Lindsay Grace Portfolio by Lindsay Grace

lindsaygrace Portfolio 2014

ADDY award winner 2009

BROOKFIELD ZOO Welcomes You to the GRAND OPENING of the

BUTTERFLY EXHIBITION MARK YOUR CALENDARS

May 20th 2010 at 10:00am

DLEIFKOORB

OOZ

and come celebrate with us at our ribbon cutting ceremony.

:stneserP

BROOKFIELD

ZOO

Located on First Avenue in Brookfield Illinois For more information contact us at our guest line (708) 688-8000 or visit us at our website

Presents:

www.brookfieldzoo.org

Invitation

Project: Brookfield Zoo Invitation Goal: Conceptualize an original event then

create an invitation and thank you card. Artwork was hand-drawn and then made digital.

Thank You Card

Project: BFA Senior Capstone Gallery Show Goal: The poster and postcard used to

G F O N G VI

promote the actual exhibition of senior BFA students capstone and portfolio pieces. Showcasing my photography and photo manipulation.

one t s a p A rt s C i o ra p h i c h ow n e S Gr lio S A & tfo F B Po r

N I O M OW SH

BFA Senior CApStone & GrAphiC ArtS 2012 portFolio Show A capstone exhibition featuring graduating seniors in the School of Design and Fashion

Davis Art Gallery Stephens College

April 6 – May 4 Admission is Free

M – F: 10 – 3 (or by appt)

2 1 0

MoVinG on & ShowinG oFF

Postcard: Front

BFA Senior Capstone capstone exhibition featuring graduating & Graphic Arts Aseniors in the School of Design and Fashion 2012 Portfolio Show Davis Art Gallery Stephens College

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

April 6 – May 4

Admission is Free M – F: 10 – 3

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

Gallery located Corner of Walnut & Ripley Email Dan Scott at dscott@stephens.edu for Info Gallery located Corner of Walnut & Ripley. Email Dan Scott at dscott@stephens.edu for Info

Postcard: Back

& N O F

Poster

Art in the Park Experience the Magic

Stephens Lake Park June 5th – 6th, 2010

Sat 10am–5pm | Sun 10am–4pm

Art in the Park Experience the Magic

T-Shirt

June 5th –6th, 2010

Sat 10am–5pm | Sun 10am–4pm

Project: Art in the Park Goal: Design an advertising campaign for Columbia, Missouri’s annual summer art festival. Runner up. Art work is hand drawn and then was made digital. For a complete list of artists and performance schedules visit artinthepark.missouri.org or call Columbia Art League at 573-443-8838

Poster

Program

Project: Hands for Hope Goal: 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.

HANDS f or HOPE T-Shirt

HANDS for HOPE

HANDS for HOPE HOME

ABOUT US

PROGRAMS

EVENTS

RESOURCES

CONTACT

EVENTS

Grand Opening: June 8 Opening Ceremony and Ribbon-Cutting at 6:30 pm live music, appetizers and refreshments to follow silent auction and raffle at 8 pm

TORN: June 25-July14 Opening 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

Website

(773) 367-4673

Banner

Poster

Harbinger

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

Harbinger 2012

Speer Morgan, Editor The Missouri Review

First place winner in the 2009, 2010 and 2011 Literary Arts Journal category. Sigma Tau Delta International English Honors Society

Stephens College

“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, Editor Typecast Publishing

“Imaginatively designed and packed with superb writing, Harbinger is always a pleasure to behold.” Andrew Leland, Editor the Believer

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

ll d is

2 012

Gabriel Fried, Poetry Editor Persea Books

c l o su

Clawson

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

Interior Spread

“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

Non-Fiction

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.

61 Clawson

Non-Fiction

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.

Project: Harbinger Literary Magazine Goal: 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

THE STEPHENS COLLEGE PLAYHOUSE THEATRE COMPANY PRESENTS

THE

Website Banner

THE STEPHENS COLLEGE PLAYHOUSE THEATRE COMPANY PRESENTS

HOUSE OF BLUE LEAVES By John Guare

THE

HOUSE OF BLUE LEAVES By John Guare

Oct. 28-29 Nov. 4-5 7:30 p.m. Oct. 30 2 p.m. Sunday Matinee $14 General $7 Student/Senior

OCTOBER 28-30, NOVEMBER 4-5

Friâ&#x20AC;&#x201C;Sat 7:30 p.m. | Sun Matinee at 2 p.m.

Project: The House of Blue Leaves Goal: Manage the ad campaign for

Stephens College School of Performing Arts show for my internship. Half painted, half manipulated image in Photoshop.

Macklanburg Playhouse 100 Willis Ave.

Stephens College Box Office

General $14 Student/Senior $7 Macklanburg Playhouse 100 Willis Ave.

Stephens College Box Office

(573) 876-7199 boxoffice@stephens.edu www.stephens.edu/performingarts

Newspaper Ad

Special Thanks to Our Performance Sponsor:

Watkins Roofing

And Season Sponsors: KFRU News Talk 1400 AM & Joe Machens Dealerships

(573) 876-7199 boxoffice@stephens.edu www.stephens.edu/performingarts 5464

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

Poster

THE STEPHENS COLLEGE PLAYHOUSE THEATRE COMPANY PRESENTS

Newspaper Ad

CIRCLE

MIRROR

TRANSFORMATION

TRANS-

BY ANNIE BAKER SEPT. 23-25, SEPT. 30-OCT. 1 Fri–Sat 7:30 p.m. | Sun Matinee at 2 p.m. Macklanburg Playhouse 100 Willis Ave.

General $14 Student/Senior $7

Stephens College Box Office

FORMATION

(573) 876-7199 boxoffice@stephens.edu

$2 OFF ANY TICKET FOR ANY PERFORMANCE

(Mention “Columbia Welcomes You” at the Box Office)

Special Thanks to Our Performance Sponsor: McDonald’s

And Season Sponsors: KFRU News Talk 1400 AM & Joe Machens Dealerships 5463

WWW.STEPHENS.EDU/PERFORMINGARTS

BY ANNIE BAKER Sept. 23-24 Sept. 30-Oct. 1 7:30 p.m. Sept. 25 2 p.m. Sunday Matinee Stephens College Box Office

$14 General $7 Student/Senior Macklanburg Playhouse 100 Willis Ave.

(573) 876-7199 boxoffice@stephens.edu www.stephens.edu/performingarts 5464

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

Poster

Website Banner

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

Art + Science

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

A new perspective on medical design.

p 847.844.8640 F 847.844.8670

www.RxCreativeLab.com

Focused, holistic communications for medical associations. www.RxCreativeLab.com

Direct Mail

Website

Focuse

d, holis tic com munica for me dical a tions ssociati ons.

Lindsa yG

race Gr ap hi c De si gn er t M ain St re et , Su Wes t D un de e, ite 10 1 IL 60 11 8 P 84 7.8 44 .8 64 0 F 84 7. 84 4. 86 Lindsa 70 y@RxCr ea tiveL w w w.R ab .com xC re at iveL ab .com 89 Wes

Letterhead

Project: RxCreativeLab Re Branding Goal: Design a new logo and brand based on

the repositioning of the company to focus on designing for medical associations. Logo (Backgrounds and text colors change)

Business Cards

Get Involved. Stay Involved.

Letterhead

Membership in the CAC is open to individuals and organizations active in and seeking to improve the quality of life for people with asthma.

Mission

Enhancing Lives Through Advocacy, Education and Collaboration

The Chicago Asthma Consortium is a coalition of medical

Your continued support is what allows us to strengthen

and public health professionals, business leaders,

our efforts to engage the asthma community, build

government agencies, community-based organizations,

stronger partnerships with key research and academic

and individuals dedicated to improving the quality of life

resources, educate and collaborate with our many

for people with asthma through networking, information

stakeholders, and ultimately better the lives of those

sharing, education, and collaboration.

afflicted with asthma.

Purpose

Once you become a member, you can receive:

The Chicago Asthma Consortium brings together the

Enhancing Lives Through Advocacy, Education and Collaboration

Chicagoans living with asthma.

• The opportunity to participate in Chicago’s only group of asthma advocates

Goals

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

asthma community to improve the quality of life for

•

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

ation Educ

education programs.

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• 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

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munity r com ts ou and nnec at co ors search ge th Direct ed re e brid the community to appropriately diagnose and better ard of h relat as th healt its Bo elln.our website at www.ChicagoAsthma.org acts Simply visit tio rious led by CAC a and w va . manage asthma. is lds th uc C fie CA munity ers wi a edand get involved today! in their a com urces. hm partn ts m st so er th a y re as xp rshipBox 31757, Chicago IL 60631 • Encourage asthma patients, regardless of income,rt in r ke PO emic land are e embe acad arm ou icago s who C mPhone: es e effo is to e Ch 888-268-8334 Fax: 773-628-7663 color, gender, creed, language or disability, visor e CA includ s in th ing th to enter e with asthma rses, pharmaent th ich er and Ad d es ad a wh pr , Le access to care. ity s,www.ChicagoAsthma.org into continuing care by facilitating nu s re ted le nals, lp thos mmun rector essio d clinic ctors, respec ls an ma co y to he the Di h prof rea do spita l asth ther, nal go -a h her wa c healt Toge siona top ho Anot ucatio publi , Chica c healt ists, profes m the publi uch ed olders ls, mplish d the ists, es fro therap as m rs na co an ap ry stakeh th nu er ac to sio th To rs, wi ists. s and profes respira ible. iratory embe activ doctor poss using cists, ity m s, resp unity s as s, ho acist mmun comm ogram ucator g pharm olders , and and co ls, ed orkin and pr to tatives stakeh netw siona ation able g key e l and presen profes inform -edg ectin s been ationa ent re C ha educ cutting d conn CAC: vernm e the al CA an on go r, on this, n er pr im ov regi othe matio togeth ents ms to d each e infor inging Implem progra a. ion an re provid By br • ormat asthm gs to ovative ma ca inf ch th th tin inn ar wi th as ee p m lo to ents to bo g rese deve resid related ergin y and arch icago topics on em rese identif ions any Ch ns in cuss h of m irectio s dis d to healt d ture d Lead y Boar to • ncerne visor and fu solely rs co dings ity Ad ated d othe fin mmun dic e an de th Co s a er a in ation a enes caregiv asthm Conv organiz asthm with tients, • local gest ge pa t e living only and lar enga s abou is the of thos dest ma giver CAC the ol ther: e lives t asth d care ies abou ing th s toge one of polic ols an bring improv and is scho friendly es . CAC area arrent ls at try m go ge cu siona Educ coun Chica g asth chan • profes in the ex entin h ulate to ns em alt s tio impl , stim c he ence coali publi icago confer new l and a in Ch s data find Medica asthm Host s and s on • er itie n • ad atio activ ess le ction inform le s Busin ol cie ta c • t agen w da ta ations nmen ne ing da Gover of us organiz • ways -based ng munity to raisi Com ated • dedic a iduals m th Indiv s of as • enes awar U.S. d? of the volve , or 8% is get in million mber ut 25 Why the nu le (abo meone , and peop ow so 20 09 elve you kn ma in r in tw th e od r o ce as go On had embe pret ty to redu ily m lation) s are a fam seeks asthma popu ance even rtium g. Ch to erhaps Conso y related climbin ted, p be an hma ugh lit is to st u. ro ta A is af flic es yo at n. th o ol or go t r m wh s th se to gion llaboratio fican unitie Chica dity and ne clo signi go re co comm ved, someo more d the morbi the Chica ion and t invol of our rs an in te e to ge , one ucat a suffe voca decid At CAC cy, ed an ad asthm t you r e ca fo en m th vo wi cate ad e mom u beco fected advo se, yo r em. Th ose af to ou or t th u choo t for th supp crucial role yo ppor rld is ed su atever a wo ntinu in wh asthm ur co ll. Yo in the as we rking wo a or n. asthm issio ing m ongo •

Facilitate a collaboration among healthcare

professionals to identify resources available in

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Brochure

Chicago Asthma Consortium Enhancing Lives Through Advocacy, Education and Collaboration

chicagoasthma.org 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: stacychgoasthma@gmail.com www.ChicagoAsthma.org

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Business Cards

Phone: 888.268.8334

•

Fax: 773.628.7663

•

www.ChicagoAsthma.org

Project: Chicago Asthma Consortium Goal: Design a new brand for a chicago-based

non-for-profit. Develop a logo and carry a brand theme through multiple design pieces.

you’re always at here

home

you’re always at here

home

you’re always at here

home

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

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

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

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

Buttons for Trade Show

Logo

Online Graphics and Trade Show Sign

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.

1160

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

Cover (Just for example)

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

Project: ADA(American Diabetes Association)

Diabetes Journal

Goal: Interior layout refresh. Create a new

layout, templates/guidelines to match the recently updated cover.

METABOLISM

BRIEF REPORT

Xenografted Islet Cell Clusters From INSLEA29Y Transgenic Pigs Rescue Diabetes and Prevent Immune Rejection in Humanized Mice Nikolai 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. As potential donor animals, we generated transgenic pigs expressing LEA29Y, a high-affinity variant of the T-cell costimulation inhibitor CTLA-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 into streptozotocin-induced hyperglycemic NOD-scid IL2Rgnull mice. Cloned LEA-tg pigs are healthy and exhibit a strong b-cell–specific transgene expression. LEA-tg ICCs displayed the same potential to normalize glucose homeostasis as wild-type ICCs after transplantation. After adoptive transfer of human peripheral blood mononuclear cells, transplanted LEA-tg ICCs were completely protected from rejection, whereas reoccurrence of hyperglycemia was observed in 80% of mice transplanted with wild-type ICCs. In the current study, we provide the first proof-of-principle report on transgenic pigs with b-cell–specific expression of LEA29Y and their successful application as donors in a xenotransplantation model. This approach may represent a major step toward the development of a novel strategy for pig-to-human islet transplantation without side effects of systemic immunosuppression. Diabetes 61:1527–1532, 2012

ype 1 diabetes is a chronic metabolic disease associated with development of severe complications (1). It has been shown that type 1 diabetes can be cured by the transplantation of the pancreas or isolated islets of Langerhans. Nonetheless, the success of pancreas and islet transplantation is limited by the shortage of organ donors and the need for systemic immunosuppressive therapy (2) and is therefore restricted to few patients (3). Limited availability of human donor organs may be overcome by the use of pigs as organ donors. Pig-to-human 1

From the Chair for Molecular Animal Breeding and Biotechnology, and Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, LudwigMaximilians-Universität, Munich, Germany; the 2 Diabetes Zentrum, Medizinische Klinik Campus Innenstadt, Klinikum der Ludwig-MaximiliansUniversität, Munich, Germany; the 3Department of Cardiac Surgery, LudwigMaximilians-Universität, Munich, Germany; the 4Laboratory of Developmental Engineering, Meiji University, Kawasaki, Japan; and the 5Institute of Veterinary Pathology, Center for Clinical Veterinary Medicine, Ludwig-MaximiliansUniversität, Munich, Germany. Corresponding authors: Eckhard Wolf, ewolf@lmb.uni-muenchen.de, and Jochen Seissler, jochen.seissler@med.uni-muenchen.de. Received 23 September 2011 and accepted 28 January 2012. DOI: 10.2337/db11-1325 This 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

Before

Diabetes Volume 61, May 2012

ORIGINAL ARTICLE

xenotransplantation faces the problem of strong rejection, predominantly by direct T-cell recognition of pig major histocompatibility complex and indirect T-cell response to xenogeneic antigens presented by the recipient antigenpresenting cells (4). Recent advances in immunosuppressive therapies provided evidence that transplanted porcine islets can promote the long-lasting cure of diabetes in nonhuman primates (5–7). However, the currently used intensive immunosuppressive regimen in pig islet transplantation may have severe side effects in humans and cannot be transferred into clinical practice. Blockade of the B7/CD28 costimulatory pathway by LEA29Y, a high-affinity variant of the CTLA-4Ig fusion protein (8), has been shown to be effective in clinical trials following kidney transplantation (9,10) and in porcine islet transplantation studies (5,7,11). Thus, local expression of LEA29Y restricted to the transplantation site may represent an innovative approach to protect grafted islets from xenogeneic immune rejection without the side effects of systemic immunosuppression. Therefore, we chose to generate transgenic pigs expressing LEA29Y specifically in pancreatic b-cells. We demonstrate for the first time the potential of neonatal INSLEA29Y transgenic (LEA-tg) islet clusters to normalize blood glucose levels and evaluate the inhibition of human–anti-pig rejection in a humanized NOD-scid IL2Rgnull (NSG) model.

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

RESEARCH DESIGN AND METHODS All experiments were approved by the local animal welfare authority. NSG mice were obtained from The Jackson Laboratory. For generation of INSLEA-tg pigs, the coding sequence for LEA29Y was cloned into a b-cell–specific expression vector (12) with 1.3-kb upstream regions, exon 1 and intron 1 of the porcine insulin gene, and a poly-adenylation cassette of the bovine growth hormone gene. The vector was completed by linking the INSLEA construct to a floxed neomycin resistance cassette (13). Porcine fetal fibroblasts (PFF#14; 13 106) were nucleofected (Nucleofector Technology, Lonza, Germany). Stably nucleofected cell clones were used as donors for somatic cell nuclear transfer (14). Embryo transfer was carried out laparoscopically (15). Integration and expression of the transgene was analyzed by Southern blot and immunohistochemistry. Donor piglets for transplantation experiments were generated by recloning, as described previously (13). Isolation and transplantation of neonatal islet cell clusters into hyperglycemic NSG mice. Islet cell clusters (ICCs) from 1- to 2-day-old recloned 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 albumin (Octapharm), 1% antibiotic-antimycotic, 10 mmol/L nicotinamide, and 20 nmol/L exendine-4 (Sigma). Insulin content in ICCs was determined by enzymelinked immunosorbent assay (ELISA) (Millipore) (17). A total of 2,500 clusters per mouse were transplanted under the kidney capsule of streptozotocininduced diabetic (180 mg/kg; Sigma) NSG mice (blood glucose .350 mg/dL). Characterization of graft function. Neonatal ICCs require a 6- to 8-week in vivo maturation period until physiological glucose-dependent insulin secretion has developed. Animals with blood glucose levels .300 mg/dL received exogenous insulin subcutaneously (0.5 IU glargine per day). Mice displaying blood DIABETES, VOL. 61, JUNE 2012

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, john.mordes@umassmed.edu

1527

Article After

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.

204

ORIGINAL ARTICLE

Diabetes Care Volume 35, February 2012

CLIN CARE/EDUCATION/NUTRITION/PSYCHOSOCIAL

Cover (Just for example)

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

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*

Project: ADA(American Diabetes Association)

layout, templates/guidelines to match the recently updated cover.

OBJECTIVE

Pathophysiology/Complications B R I E F

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. 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.

LINDA M. DELAHANTY, MS, RD1,2 QING PAN, PHD3 KATHLEEN A. JABLONSKI, PHD3 KAROL E. WATSON, MD, PHD4 JEANNE M. MCCAFFERY, PHD5 ALAN SHULDINER, MD6

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.

From the 1Nemours Children’s Clinic, Pediatric Endocrinology, Jacksonville, FL US; 2Jaeb Center for Health Research, Tampa, FL, US; 3 Stanford 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.

CONCLUSIONS

Corresponding author: Nelly Mauras, direcnet@jaeb.org.

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

R E P O R T

Genetic Predictors of Weight Loss and Weight Regain After Intensive Lifestyle Modiﬁcation, Metformin Treatment, or Standard Care in the Diabetes Prevention Program

RESEARCH DESIGN AND METHODS

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.

Received 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.

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 PROGRAM RESEARCH GROUP*

OBJECTIVEdWe tested genetic associations with weight loss and weight regain in the Diabetes Prevention Program, a randomized controlled trial of weight loss–inducing interventions (lifestyle and metformin) versus placebo. RESEARCH DESIGN AND METHODSdSixteen obesity-predisposing single nucleotide polymorphisms (SNPs) were tested for association with short-term (baseline to 6 months) and long-term (baseline to 2 years) weight loss and weight regain (6 months to study end). RESULTSdIrrespective of treatment, the Ala12 allele at PPARG associated with short- and long-term weight loss (20.63 and 20.93 kg/allele, P # 0.005, respectively). Gene–treatment interactions were observed 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 weight regain (NEGR1 rs2815752, BDNF rs6265, PPARG rs1801282), irrespective of treatment. TMEM18 rs6548238 and KTCD15 rs29941 showed treatment-speciﬁc effects (Plifestyle*SNP , 0.05). CONCLUSIONSdGenetic information may help identify people who require additional support to maintain reduced weight after clinical intervention. Diabetes Care 35:363–366, 2012

c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c 1

From the Diabetes Research Center, Massachusetts General Hospital, Boston, Massachusetts; the Department of Medicine, Harvard Medical School, Boston, Massachusetts; 3The Biostatistics Center, George Washington University, Rockville, Maryland; the 4David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California; the 5Weight Control and Diabetes Research Center, The Miriam Hospital and Brown 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 of Medicine, Baltimore, Maryland; the 7Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, VA Puget Sound Health Care System and University of Washington, Seattle, Washington; the 8National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, Arizona; the 9Center for Human Genetic Research, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts; the 10Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts; the 11Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University Diabetes Center, Skåne University Hospital, Malmö, Sweden; and the 12Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts. Corresponding author: Paul W. Franks, paul.franks@med.lu.se and dppmail@biostat.bsc.gwu.edu. Received 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 the work is not altered. See http://creativecommons.org/ licenses/by-nc-nd/3.0/ for details.

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ultiple obesity-predisposing gene variants are known (1,2), which may interact with lifestyle to modify obesity risk (3). It is unknown whether these variants inﬂuence weight regain (WR) after intentional weight loss (WL). We therefore tested associations of 16 obesity-predisposing variants with weight change in Diabetes Prevention Program (DPP) participants. RESEARCH DESIGN AND METHODSdThe DPP is described elsewhere (4,5). In brief, 3,234 overweight/obese adults with impaired glucose tolerance were randomly assigned to placebo, 850 mg metformin twice daily, or intensive lifestyle modiﬁcation aimed at ;150 min of physical activity per week and ;7% WL, to compare effects on diabetes incidence. Participants provided written informed consent, and institutional review boards of 27 DPP study centers approved the study. Participants Of 3,597 participants with baseline and 1-year data available, 93.3% consented to genetic analyses. Of these, 56.1% were nonHispanic white (NHW), 20.4% were African American, 16.7% were Hispanic, 4.4% were Asian American, and 2.5% were American Indian; on average participants were middle-aged and obese (see Supplementary Table 1 for participant characteristics). Genotyping Sixteen obesity-predisposing variants reported elsewhere (1,2) or in the DPP (6) were genotyped as described previously (6); genotyping success rates exceeded 99% (Supplementary Table 2). Statistical analysis Analyses were performed using SAS v9.2 (Cary, NC). Predictor variables were single nucleotide polymorphisms (SNPs), with effect alleles coded consistent with the association of each SNP with BMI or waist circumference in published meta-analyses

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