 3: Lindsay Grace Portfolio

BROOKFIELD ZOOWelcomes You

to the GRAND OPENING of the

BUTTERFLYEXHIBITION

MARK YOUR CALENDARS May 20th 2010 at 10:00am

and come celebrate with us at our ribbon cutting ceremony.

Located on First Avenue in Brookfield IllinoisFor more information contact us at our guest line

(708) 688-8000 or visit us at our websitewww.brookfieldzoo.org

ZOOPresents:

BROOKFIELD

ZOOPresents:

BROOKFIELD

ADDYaward winner

2009

Project: Brookfield Zoo InvitationGoal: Conceptualize an original event then create an invitation and thank you card. Artwork was hand-drawn and then made digital.

Invitation Thank You Card

Page 4: Lindsay Grace Portfolio

2012BFA Senior Capstone

SHOWINGOFF

MOVINGON&

&Graphic Arts

Portfolio Show

April 6 – May 4 April 6, 4 – 6 Award Ceremony May 5, 4 – 5 Closing Reception

Admission is Free M – F: 10 – 3

A capstone exhibition featuring graduating seniors in the School of Design and Fashion

BFA Senior Capstone& Graphic Arts 2012 Portfolio ShowDavis Art Gallery Stephens College

Gallery located Corner of Walnut & Ripley. Email Dan Scott at [email protected] for Info

Designed By: Lindsay Iverson

Project: BFA Senior Capstone Gallery ShowGoal: The poster and postcard used to promote the actual exhibition of senior BFA students capstone and portfolio pieces. Show- casing my photography and photo manipulation.

PosterPostcard: Back

Postcard: Front

BFA Senior CApStone & GrAphiC ArtS 2012 portFolio Show

ShowinGoFFMoVinGon&

A capstone exhibition featuring graduating seniors in the School of Design and Fashion

April 6, 4 – 6 Award Ceremony May 5, 4 – 5 Closing receptionGallery located Corner of Walnut & Ripley Email Dan Scott at [email protected] for Info

April 6 – May 4Admission is Free M – F: 10 – 3 (or by appt)

Davis Art Gallery Stephens College

Designed By: Lindsay Iverson

Page 5: Lindsay Grace Portfolio

Art i

n th

e Pa

rkEx

perie

nce

the

Mag

ic

June 5th – 6th, 2010Sat 10am–5pm | Sun 10am–4pm

Stephens Lake Park

For a complete list of artists and performance schedules visit artinthepark.missouri.org or call Columbia Art League at 573-443-8838

June 5th–6th, 2010Sat 10am–5pm | Sun 10am–4pm

Art i

n th

e Pa

rkEx

perie

nce

the

Mag

ic

Project: Art in the ParkGoal: Design an advertising campaign for Columbia, Missouri’s annual summer art festival. Runner up. Art work is hand drawn and then was made digital.

Poster Program

T-Shirt

Page 6: Lindsay Grace Portfolio

Project: Hands for HopeGoal: Conceptualize and execute a passion project that had the capability of reaching a global market. Hands for Hope is a fictitious art therapy program for homeless youth.

PosterBannerWebsite

HANDS HOPEfor

HOME ABOUT US PROGRAMS EVENTS RESOURCES CONTACT

EVENTS

Grand Opening: June 8Opening Ceremony and Ribbon-Cutting at 6:30 pm

live music, appetizers and refreshments to followsilent auction and raffle at 8 pm

TORN: June 25-July14Opening Night June 25 at 7 pm

A look into the minds, hearts and souls of our youth ages 10-24 in a series of murals depicting there stories and daily struggles

4625 North Clifton Avenue, Chicago, IL 60640 (773) 367-4673

HANDS HOPEfor

HANDS HOPEfor

T-Shirt

Page 7: Lindsay Grace Portfolio

Interior Spread

Harbinger2012

f u l l d isc l o sure

Stephens College

Harbinger

2012

First place winner in the 2009, 2010 and 2011 Literary Arts Journal category.

Sigma Tau Delta International English Honors Society

“Stephens College is bursting with engaged and interesting young writers, and Harbinger is an excellent vehicle for all of that talent.”

Gabriel Fried, Poetry EditorPersea Books

“Looks good, reads great. One of the best showcases of young talent I’ve seen.”

Speer Morgan, EditorThe Missouri Review

“Working on Harbinger as a student at Stephens, I learned the fundamentals that would later inform my entire career.

I look forward to seeing the new edition every year!”

JenWoods, EditorTypecast Publishing

“Imaginatively designed and packed with superb writing, Harbinger is

always a pleasure to behold.”Andrew Leland, Editor

the Believer

60 61

Cla

wso

nN

on-F

ictio

n

Non

-Fic

tion

Cla

wso

n

dad takes up the entrance of my bedroom. “Get up now!” There is no arguing with that statement. My

dad’s heavy footsteps make the house shake. I leap from beneath the covers and begin my beauty regiment.

It is 9 a.m. on Saturday. My dad is a pretty laid-back guy, but when his voice grows hot with frustration, you don’t mess around.

I close my door, but it is stuck on something. I pull a bit more, and I hear wood scraping metal. The door stopper went through the door when Dad pounded on it.

I walk up the stairs and into the ’70s-style kitchen with a green exhaust fan and red-and-yellow wallpaper. My dad is nowhere to be found, but my sister Jennifer is at the kitchen table eating a bowl of Cocoa Puffs. She wears her tomboy clothes: baggy shorts and oversized T-shirt. This means yard work.

“Lucky tore up the tent,” she says. I look out the window. A pile of fabric sits in the middle of the

yard. The night before we put up our dad’s tent. We played in it and practiced our Brownie Girl Scout skills. Apparently the posts weren’t in the ground far enough. It blew into Lucky’s area. The tent didn’t stand a chance.

My brother Patrick receives his brand new electric wheelchair today. Bye to the old blue cruiser of grade school and hello to a new red one for high school.

He eases the joystick forward, and the chair inches forward. He moves it to the right; the chair moves to the right and the same for the left. Then he moves the joystick backwards and the chair follows.

Everyone comes out for this event; Mom, Jen, Dad, the tech guy who brought it over, and me.

Now to introduce obstacles into the equation. My brother spins

the chair around to face the opening into the kitchen. He moves from the center of the living room, around the sofa and into the kitchen area. He bumps the wall. Today there is still a dent in the drywall.

Next test, can he get into his bedroom? Most door openings made in the ’70s didn’t have wheelchairs in mind, especially not electric wheelchairs with protruding wheels. My dad widened Patrick’s door when he got the blue cruiser, but it was time to see if the red is a good fit.

Patrick inches right. His foot plates scratch the door. He stops, readjusts, and then tries the turn again. His arm rest hits. Patrick moves the chair back into position, but with a little more forward this time. He slides in.

“He’s in!” I yell to the crowd of people in the kitchen. They are watching from the outside while I got to experience it from the front row because I have claimed his bed as my viewing spot. My brother spins around to face me.

“The doors a bit dinged up,” he says.

“You have a big nose.” “You’re ugly.” “You could lose some weight.” Middle school is rough. Jennifer comes home every day with a

new insult for me. I just let her attack, but when she tries to control my actions the fight is on.

“This show is stupid. Change the channel,” she says, lounging on the sofa. I prefer the love seat; it is cozier.

“It’s off in ten minutes.” “Change the channel!” she yells. I play opossum. “I said change

the channel!” I don’t move. She gets up. I put the remote under me. She

Project: Harbinger Literary MagazineGoal: Design a cover, interior template, and layout a 100+ page book based on a theme decided upon by student editors and contributors.

Back and Front Cover

Page 8: Lindsay Grace Portfolio

Oct. 28-29 Nov. 4-5 7:30 p.m.

Oct. 30 2 p.m. Sunday Matinee

Macklanburg Playhouse100 Willis Ave.

$14 General$7 Student/Senior

THE STEPHENS COLLEGE PLAYHOUSE THEATRE COMPANY PRESENTS

Stephens College Box Office(573) [email protected]/performingarts

5464

HOUSE OF BLUE LEAVES

Special Thanks to Our Performance Sponsor: Watkins Roofing And Season Sponsors: KFRU News Talk 1400 AM & Joe Machens Dealerships

By John Guare

THE

HOUSE OF BLUE LEAVES

THE STEPHENS COLLEGE PLAYHOUSE THEATRE COMPANY PRESENTS

Special Thanks to Our Performance Sponsor:

Watkins Roofing

Macklanburg Playhouse

100 Willis Ave.

General $14 Student/Senior $7

Stephens College Box Office(573) [email protected]/performingarts

OCTOBER 28-30, NOVEMBER 4-5Fri–Sat 7:30 p.m. | Sun Matinee at 2 p.m.

And Season Sponsors: KFRU News Talk 1400 AM

& Joe Machens Dealerships

By John Guare

THE

Project: The House of Blue LeavesGoal: Manage the ad campaign forStephens College School of Performing Arts show for my internship. Half painted, half manipulated image in Photoshop.

PosterNewspaper Ad

Website Banner

Page 9: Lindsay Grace Portfolio

CIRCLE

MIRROR

TRANS-

FORMATION

BY ANNIE BAKERSept. 23-24 Sept. 30-Oct. 1 7:30 p.m.

Sept. 25 2 p.m. Sunday MatineeMacklanburg Playhouse

100 Willis Ave.

Special Thanks to Our Performance Sponsor: McDonald’s And Season Sponsors: KFRU News Talk 1400 AM & Joe Machens Dealerships

$14 General$7 Student/Senior

THE STEPHENS COLLEGE PLAYHOUSE THEATRE COMPANY PRESENTS

Stephens College Box Office(573) [email protected]/performingarts

5464

WWW.STEPHENS.EDU/PERFORMINGARTS

$2 OFF ANY TICKET FOR ANY PERFORMANCE(Mention “Columbia Welcomes You” at the Box Office)

FORMATION

CIRCLE

MIRROR

TRANS-

BY ANNIE BAKERSEPT. 23-25, SEPT. 30-OCT. 1Fri–Sat 7:30 p.m. | Sun Matinee at 2 p.m.

THE STEPHENS COLLEGE PLAYHOUSE THEATRE COMPANY PRESENTS

Special Thanks to Our Performance Sponsor:

McDonald’s And Season Sponsors:

KFRU News Talk 1400 AM & Joe Machens Dealerships

Macklanburg Playhouse100 Willis Ave.

General $14Student/Senior $7

Stephens College Box Office(573) [email protected]

5463

Project: Circle Mirror TransformationGoal: Manage the ad campaign for Stephens College School of Performing Arts show for my Internship. Showcasing my photography.

Poster

Newspaper Ad

Website Banner

Page 10: Lindsay Grace Portfolio

89 West Main Street, Suite 101 West Dundee, IL 60118

p 847.844.8640F 847.844.8670

www.RxCreativeLab.com

Focused, holistic communications for medical associations.

Lindsay Grace Graphic Designer 89 West Main Street, Suite 101 West Dundee, IL 60118

P 847.844.8640

F [email protected]

Art + ScienceA new perspective on medical design.

www.RxCreativeLab.com

Focused, holistic communications for medical associations.

Project: RxCreativeLab Re BrandingGoal: Design a new logo and brand based on the repositioning of the company to focus on designing for medical associations.

Letterhead

Direct Mail

Website

Business Cards

Logo (Backgrounds and text colors change)

Page 11: Lindsay Grace Portfolio

Project: Chicago Asthma ConsortiumGoal: Design a new brand for a chicago-based non-for-profit. Develop a logo and carry a brand theme through multiple design pieces.

Business Cards

Website

Brochure

Letterhead

Enhancing Lives Through Advocacy, Education and Collaboration

PO Box 31757, Chicago, IL 60631 • Phone: 888.268.8334 • Fax: 773.628.7663 • www.ChicagoAsthma.orgStacy Ignoffo, MSW

Executive Director

PO Box 31757, Chicago IL 60631

Phone: 888-268-8334 Fax: 773-628-7663

Direct Line: 773-628-7663

Email: [email protected]

www.ChicagoAsthma.org

Enhancing Lives Through Advocacy,

Education and Collaboration

Enhancing Lives Through Advocacy, Education and Collaboration

PO Box 31757, Chicago IL 60631 Phone: 888-268-8334 Fax: 773-628-7663

www.ChicagoAsthma.org

Your continued support is what allows us to strengthen our efforts to engage the asthma community, build stronger partnerships with key research and academic resources, educate and collaborate with our many stakeholders, and ultimately better the lives of those afflictedwithasthma.

Once you become a member, you can receive:• The opportunity to participate in Chicago’s only group of asthma advocates

• Access to the leading experts in the asthma community and the latest asthma news and information

• Discounts on CAC activities, resource materials and educational events

• Access to the Members-only section of the website, which includes the CAC Member Listserv, Bulletin Board and Job Bank

• Invitations to participate in a CAC Task Force;

• And much more!

Simply visit our website at www.ChicagoAsthma.org and get involved today!

Get Involved. Stay Involved.

Membership in the CAC is open to individuals and organizations active in and seeking to

improve the quality of life for people with asthma.

The Chicago Asthma Consortium is a coalition of medical and public health professionals, business leaders, government agencies, community-based organizations, and individuals dedicated to improving the quality of life for people with asthma through networking, information sharing, education, and collaboration.

Mission

The Chicago Asthma Consortium brings together the asthma community to improve the quality of life for Chicagoans living with asthma.

Purpose

• Raise awareness of patients, health professionals and the public that asthma is a serious disease.

• Promote a partnership among patients and health care providers through best-practice treatment and education programs.

• Facilitate a collaboration among healthcare professionals to identify resources available in the community to appropriately diagnose and better manage asthma.

• Encourage asthma patients, regardless of income, color, gender, creed, language or disability, to enter into continuing care by facilitating access to care.

Goals

Leading the effort in asthma education.

Another way to help those with asthma is to arm our key

stakeholders, Chicago-area doctors, nurses, pharma-

cists, respiratory therapists, public health professionals,

and community members, with as much educational

information and programs as possible. To accomplish

this, CAC:

• Implements regional educational and networking

meetings to provide information on cutting-edge

topics related to asthma care

• Leads discussions on emerging research

findingsandf

uturedirectio

nsinresearc

h

• Convenes a Community Advisory Board to

engage patients, caregivers and others concerned

about asthma

• Educates schools and caregivers about

implementing asthma-friendly policies

• Hosts data conferences to exchange current

information on asthma in Chicago, stimulate

newdatacolle

ctionactivitie

sandfindnew

ways of using data

Advocacy

Education

Collaboration

Chicago Asthma Consortium seeks to reduce

morbidity and mortality related to asthma

in the Chicago region through

advocacy, education and collaboration.

CAC is the only local organization dedicated solely to

improving the lives of those living with asthma in the

Chicago area and is one of the oldest and largest asthma

coalitions in the country. CAC brings together:

• Medical and public health professionals

• Business leaders

• Government agencies

• Community-based organizations

• Individuals dedicated to raising

awareness of asthma

Why get involved?

One in twelve people (about 25 million, or 8% of the U.S.

population) had asthma in 2009, and the number is

climbing. Chances are pretty good you know someone

whoisafflicte

d,perhapsev

enafamilym

emberor

someone close to you.

AtCAC,oneo

fourmoresig

nificantroles

istobean

advocate for asthma suffers and the communities that

support them. The moment you decide to get involved,

in whatever role you choose, you become an advocate

as well. Your continued support for those affected with

asthma or working in the asthma world is crucial to our

ongoing mission.

Connecting communities with resources.

CAC acts as the bridge that connects our community

partners with various health related research and

academic resources. CAC is led by its Board of Directors

andAdvisors

whoareexpe

rtsintheirfie

ldsandwell-

respected leaders in the Chicagoland asthma community.

Together, the Directors represent the CAC membership

and the professional asthma community, which includes

doctors and nurses from the top hospitals and clinics,

pharmacists, respiratory therapists, public health

professionals, educators, housing professionals,

government representatives, and community activists.

By bringing together and connecting key stakeholders

to both information and each other, CAC has been able to

identify and develop innovative programs to improve the

health of many Chicago residents with asthma.

chicagoasthma.org

Chicago Asthma Consortium

Stacy Ignoffo, MSW Executive Director

PO Box 31757, Chicago IL 60631 Phone: 888-268-8334 Fax: 773-628-7663

Direct Line: 773-628-7663

Email: [email protected] www.ChicagoAsthma.org

Enhancing Lives Through Advocacy, Education and Collaboration

Page 12: Lindsay Grace Portfolio

Connect with your colleagues any time, any where. Start a conversation, seek out hard-won wisdom and share comfortably in a member-only space.

Your community of colleagues is just a link away. http://connect.aoa.org

As an AOA member, you’re ALREADY a member of AOAConnect; just log in with your AOA email or member number to get started.

AOAConnect is mobile, just like you are. Download the mobile app by searching for “AOA” or “AOA Connect” in your device’s marketplace.

at home hereyou’re always

Connect with your colleagues any time, any where. Start a conversation, seek out hard-won wisdom and share comfortably in a member-only space.

Your community of colleagues is just a link away. http://connect.aoa.org

As an AOA member, you’re ALREADY a member of AOAConnect; just log in with your AOA email or member number to get started.

AOAConnect is mobile, just like you are. Download the mobile app by searching for “AOA” or “AOA Connect” in your device’s marketplace.

at home hereyou’re always

Connect with your colleagues any time, any where. Start a conversation, seek out hard-won wisdom and share comfortably in a member-only space.

Your community of colleagues is just a link away. http://connect.aoa.org

As an AOA member, you’re ALREADY a member of AOAConnect; just log in with your AOA email or member number to get started.

AOAConnect is mobile, just like you are. Download the mobile app by searching for “AOA” or “AOA Connect” in your device’s marketplace.

at home hereyou’re always

Project: AOA (American Optometric Association) ConnectGoal: Create a series of ads to announce the launch of a new online resource for doctors.

Jr. Sized Ad (Full pg, half pg and online ads were part of the project as well)

Page 13: Lindsay Grace Portfolio

Project: One Team One Goal Goal: Society of Gynecologic Oncology needed a logo and graphics to help brand a global project to “Join the Fight” against women’s cancer. The brand was translated into several different languages.

Online Graphics and Trade Show Sign

LogoButtons for Trade Show

Page 14: Lindsay Grace Portfolio

Xenografted Islet Cell Clusters From INSLEA29YTransgenic Pigs Rescue Diabetes and Prevent ImmuneRejection in Humanized MiceNikolai Klymiuk,1 Lelia van Buerck,2 Andrea Bähr,1 Monika Offers,2 Barbara Kessler,1

Annegret Wuensch,1 Mayuko Kurome,1 Michael Thormann,3 Katharina Lochner,2 Hiroshi Nagashima,4

Nadja Herbach,5 Rüdiger Wanke,5 Jochen Seissler,2 and Eckhard Wolf1

Islet transplantation is a potential treatment for type 1 diabetes,but the shortage of donor organs limits its routine application. Aspotential donor animals, we generated transgenic pigs expressingLEA29Y, a high-affinity variant of the T-cell costimulation inhibitorCTLA-4Ig, under the control of the porcine insulin gene promoter.Neonatal islet cell clusters (ICCs) from INSLEA29Y transgenic(LEA-tg) pigs and wild-type controls were transplanted intostreptozotocin-induced hyperglycemic NOD-scid IL2Rgnull mice.Cloned LEA-tg pigs are healthy and exhibit a strong b-cell–specifictransgene expression. LEA-tg ICCs displayed the same potential tonormalize glucose homeostasis as wild-type ICCs after transplan-tation. After adoptive transfer of human peripheral blood mononu-clear cells, transplanted LEA-tg ICCs were completely protectedfrom rejection, whereas reoccurrence of hyperglycemia was ob-served in 80% of mice transplanted with wild-type ICCs. In thecurrent study, we provide the first proof-of-principle report on trans-genic pigs with b-cell–specific expression of LEA29Y and their suc-cessful application as donors in a xenotransplantation model. Thisapproach may represent a major step toward the development of anovel strategy for pig-to-human islet transplantation without side ef-fects of systemic immunosuppression.Diabetes 61:1527–1532, 2012

Type 1 diabetes is a chronic metabolic disease as-sociated with development of severe complica-tions (1). It has been shown that type 1 diabetescan be cured by the transplantation of the pancreas

or isolated islets of Langerhans. Nonetheless, the success ofpancreas and islet transplantation is limited by the shortageof organ donors and the need for systemic immunosuppres-sive therapy (2) and is therefore restricted to few patients (3).

Limited availability of human donor organs may beovercome by the use of pigs as organ donors. Pig-to-human

xenotransplantation faces the problem of strong rejection,predominantly by direct T-cell recognition of pig majorhistocompatibility complex and indirect T-cell response toxenogeneic antigens presented by the recipient antigen-presenting cells (4).

Recent advances in immunosuppressive therapies pro-vided evidence that transplanted porcine islets can promotethe long-lasting cure of diabetes in nonhuman primates(5–7). However, the currently used intensive immunosup-pressive regimen in pig islet transplantation may have severeside effects in humans and cannot be transferred into clini-cal practice. Blockade of the B7/CD28 costimulatory path-way by LEA29Y, a high-affinity variant of the CTLA-4Igfusion protein (8), has been shown to be effective in clinicaltrials following kidney transplantation (9,10) and in porcineislet transplantation studies (5,7,11). Thus, local expressionof LEA29Y restricted to the transplantation site may repre-sent an innovative approach to protect grafted islets fromxenogeneic immune rejection without the side effects ofsystemic immunosuppression.

Therefore, we chose to generate transgenic pigs express-ing LEA29Y specifically in pancreatic b-cells. We demon-strate for the first time the potential of neonatal INSLEA29Ytransgenic (LEA-tg) islet clusters to normalize blood glucoselevels and evaluate the inhibition of human–anti-pig rejectionin a humanized NOD-scid IL2Rgnull (NSG) model.

RESEARCH DESIGN AND METHODSAll experiments were approved by the local animal welfare authority. NSG micewere obtained from The Jackson Laboratory. For generation of INSLEA-tg pigs,the coding sequence for LEA29Y was cloned into a b-cell–specific expressionvector (12) with 1.3-kb upstream regions, exon 1 and intron 1 of the porcineinsulin gene, and a poly-adenylation cassette of the bovine growth hormonegene. The vector was completed by linking the INSLEA construct to a floxedneomycin resistance cassette (13). Porcine fetal fibroblasts (PFF#14; 13 106)were nucleofected (Nucleofector Technology, Lonza, Germany). Stably nucle-ofected cell clones were used as donors for somatic cell nuclear transfer (14).Embryo transfer was carried out laparoscopically (15). Integration and ex-pression of the transgene was analyzed by Southern blot and immunohisto-chemistry. Donor piglets for transplantation experiments were generated byrecloning, as described previously (13).Isolation and transplantation of neonatal islet cell clusters intohyperglycemic NSG mice. Islet cell clusters (ICCs) from 1- to 2-day-oldrecloned LEA-tg and wild-type pigs were isolated as previously described (16)and cultured for 6 days at 37°C in RPMI (Biochrom) with 2% human serum al-bumin (Octapharm), 1% antibiotic-antimycotic, 10 mmol/L nicotinamide, and 20nmol/L exendine-4 (Sigma). Insulin content in ICCs was determined by enzyme-linked immunosorbent assay (ELISA) (Millipore) (17). A total of 2,500 clustersper mouse were transplanted under the kidney capsule of streptozotocin-induced diabetic (180 mg/kg; Sigma) NSG mice (blood glucose .350 mg/dL).Characterization of graft function. Neonatal ICCs require a 6- to 8-week invivo maturation period until physiological glucose-dependent insulin secretionhas developed. Animals with blood glucose levels .300 mg/dL received exog-enous insulin subcutaneously (0.5 IU glargine per day). Mice displaying blood

From the 1Chair for Molecular Animal Breeding and Biotechnology, and Lab-oratory for Functional Genome Analysis (LAFUGA), Gene Center, Ludwig-Maximilians-Universität, Munich, Germany; the 2Diabetes Zentrum,Medizinische Klinik Campus Innenstadt, Klinikum der Ludwig-Maximilians-Universität, Munich, Germany; the 3Department of Cardiac Surgery, Ludwig-Maximilians-Universität, Munich, Germany; the 4Laboratory of DevelopmentalEngineering, Meiji University, Kawasaki, Japan; and the 5Institute of VeterinaryPathology, Center for Clinical Veterinary Medicine, Ludwig-Maximilians-Universität, Munich, Germany.

Corresponding authors: Eckhard Wolf, [email protected], andJochen Seissler, [email protected].

Received 23 September 2011 and accepted 28 January 2012.DOI: 10.2337/db11-1325This article contains Supplementary Data online at http://diabetes

.diabetesjournals.org/lookup/suppl/doi:10.2337/db11-1325/-/DC1.N.K., L.v.B., J.S., and E.W. contributed equally to this work.� 2012 by the American Diabetes Association. Readers may use this article as

long as the work is properly cited, the use is educational and not for profit,and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

See accompanying commentary, p. 1348.

diabetes.diabetesjournals.org DIABETES, VOL. 61, JUNE 2012 1527

BRIEF REPORT

Diabetes Volume 61, May 2012ORIGINAL ARTICLE1160

Prevention of Type 1 Diabetes in the Rat With an Allele-Specific Anti–T-Cell Receptor Antibody:Vß13 as a Therapeutic Target and Biomaker

From the 1Department of Medicine, University of Massachusetts Medical School, Worcester, MA; the 2Department of Microbiology and Immunology, Center for Immunogenetics and Inflammatory Diseases, Drexel University College of Medicine, Philadelphia, PA; the 3Institute for Virology and Immunobiology, University of Würzburg, Würzburg, Germany; the 4Department of Molecular Medicine, University of Massachusetts Medical School, Worcester, MA; the 5Division of Research Development, Biomedical Research Models, Inc., Worcester, MA.

Corresponding author: John P. Mordes, [email protected]

Received 25 August 2011 and accepted 14 December 2011.

Z.L. is currently affiliated with the Department of Medical Microbiology, Weifang Medical University, Shandong, China.

The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health.

© 2012 by the American Diabetes Association. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

See accompanying commentary, p. 976.

Zhijun Liu,1 Laura Cort,2 Ryan Eberwine,2 Thomas Herrmann,3 Jean H. Leif,4 Dale L. Greiner,4 Barak Yahalom,5

Elizabeth P. Blankenhorn,2 and John P. Mordes1

In earlier studies of the Iddm14 diabetes susceptibility locus in the rat, we identified an allele of the T cell receptor (TCR) beta chain, Tcrb-V13S1A1, as a candidate gene. To establish its importance, we treated susceptible rats with a depleting anti-rat Vß13 monoclonal antibody and then exposed them to either polyinosinic:polycytidylic acid or a diabetogenic virus to induce diabetes. The overall frequency of diabetes in controls was 74% (N=50) compared with 17% (N=30) in anti-Vß13 treated animals, with minimal islet pathology in non-diabetic treated animals. T cells isolated from islets on day 5 after starting induction showed a greater proportion of Vß13+ T cells than did peripheral lymph node T cells. Vß13 transcripts recovered from day 5 islets revealed focused Jß usage and less CDR3 diversity than did transcripts from peripheral Vß13+ T cells. CDR3 usage was not skewed in control Vß16 CDR3 transcripts. Anti-rat Vß13 antibody also prevented spontaneous diabetes

in BBDP rats. The Iddm14 gene is likely to be Tcrb-V13, indicating that TCR beta chain usage is a determinant of susceptibility to autoimmune diabetes in rats. It may be possible to prevent autoimmune diabetes by targeting a limited element of the T cell repertoire. Diabetes 61:1160–1168, 2012 | DOI: 10.2337/db11-0867

Type 1 diabetes is a T cell-mediated autoimmune disorder, the fundamental cause of which is unknown (1). Most strategies to prevent, arrest, or reverse it target T cells, either directly by altering number or function, or indirectly via tolerizing antigens. To date, some interventions appear to preserve some beta cells after onset (2,3), but none safely and effectively prevent or reverse the disease.

A major need is for new disease-specific modalities that avoid broad spectrum targeting of immune system components. This is difficult because multiple antigenic specificities participate in the diabetogenic response, and multiple alleles of immune system genes contribute

META

BOLIS

M

Project: ADA(American Diabetes Association) Diabetes JournalGoal: Interior layout refresh. Create a new layout, templates/guidelines to match the recently updated cover.

Article AfterBefore

Cover (Just for example)

Page 15: Lindsay Grace Portfolio

Genetic Predictors ofWeight Loss andWeight Regain After Intensive LifestyleModification, Metformin Treatment,or Standard Care in the DiabetesPrevention ProgramLINDA M. DELAHANTY, MS, RD

1,2

QING PAN, PHD3

KATHLEEN A. JABLONSKI, PHD3

KAROL E. WATSON, MD, PHD4

JEANNE M. MCCAFFERY, PHD5

ALAN SHULDINER, MD6

STEVEN E. KAHN, MB, CHB7

WILLIAM C. KNOWLER, MD, DRPH8

JOSE C. FLOREZ, MD, PHD1,2,9,10

PAUL W. FRANKS, PHD, MPHIL, MS11,12

FOR THE DIABETES PREVENTION PROGRAMRESEARCH GROUP*

OBJECTIVEdWe tested genetic associations with weight loss and weight regain in the Di-abetes Prevention Program, a randomized controlled trial of weight loss–inducing interventions(lifestyle and metformin) versus placebo.

RESEARCHDESIGNANDMETHODSdSixteen obesity-predisposing single nucleotidepolymorphisms (SNPs) were tested for association with short-term (baseline to 6 months) andlong-term (baseline to 2 years) weight loss and weight regain (6 months to study end).

RESULTSdIrrespective of treatment, theAla12 allele atPPARG associatedwith short- and long-termweight loss (20.63 and 20.93 kg/allele, P# 0.005, respectively). Gene–treatment interactions wereobserved for short-term (LYPLAL1 rs2605100, Plifestyle*SNP = 0.032;GNPDA2 rs10938397, Plifestyle*SNP =0.016; MTCH2 rs10838738, Plifestyle*SNP = 0.022) and long-term (NEGR1 rs2815752, Pmetformin*SNP =0.028; FTO rs9939609, Plifestyle*SNP = 0.044) weight loss. Three of 16 SNPs were associated with weightregain (NEGR1 rs2815752, BDNF rs6265, PPARG rs1801282), irrespective of treatment. TMEM18rs6548238 and KTCD15 rs29941 showed treatment-specific effects (Plifestyle*SNP , 0.05).

CONCLUSIONSdGenetic information may help identify people who require additionalsupport to maintain reduced weight after clinical intervention.

Diabetes Care 35:363–366, 2012

Multiple obesity-predisposing genevariants are known (1,2), whichmay interact with lifestyle tomod-

ify obesity risk (3). It is unknownwhetherthese variants influence weight regain(WR) after intentional weight loss (WL).We therefore tested associations of 16obesity-predisposing variants with weightchange in Diabetes Prevention Program(DPP) participants.

RESEARCH DESIGN ANDMETHODSdThe DPP is describedelsewhere (4,5). In brief, 3,234 over-weight/obese adults with impaired glu-cose tolerance were randomly assignedto placebo, 850 mg metformin twicedaily, or intensive lifestyle modificationaimed at ;150 min of physical activityper week and ;7% WL, to compare ef-fects on diabetes incidence. Participantsprovided written informed consent, andinstitutional review boards of 27 DPPstudy centers approved the study.

ParticipantsOf 3,597 participants with baseline and1-year data available, 93.3% consented togenetic analyses. Of these, 56.1%were non-Hispanicwhite (NHW), 20.4%wereAfricanAmerican, 16.7%wereHispanic, 4.4%wereAsian American, and 2.5% were AmericanIndian; on average participants weremiddle-aged and obese (see Supplemen-tary Table 1 for participant characteristics).

GenotypingSixteen obesity-predisposing variants re-ported elsewhere (1,2) or in the DPP (6)were genotyped as described previously(6); genotyping success rates exceeded99% (Supplementary Table 2).

Statistical analysisAnalyses were performed using SAS v9.2(Cary, NC). Predictor variables were singlenucleotide polymorphisms (SNPs), witheffect alleles coded consistent with the as-sociation of each SNP with BMI or waistcircumference in published meta-analyses

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From the 1Diabetes Research Center, Massachusetts General Hospital, Boston, Massachusetts; the 2Department ofMedicine, Harvard Medical School, Boston, Massachusetts; 3The Biostatistics Center, George Washington Uni-versity, Rockville, Maryland; the 4David Geffen School of Medicine, University of California at LosAngeles, Los Angeles, California; the 5Weight Control and Diabetes Research Center, The Miriam Hospital andBrown Medical School, Providence, Rhode Island; the 6Division of Endocrinology, Diabetes and Nutrition,Department of Medicine, and Program in Genetics and Genomic Medicine, University of Maryland School ofMedicine, Baltimore, Maryland; the 7Division of Metabolism, Endocrinology and Nutrition, Department ofMedicine, VAPuget SoundHealthCare SystemandUniversity ofWashington, Seattle,Washington; the 8NationalInstitute of Diabetes and Digestive and Kidney Diseases, Phoenix, Arizona; the 9Center for Human Genetic Re-search, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts; the 10Program inMedical and Population Genetics, Broad Institute, Cambridge, Massachusetts; the 11Department of ClinicalSciences,Genetic andMolecular EpidemiologyUnit, LundUniversityDiabetesCenter, SkåneUniversityHospital,Malmö, Sweden; and the 12Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts.

Corresponding author: Paul W. Franks, [email protected] and [email protected] 25 July 2011 and accepted 23 October 2011.DOI: 10.2337/dc11-1328. Clinical trial reg. no. NCT00004992, clinicaltrials.gov.This article contains Supplementary Data online at http://care.diabetesjournals.org/lookup/suppl/doi:10

.2337/dc11-1328/-/DC1.*A complete list of centers, investigators, staff, additional methods, results, and list of Diabetes Prevention

Program Research Group investigators (Genetics version) can be found in the Supplementary Data online.The opinions expressed are those of the investigators and do not necessarily reflect the views of the Indian

Health Service or other funding agencies.© 2012 by the American Diabetes Association. Readers may use this article as long as the work is properly

cited, the use is educational and not for profit, and thework is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

care.diabetesjournals.org DIABETES CARE, VOLUME 35, FEBRUARY 2012 363

P a t h o p h y s i o l o g y / C o m p l i c a t i o n sB R I E F R E P O R T

Diabetes Care Volume 35, February 2012204 ORIGINAL ARTICLE

A Randomized Clinical Trial to Assess the Efficacy and Safety of Real-Time Continuous Glucose Monitoring in the Management of Type 1 Diabetes in Young Children Aged 4 to < 10 Years

From the 1Nemours Children’s Clinic, Pediatric Endocrinology, Jacksonville, FL US; 2Jaeb Center for Health Research, Tampa, FL, US; 3Stanford University, Pediatric Endocrinology, Stanford, CA, US; 4University of Iowa, Pediatric Endocrinology, Iowa City, IA, US; 5Washington University, Department of Pediatrics, St. Louis, MO, US; 6Yale University, Pediatric Endocrinology, New Haven, CT, US.Corresponding author: Nelly Mauras, [email protected] 8 September 2011 and accepted 30 October 2011.Clinical trial reg. no. NCT00760526, clinicaltrials.gov.* A complete list of members of the DirecNet Study Group can be found in the Appendix

The contents of this article are solely the responsibility of the authors and do not necessarily represent the official view of the National Center for Research Resources or the National Institutes of Health.© 2012 by the American Diabetes Association.

See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

Nelly Mauras,1 Roy Beck,2 Dongyuan Xing,2 Katrina Ruedy,2 Bruce Buckingham,3 Michael Tansey,4 Neil H. White,5 Stuart A. Weinzimer,6 William Tamborlane,6 Craig Kollman,2

and The Diatbetes Research in Children Network (DirecNet) Study Group*

OBJECTIVE

Continuous glucose monitoring (CGM) has been demonstrated to improve glycemic control in adults with type 1 diabetes (T1D), but less so in children. We designed a study to assess CGM benefit in young children 4 to 9 years with T1D.

RESEARCH DESIGN AND METHODS

Following a run-in phase, 146 children with T1D (mean age: 7.5 ± 1.7 years, 64% on pumps, median diabetes duration 3.5 years) were randomly assigned to CGM or to usual care. The primary outcome was reduction in HbA1c at 26 weeks by ≥0.5% without the occurrence of severe hypoglycemia.

RESULTS

The primary outcome was achieved by 19% in the CGM group and 28% in the control group (P=0.17). Mean change in HbA1c was −0.1% in each group (P=0.79). Severe hypoglycemia rates were similarly low in both groups. CGM wear decreased over time, with only 41% averaging at least 6 days/week at 26 weeks. There was no correlation between CGM use and change in HbA1c (r =−0.09, P=0.44). CGM wear was well tolerated and parental satisfaction with CGM was high. However, parental fear of hypoglycemia was not reduced.

CONCLUSIONS

CGM in 4 to 9 year olds did not improve glycemic control despite a high degree of parental satisfaction with CGM. We postulate that this finding may be related in part to limited use of the CGM glucose data in day-to-day management and to an unremitting fear of hypoglycemia. Overcoming the barriers that prevent integration of these critical glucose data into day-to-day management remains a challenge. Diabetes Care 35:204–210,2012 | DOI: 10.2337/dc11-1746.

Continuous glucose monitoring (CGM) has made it possible to assess the patterns and trends of blood glucose and the substantial variability in glucose excursions in people with type 1 diabetes, even in those who are well controlled (1). The benefits of this technology are most apparent with near-continuous wear of the sensors in which knowledge gained in identifying glycemic patterns, such as with

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