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If you're a newcomer reasoning of connexion an associate system or purchase an online product, you'll locate that find the authority one is beautiful some close to purchasing for cereal! Every bundle is professionally planned to invasion your renown. Every wares claims to be the longest. Everyone claims to be THE mercantilism 'guru' who can make plain you the way to straightforward possessions. You solely status to portent on the stippled queue (or enter upon your gratitude card numeral) and you're on your way to casual way.
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Savannah Fox – Slutty Savannah
Released: February 28, 2014
Wanna spend some alone time with Savannah Fox in her bed? Of course you do, that's a given. Savannah Fox is a porn starlet that was built to use her hands and and filthy talk to get your cock nice and stiff. Your fun with Savannah begins with her fucking herself silly with a glass dildo. Act 2 gets going when she turns her attention to the bulge in your pants, and, well, that's when things really get going. Spend some bedroom time with Savannah Fox and your balls will thank you for it.

subset: commoncrawl


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So my scans are abit wonky but I reallllly wanted to share these pics of super star stylist (wife. mum AND international pilot!) LeeAnn Yare's home! I got my "Your Home and Garden" in the mail today and couldn't even get to the middle without gasping and LOVING everything!! This magazine seems to get better and better with every edition.
When I was the visual merchandiser at the Auckland BoConcept store, LeeAnn used to come in and select bits and pieces for her shoots. We used to all kind of twitter and whisper once she had gone…"did you know that she is a pilot?????" LeeAnn is gorgeous and creative…and not immediately "pilot like" (not sure what the pilot archetype is …but it wasn't LeeAnn!!) Anyway, I love her work and she is about it take on a new creative role as a consultant on TV2's show Trading Houses.
Photos by : Helen Bankers


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What are you doing? Words mouthed by Tom Tolbert as Gilbert Arenas was guarding him tightly. Tolbert was on the perimeter and wanted to shoot a three-pointer. Arenas guarded the old pro closely while Tolbert tried to get him to back down. Tolbert got the crowd involved by waving his arms. Arenas did not back down and Tolbert passed to Kerr who passed right back. Tolbert hoisted the three, but missed.
On the other end the battle continued, but this time it was Arenas egging on the crowd. Arenas then put a lethal crossover on Tolbert that left the big man frozen. With Tolbert's feet seemingly glued to the floor, Arenas blew by him for an easy dunk.
Gunner:Apparently no one told Jason Terry that a big night would not help the free agent garner a new contract. Terry scored 38 points and jacked up 24 three pointers. But then again maybe a big night will help. Terry made 12 threes.
New Role: Gilbert Arenas signed a six-year, $65 million contract in large part because he could play point guard. Washington Wizard players will be happy to know that he dished out 12 assists.
Best Shot: Joe McLean hit a halfcourt shot with just 1.1 seconds left in the game.
No-shows: Richard Jefferson and Mike Bibby are with Team USA in Puerto Rico, but tried to charter a plane to come to the event. They got a flight out of Puerto Rico, but could not fly back in time for their next game. Ben Davis and Anthony Cook were on the rosters but did not make it to the event.
Give a man a break: Kevin Flanagan had a first quarter bucket but the official scorer missed it and did not give him credit for taking a shot until the second half. Flanagan needed all the help he could get as he had the lowest career scoring average of any player in the All-Star game.
Best Dunks: Sean Elliott had a pair of nice stuffs, but it was 40-year old Pete Williams who brought down the house with a tomahawk slam.
Did Not Play: Miles Simon could not play due to a knee injury. His doctors have told him that he is two months ahead of schedule. He did attempt a shot when a ball landed in his lap on the bench and he shot it while still seated. He missed.
More Tolbert: After a foul, PA announcer Floyd Sedlmayr said, "Foul on Tolbert, Gilbert Arenas gets six shots." With the crowd laughing, Tolbert stormed towards the announce table.
Others In Attendance: Other former players in attendance, but not suited up included: Harvey Mason, Matt Muehlbach, Justin Wessel, John Ash, John Edgar, Kelvin Eafon and Justin Stewart. Other interesting people in attendance included former assistants Scott Thompson, Kevin O'Neal and Jay John.
On The Bench: The coach of the blue was former UA great Bob Elliott, while former Wildcat sharpshooter Joe Nehls coached the white team. Both are now Wildcat broadcasters.
Even More Tolbert: At times during the game music was left on the PA system following time-outs. Sweet Home Alabama was playing as Tolbert started to shoot a free throw. He motioned for the music to be turned down and the staff obliged. After he missed the free throw, he motioned for the music to be turned back up.
OUCH! Gene Edgerson, sporting a poofy, pony-tail thing, couldn't slow down while chasing after a loose ball and ran into Sean Elliott, knocking both into the baseline collection of photographers. Elliott got up slowly and acted like he hurt his back. The big question is why was Gene wearing knee pads on his ankles?
Rough Night: Center Ed Stokes was at the right place at the wrong time all night. His teammates tried to dish him the ball in a variety of fancy methods (no-look, behind the back, drive and dish) but most of the passes caught the big man off guard. He must have mishandled at least five passes.
\ Hot Streak: Jud Buechler missed his first shot, but made his next nine. He was especially effective on fast breaks.
Shut Out: Joe Turner was the only player not to score in the contest.
The Wookie: Before blocking the shot of Flanagan, Sean Rooks could be heard yelling "boo-ya". Later in the game he was called for the foul and stormed after the referee and as he glowered at the ref he yelled, "Aw c'mon, that was a good call."
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How much does it cost to remove this mole? (Photo)
Doctor Answers 2
Facial mole removals can run $500+.
Excision of the cheek lesion would run roughly $85 office visit + $500 for the excision under local.
Seeing an Expert = Priceless; Cosmetic Mole Removal
Cost will vary, but please go to a cosmetic dermatologist with experience in mole removal and lasers so you can limit the scarring. Lasers, radiowave or shave removal can be done for mole removal. See an Expert. Best, Dr. Emer
Learn more: https://www.youtube.com/channel/UCa6C2fuS-AgOnvBjr6_VSQg
These answers are for educational purposes and should not be relied upon as a substitute for medical advice you may receive from your physician. If you have a medical emergency, please call 911. These answers do not constitute or initiate a patient/doctor relationship.


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Constrained Invariant Motions for Networked Multi-Agent Systems
Franceschelli, Mauro
Egerstedt, Magnus B.
Giua, Alessandro
Mahulea, Cristian
MetadataShow full item record
In this paper we propose a methodology to solve the constrained consensus problem, i.e., the consensus problem for multi-agent systems with constrained dynamics. We propose a decentralized one-step horizon optimization problem to be solved iteratively by the agents to achieve rendezvous at the centroid of the network while ensuring the connectivity of the network and the feasibility of the agents motion respect to their constrained kinematics. We also provide simulations of the algorithm behavior.


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Lipomod™ 691P
Lipomod™ 691P is a mixed fungal lipase. Commonly, EMC is produced using lipases of animal origins, hence this fungal product is well suited to markets where animal-free alternatives are desired. Products made using this lipase may be sold to vegetarian and kosher markets. Lipomod™ 691P preferentially hydrolyses medium and long chain fatty acids.
Lipases hydrolyse triglycerides to liberate fatty acids. These fatty acids have strong flavour characteristics and are responsible for the flavours associated with cheese products. These enzymes are widespread throughout nature and have different degrees of activity to varying substrate triglycerides. For Enzyme Modified Cheese (EMC) they can be used to produce concentrated specific flavours. This product is an off-white to light brown powder.
- Data Sheet (英語)
- Food Enzyme Range (英語)
Biocatalysts manufactures specialty enzyme options and custom enzymes for Food, Beverage and Nutrition. Enzymes provide excellent benefits including increased yield and throughput, solving filtration problems, reduced waste and size of process plants and improving flavors and textures. Application can be found in dairy products, fruit and vegetable processing, functional protein manufacture, brewing and baking.
類別產品類型 Categories
- Additives ~ Food Enzymes ~ Hydrolases ~ Lipase
- Additives ~ Food Enzymes ~ Hydrolases ~ Glycosidase ~ Xylanase


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Treatment and prognosis of IgA nephropathy
- Authors
- Daniel C Cattran, MD
Daniel C Cattran, MD
- Professor of Medicine
- University of Toronto, Canada
- Gerald B Appel, MD
Gerald B Appel, MD
- Section Editor — Glomerular Diseases
- Professor of Medicine
- Columbia University College of Physicians and Surgeons
Topic Outline
- Section Editors
- Richard J Glassock, MD, MACP
Richard J Glassock, MD, MACP
- Editor-in-Chief — Nephrology
- Section Editor — Glomerular Diseases
- Emeritus Professor
- The David Geffen School of Medicine at UCLA
- Fernando C Fervenza, MD, PhD
Fernando C Fervenza, MD, PhD
- Section Editor — Glomerular Diseases
- Professor of Medicine
- Mayo Clinic College of Medicine
- Deputy Editor
- Albert Q Lam, MD
Albert Q Lam, MD
- Deputy Editor — Nephrology
- Assistant Professor of Medicine
- Harvard Medical School
IgA nephropathy is the most common cause of primary (idiopathic) glomerulonephritis in the developed world [1-6]. Although this disorder was initially thought to follow a benign course, it is now recognized that slow progression to end-stage renal disease occurs in up to 50 percent of affected patients [7], often over 20 to 25 years of observation. The remaining patients enter a sustained clinical remission or have persistent low-grade hematuria and/or proteinuria. Although the prognosis may be difficult to predict in some individuals, important risk factors for progressive renal disease have been identified. (See 'Clinical predictors of progression' below.)
There are two major clinical presentations of IgA nephropathy: gross hematuria, often recurrent, following shortly after an upper respiratory infection or athletic exertion; and persistent asymptomatic microscopic hematuria with or without mild to moderate proteinuria [5]. The diagnosis requires a kidney biopsy, which, as described below, often provides prognostic information. (See "Clinical presentation and diagnosis of IgA nephropathy" and 'Histologic predictors of progression' below.)
The renal prognosis and treatment of IgA nephropathy will be reviewed here. The pathogenesis of IgA nephropathy and the outcomes in patients who undergo renal transplantation are discussed separately. (See "Pathogenesis of IgA nephropathy" and "IgA nephropathy: Recurrence after transplantation".)
Patients with IgA nephropathy who have little or no proteinuria (less than 500 to 1000 mg/day) usually have a low risk of progression. However, progressive proteinuria and renal insufficiency develop in a substantial proportion of patients over the long term [7-12]. Among patients who develop overt proteinuria and/or an elevated serum creatinine concentration, progression to end-stage renal disease is approximately 15 to 25 percent at 10 years and 20 to 30 percent at 20 years [3,4,11-14].
The rate of progression is typically slow with the glomerular filtration rate (GFR) often falling by as little as 1 to 3 mL/min per year, a change not associated with an elevation in the serum creatinine concentration in the short term. Thus, a stable and normal serum creatinine concentration does not necessarily indicate stable disease. The frequency with which this occurs has been evaluated in studies in which repeat renal biopsy was used to assess the frequency of progressive disease [15,16]. In one report, repeat renal biopsies were performed at five years in 73 patients with persistent proteinuria and a normal or near-normal initial serum creatinine [15]. Histologic improvement occurred in only 4 percent, with 41 percent remaining stable and 55 percent showing progressive glomerular and secondary vascular and tubulointerstitial injury. An increase in serum creatinine to more than 1.5 mg/dL (133 micromol/L) was associated with major pathologic lesions.
Subscribers log in hereTo continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:Literature review current through: Jun 2017. | This topic last updated: May 09, 2017.The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.References
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- KDIGO. KDIGO Clinical Practice Guideline for Glomerulonephritis. Kidney Int Suppl 2012; 2:209. http://www.kdigo.org/clinical_practice_guidelines/pdf/KDIGO-GN-Guideline.pdf (Accessed on December 23, 2013).
- D'Amico G. Influence of clinical and histological features on actuarial renal survival in adult patients with idiopathic IgA nephropathy, membranous nephropathy, and membranoproliferative glomerulonephritis: survey of the recent literature. Am J Kidney Dis 1992; 20:315.
- Alamartine E, Sabatier JC, Guerin C, et al. Prognostic factors in mesangial IgA glomerulonephritis: an extensive study with univariate and multivariate analyses. Am J Kidney Dis 1991; 18:12.
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- Szeto CC, Lai FM, To KF, et al. The natural history of immunoglobulin a nephropathy among patients with hematuria and minimal proteinuria. Am J Med 2001; 110:434.
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- Hall CL, Bradley R, Kerr A, et al. Clinical value of renal biopsy in patients with asymptomatic microscopic hematuria with and without low-grade proteinuria. Clin Nephrol 2004; 62:267.
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- Donadio JV, Bergstralh EJ, Grande JP, Rademcher DM. Proteinuria patterns and their association with subsequent end-stage renal disease in IgA nephropathy. Nephrol Dial Transplant 2002; 17:1197.
- Reich HN, Troyanov S, Scholey JW, et al. Remission of proteinuria improves prognosis in IgA nephropathy. J Am Soc Nephrol 2007; 18:3177.
- Izzi C, Ravani P, Torres D, et al. IgA nephropathy: the presence of familial disease does not confer an increased risk for progression. Am J Kidney Dis 2006; 47:761.
- Frisch G, Lin J, Rosenstock J, et al. Mycophenolate mofetil (MMF) vs placebo in patients with moderately advanced IgA nephropathy: a double-blind randomized controlled trial. Nephrol Dial Transplant 2005; 20:2139.
- Le W, Liang S, Hu Y, et al. Long-term renal survival and related risk factors in patients with IgA nephropathy: results from a cohort of 1155 cases in a Chinese adult population. Nephrol Dial Transplant 2012; 27:1479.
- Maixnerova D, Bauerova L, Skibova J, et al. The retrospective analysis of 343 Czech patients with IgA nephropathy--one centre experience. Nephrol Dial Transplant 2012; 27:1492.
- Zhao YF, Zhu L, Liu LJ, et al. Measures of Urinary Protein and Albumin in the Prediction of Progression of IgA Nephropathy. Clin J Am Soc Nephrol 2016; 11:947.
- Wilson FP, Xie D, Anderson AH, et al. Urinary creatinine excretion, bioelectrical impedance analysis, and clinical outcomes in patients with CKD: the CRIC study. Clin J Am Soc Nephrol 2014; 9:2095.
- Fotheringham J, Campbell MJ, Fogarty DG, et al. Estimated albumin excretion rate versus urine albumin-creatinine ratio for the estimation of measured albumin excretion rate: derivation and validation of an estimated albumin excretion rate equation. Am J Kidney Dis 2014; 63:405.
- Haas M. Histologic subclassification of IgA nephropathy: a clinicopathologic study of 244 cases. Am J Kidney Dis 1997; 29:829.
- Vivante A, Afek A, Frenkel-Nir Y, et al. Persistent asymptomatic isolated microscopic hematuria in Israeli adolescents and young adults and risk for end-stage renal disease. JAMA 2011; 306:729.
- Ibels LS, Györy AZ. IgA nephropathy: analysis of the natural history, important factors in the progression of renal disease, and a review of the literature. Medicine (Baltimore) 1994; 73:79.
- Bennett WM, Kincaid-Smith P. Macroscopic hematuria in mesangial IgA nephropathy: correlation with glomerular crescents and renal dysfunction. Kidney Int 1983; 23:393.
- Packham DK, Hewitson TD, Yan HD, et al. Acute renal failure in IgA nephropathy. Clin Nephrol 1994; 42:349.
- Praga M, Gutierrez-Millet V, Navas JJ, et al. Acute worsening of renal function during episodes of macroscopic hematuria in IgA nephropathy. Kidney Int 1985; 28:69.
- Fogazzi GB, Imbasciati E, Moroni G, et al. Reversible acute renal failure from gross haematuria due to glomerulonephritis: not only in IgA nephropathy and not associated with intratubular obstruction. Nephrol Dial Transplant 1995; 10:624.
- Gutiérrez E, González E, Hernández E, et al. Factors that determine an incomplete recovery of renal function in macrohematuria-induced acute renal failure of IgA nephropathy. Clin J Am Soc Nephrol 2007; 2:51.
- Harden PN, Geddes C, Rowe PA, et al. Polymorphisms in angiotensin-converting-enzyme gene and progression of IgA nephropathy. Lancet 1995; 345:1540.
- Yoshida H, Mitarai T, Kawamura T, et al. Role of the deletion of polymorphism of the angiotensin converting enzyme gene in the progression and therapeutic responsiveness of IgA nephropathy. J Clin Invest 1995; 96:2162.
- Hunley TE, Julian BA, Phillips JA 3rd, et al. Angiotensin converting enzyme gene polymorphism: potential silencer motif and impact on progression in IgA nephropathy. Kidney Int 1996; 49:571.
- Suzuki S, Suzuki Y, Kobayashi Y, et al. Insertion/deletion polymorphism in ACE gene is not associated with renal progression in Japanese patients with IgA nephropathy. Am J Kidney Dis 2000; 35:896.
- Schena FP, D'Altri C, Cerullo G, et al. ACE gene polymorphism and IgA nephropathy: an ethnically homogeneous study and a meta-analysis. Kidney Int 2001; 60:732.
- Frimat L, Philippe C, Maghakian MN, et al. Polymorphism of angiotensin converting enzyme, angiotensinogen, and angiotensin II type 1 receptor genes and end-stage renal failure in IgA nephropathy: IGARAS--a study of 274 Men. J Am Soc Nephrol 2000; 11:2062.
- Pei Y, Scholey J, Thai K, et al. Association of angiotensinogen gene T235 variant with progression of immunoglobin A nephropathy in Caucasian patients. J Clin Invest 1997; 100:814.
- Xia YF, Huang S, Li X, et al. A family-based association study of megsin A23167G polymorphism with susceptibility and progression of IgA nephropathy in a Chinese population. Clin Nephrol 2006; 65:153.
- Schena FP, Cerullo G, Rossini M, et al. Increased risk of end-stage renal disease in familial IgA nephropathy. J Am Soc Nephrol 2002; 13:453.
- Bonnet F, Deprele C, Sassolas A, et al. Excessive body weight as a new independent risk factor for clinical and pathological progression in primary IgA nephritis. Am J Kidney Dis 2001; 37:720.
- Syrjänen J, Mustonen J, Pasternack A. Hypertriglyceridaemia and hyperuricaemia are risk factors for progression of IgA nephropathy. Nephrol Dial Transplant 2000; 15:34.
- Yamamoto R, Nagasawa Y, Shoji T, et al. Cigarette smoking and progression of IgA nephropathy. Am J Kidney Dis 2010; 56:313.
- Daniel L, Saingra Y, Giorgi R, et al. Tubular lesions determine prognosis of IgA nephropathy. Am J Kidney Dis 2000; 35:13.
- Lai FM, Szeto CC, Choi PC, et al. Primary IgA nephropathy with low histologic grade and disease progression: is there a "point of no return"? Am J Kidney Dis 2002; 39:401.
- Weber CL, Rose CL, Magil AB. Focal segmental glomerulosclerosis in mild IgA nephropathy: a clinical-pathologic study. Nephrol Dial Transplant 2009; 24:483.
- Lee HS, Lee MS, Lee SM, et al. Histological grading of IgA nephropathy predicting renal outcome: revisiting H. S. Lee's glomerular grading system. Nephrol Dial Transplant 2005; 20:342.
- Manno C, Strippoli GF, D'Altri C, et al. A novel simpler histological classification for renal survival in IgA nephropathy: a retrospective study. Am J Kidney Dis 2007; 49:763.
- Working Group of the International IgA Nephropathy Network and the Renal Pathology Society, Cattran DC, Coppo R, et al. The Oxford classification of IgA nephropathy: rationale, clinicopathological correlations, and classification. Kidney Int 2009; 76:534.
- Working Group of the International IgA Nephropathy Network and the Renal Pathology Society, Roberts IS, Cook HT, et al. The Oxford classification of IgA nephropathy: pathology definitions, correlations, and reproducibility. Kidney Int 2009; 76:546.
- El Karoui K, Hill GS, Karras A, et al. Focal segmental glomerulosclerosis plays a major role in the progression of IgA nephropathy. II. Light microscopic and clinical studies. Kidney Int 2011; 79:643.
- Herzenberg AM, Fogo AB, Reich HN, et al. Validation of the Oxford classification of IgA nephropathy. Kidney Int 2011; 80:310.
- Shi SF, Wang SX, Jiang L, et al. Pathologic predictors of renal outcome and therapeutic efficacy in IgA nephropathy: validation of the oxford classification. Clin J Am Soc Nephrol 2011; 6:2175.
- Working Group of the International IgA Nephropathy Network and the Renal Pathology Society, Coppo R, Troyanov S, et al. The Oxford IgA nephropathy clinicopathological classification is valid for children as well as adults. Kidney Int 2010; 77:921.
- Edström Halling S, Söderberg MP, Berg UB. Predictors of outcome in paediatric IgA nephropathy with regard to clinical and histopathological variables (Oxford classification). Nephrol Dial Transplant 2012; 27:715.
- Tanaka S, Ninomiya T, Katafuchi R, et al. Development and validation of a prediction rule using the Oxford classification in IgA nephropathy. Clin J Am Soc Nephrol 2013; 8:2082.
- Zhao N, Hou P, Lv J, et al. The level of galactose-deficient IgA1 in the sera of patients with IgA nephropathy is associated with disease progression. Kidney Int 2012; 82:790.
- Berthoux F, Suzuki H, Thibaudin L, et al. Autoantibodies targeting galactose-deficient IgA1 associate with progression of IgA nephropathy. J Am Soc Nephrol 2012; 23:1579.
- Barratt J, Feehally J. Treatment of IgA nephropathy. Kidney Int 2006; 69:1934.
- Appel GB, Waldman M. The IgA nephropathy treatment dilemma. Kidney Int 2006; 69:1939.
- Reid S, Cawthon PM, Craig JC, et al. Non-immunosuppressive treatment for IgA nephropathy. Cochrane Database Syst Rev 2011; :CD003962.
- Kunz R, Friedrich C, Wolbers M, Mann JF. Meta-analysis: effect of monotherapy and combination therapy with inhibitors of the renin angiotensin system on proteinuria in renal disease. Ann Intern Med 2008; 148:30.
- Maschio G, Cagnoli L, Claroni F, et al. ACE inhibition reduces proteinuria in normotensive patients with IgA nephropathy: a multicentre, randomized, placebo-controlled study. Nephrol Dial Transplant 1994; 9:265.
- Bakris GL, Weir MR, Secic M, et al. Differential effects of calcium antagonist subclasses on markers of nephropathy progression. Kidney Int 2004; 65:1991.
- Remuzzi A, Perticucci E, Ruggenenti P, et al. Angiotensin converting enzyme inhibition improves glomerular size-selectivity in IgA nephropathy. Kidney Int 1991; 39:1267.
- Kanno Y, Okada H, Saruta T, Suzuki H. Blood pressure reduction associated with preservation of renal function in hypertensive patients with IgA nephropathy: a 3-year follow-up. Clin Nephrol 2000; 54:360.
- Praga M, Gutiérrez E, González E, et al. Treatment of IgA nephropathy with ACE inhibitors: a randomized and controlled trial. J Am Soc Nephrol 2003; 14:1578.
- Li PK, Leung CB, Chow KM, et al. Hong Kong study using valsartan in IgA nephropathy (HKVIN): a double-blind, randomized, placebo-controlled study. Am J Kidney Dis 2006; 47:751.
- Coppo R, Peruzzi L, Amore A, et al. IgACE: a placebo-controlled, randomized trial of angiotensin-converting enzyme inhibitors in children and young people with IgA nephropathy and moderate proteinuria. J Am Soc Nephrol 2007; 18:1880.
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- Retraction--Combination treatment of angiotensin-II receptor blocker and angiotensin-converting-enzyme inhibitor in non-diabetic renal disease (COOPERATE): a randomised controlled trial. Lancet 2009; 374:1226.
- ONTARGET Investigators, Yusuf S, Teo KK, et al. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med 2008; 358:1547.
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- Donadio JV Jr, Bergstralh EJ, Offord KP, et al. A controlled trial of fish oil in IgA nephropathy. Mayo Nephrology Collaborative Group. N Engl J Med 1994; 331:1194.
- Alexopoulos E, Stangou M, Pantzaki A, et al. Treatment of severe IgA nephropathy with omega-3 fatty acids: the effect of a "very low dose" regimen. Ren Fail 2004; 26:453.
- Donadio JV Jr, Larson TS, Bergstralh EJ, Grande JP. A randomized trial of high-dose compared with low-dose omega-3 fatty acids in severe IgA nephropathy. J Am Soc Nephrol 2001; 12:791.
- Donadio JV Jr, Grande JP, Bergstralh EJ, et al. The long-term outcome of patients with IgA nephropathy treated with fish oil in a controlled trial. Mayo Nephrology Collaborative Group. J Am Soc Nephrol 1999; 10:1772.
- Bennett WM, Walker RG, Kincaid-Smith P. Treatment of IgA nephropathy with eicosapentanoic acid (EPA): a two-year prospective trial. Clin Nephrol 1989; 31:128.
- Pettersson EE, Rekola S, Berglund L, et al. Treatment of IgA nephropathy with omega-3-polyunsaturated fatty acids: a prospective, double-blind, randomized study. Clin Nephrol 1994; 41:183.
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- Alexopoulos E. Treatment of primary IgA nephropathy. Kidney Int 2004; 65:341.
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- Ballardie FW. IgA nephropathy treatment 25 years on: can we halt progression? The evidence base. Nephrol Dial Transplant 2004; 19:1041.
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- Locatelli F, Del Vecchio L, Pozzi C. The patient with IgA glomerulonephritis--what is the role of steroid treatment? Nephrol Dial Transplant 1999; 14:1057.
- Lv J, Xu D, Perkovic V, et al. Corticosteroid therapy in IgA nephropathy. J Am Soc Nephrol 2012; 23:1108.
- Rauen T, Eitner F, Fitzner C, et al. Intensive Supportive Care plus Immunosuppression in IgA Nephropathy. N Engl J Med 2015; 373:2225.
- Pozzi C, Bolasco PG, Fogazzi GB, et al. Corticosteroids in IgA nephropathy: a randomised controlled trial. Lancet 1999; 353:883.
- Pozzi C, Andrulli S, Del Vecchio L, et al. Corticosteroid effectiveness in IgA nephropathy: long-term results of a randomized, controlled trial. J Am Soc Nephrol 2004; 15:157.
- Manno C, Torres DD, Rossini M, et al. Randomized controlled clinical trial of corticosteroids plus ACE-inhibitors with long-term follow-up in proteinuric IgA nephropathy. Nephrol Dial Transplant 2009; 24:3694.
- Lai KN, Lai FM, Ho CP, Chan KW. Corticosteroid therapy in IgA nephropathy with nephrotic syndrome: a long-term controlled trial. Clin Nephrol 1986; 26:174.
- Mustonen J, Pasternack A, Rantala I. The nephrotic syndrome in IgA glomerulonephritis: response to corticosteroid therapy. Clin Nephrol 1983; 20:172.
- Cheng IK, Chan KW, Chan MK. Mesangial IgA nephropathy with steroid-responsive nephrotic syndrome: disappearance of mesangial IgA deposits following steroid-induced remission. Am J Kidney Dis 1989; 14:361.
- Woo KT, Lee GS, Lau YK, et al. Effects of triple therapy in IgA nephritis: a follow-up study 5 years later. Clin Nephrol 1991; 36:60.
- Walker RG, Yu SH, Owen JE, Kincaid-Smith P. The treatment of mesangial IgA nephropathy with cyclophosphamide, dipyridamole and warfarin: a two-year prospective trial. Clin Nephrol 1990; 34:103.
- Ballardie FW, Roberts IS. Controlled prospective trial of prednisolone and cytotoxics in progressive IgA nephropathy. J Am Soc Nephrol 2002; 13:142.
- Yoshikawa N, Ito H, Sakai T, et al. A controlled trial of combined therapy for newly diagnosed severe childhood IgA nephropathy. The Japanese Pediatric IgA Nephropathy Treatment Study Group. J Am Soc Nephrol 1999; 10:101.
- Yoshikawa N, Honda M, Iijima K, et al. Steroid treatment for severe childhood IgA nephropathy: a randomized, controlled trial. Clin J Am Soc Nephrol 2006; 1:511.
- Pozzi C, Andrulli S, Pani A, et al. Addition of azathioprine to corticosteroids does not benefit patients with IgA nephropathy. J Am Soc Nephrol 2010; 21:1783.
- Floege J, Eitner F. Combined immunosuppression in high-risk patients with IgA nephropathy? J Am Soc Nephrol 2010; 21:1604.
- Kamei K, Nakanishi K, Ito S, et al. Long-term results of a randomized controlled trial in childhood IgA nephropathy. Clin J Am Soc Nephrol 2011; 6:1301.
- Welch TR, McAdams AJ, Berry A. Rapidly progressive IgA nephropathy. Am J Dis Child 1988; 142:789.
- Lai KN, Lai FM, Leung AC, et al. Plasma exchange in patients with rapidly progressive idiopathic IgA nephropathy: a report of two cases and review of literature. Am J Kidney Dis 1987; 10:66.
- Roccatello D, Ferro M, Coppo R, et al. Report on intensive treatment of extracapillary glomerulonephritis with focus on crescentic IgA nephropathy. Nephrol Dial Transplant 1995; 10:2054.
- McIntyre CW, Fluck RJ, Lambie SH. Steroid and cyclophosphamide therapy for IgA nephropathy associated with crescenteric change: an effective treatment. Clin Nephrol 2001; 56:193.
- Tumlin JA, Lohavichan V, Hennigar R. Crescentic, proliferative IgA nephropathy: clinical and histological response to methylprednisolone and intravenous cyclophosphamide. Nephrol Dial Transplant 2003; 18:1321.
- Galla JH. IgA nephropathy. Kidney Int 1995; 47:377.
- Maes BD, Oyen R, Claes K, et al. Mycophenolate mofetil in IgA nephropathy: results of a 3-year prospective placebo-controlled randomized study. Kidney Int 2004; 65:1842.
- Chen X, Chen P, Cai G, et al. [A randomized control trial of mycophenolate mofeil treatment in severe IgA nephropathy]. Zhonghua Yi Xue Za Zhi 2002; 82:796.
- Tang SC, Tang AW, Wong SS, et al. Long-term study of mycophenolate mofetil treatment in IgA nephropathy. Kidney Int 2010; 77:543.
- Dal Canton A, Amore A, Barbano G, et al. One-year angiotensin-converting enzyme inhibition plus mycophenolate mofetil immunosuppression in the course of early IgA nephropathy: a multicenter, randomised, controlled study. J Nephrol 2005; 18:136.
- Lai KN, Lai FM, Li PK, Vallance-Owen J. Cyclosporin treatment of IgA nephropathy: a short term controlled trial. Br Med J (Clin Res Ed) 1987; 295:1165.
- Cattran DC. Current status of cyclosporin A in the treatment of membranous, IgA and membranoproliferative glomerulonephritis. Clin Nephrol 1991; 35 Suppl 1:S43.
- Chábová V, Tesar V, Zabka J, et al. Long term treatment of IgA nephropathy with cyclosporine A. Ren Fail 2000; 22:55.
- Kim YC, Chin HJ, Koo HS, Kim S. Tacrolimus decreases albuminuria in patients with IgA nephropathy and normal blood pressure: a double-blind randomized controlled trial of efficacy of tacrolimus on IgA nephropathy. PLoS One 2013; 8:e71545.
- Shin JI, Park JM, Shin YH, et al. Cyclosporin A therapy for severe Henoch-Schönlein nephritis with nephrotic syndrome. Pediatr Nephrol 2005; 20:1093.
- Park JM, Won SC, Shin JI, et al. Cyclosporin A therapy for Henoch-Schönlein nephritis with nephrotic-range proteinuria. Pediatr Nephrol 2011; 26:411.
- Lafayette RA, Canetta PA, Rovin BH, et al. A Randomized, Controlled Trial of Rituximab in IgA Nephropathy with Proteinuria and Renal Dysfunction. J Am Soc Nephrol 2017; 28:1306.
- Szeto CC, Chow KM, Kwan BC, et al. Oral calcitriol for the treatment of persistent proteinuria in immunoglobulin A nephropathy: an uncontrolled trial. Am J Kidney Dis 2008; 51:724.
- Fishbane S, Chittineni H, Packman M, et al. Oral paricalcitol in the treatment of patients with CKD and proteinuria: a randomized trial. Am J Kidney Dis 2009; 54:647.
- Liu LJ, Lv JC, Shi SF, et al. Oral calcitriol for reduction of proteinuria in patients with IgA nephropathy: a randomized controlled trial. Am J Kidney Dis 2012; 59:67.
- Tomino Y, Sakai H, Hanzawa S, et al. Clinical effect of danazol in patients with IgA nephropathy. Jpn J Med 1987; 26:162.
- Béné MC, Faure GC, Hurault de Ligny B, de March AK. Clinical involvement of the tonsillar immune system in IgA nephropathy. Acta Otolaryngol Suppl 2004; :10.
- Xie Y, Chen X, Nishi S, et al. Relationship between tonsils and IgA nephropathy as well as indications of tonsillectomy. Kidney Int 2004; 65:1135.
- Hotta O, Miyazaki M, Furuta T, et al. Tonsillectomy and steroid pulse therapy significantly impact on clinical remission in patients with IgA nephropathy. Am J Kidney Dis 2001; 38:736.
- Xie Y, Nishi S, Ueno M, et al. The efficacy of tonsillectomy on long-term renal survival in patients with IgA nephropathy. Kidney Int 2003; 63:1861.
- Akagi H, Kosaka M, Hattori K, et al. Long-term results of tonsillectomy as a treatment for IgA nephropathy. Acta Otolaryngol Suppl 2004; :38.
- Komatsu H, Fujimoto S, Hara S, et al. Effect of tonsillectomy plus steroid pulse therapy on clinical remission of IgA nephropathy: a controlled study. Clin J Am Soc Nephrol 2008; 3:1301.
- Rasche FM, Schwarz A, Keller F. Tonsillectomy does not prevent a progressive course in IgA nephropathy. Clin Nephrol 1999; 51:147.
- Rasche FM, Sailer LC, Czock D, Keller F. Tonsillectomy, high dose immunoglobulins, and cyclophosphamide in progressive IgA-nephropathy. Acta Otolaryngol Suppl 2004; :32.
- Kawamura T, Yoshimura M, Miyazaki Y, et al. A multicenter randomized controlled trial of tonsillectomy combined with steroid pulse therapy in patients with immunoglobulin A nephropathy. Nephrol Dial Transplant 2014; 29:1546.
- Zand L, Fervenza FC. Does tonsillectomy have a role in the treatment of patients with immunoglobulin A nephropathy? Nephrol Dial Transplant 2014; 29:1456.
- Wang Y, Chen J, Wang Y, et al. A meta-analysis of the clinical remission rate and long-term efficacy of tonsillectomy in patients with IgA nephropathy. Nephrol Dial Transplant 2011; 26:1923.
- Ferri C, Puccini R, Longombardo G, et al. Low-antigen-content diet in the treatment of patients with IgA nephropathy. Nephrol Dial Transplant 1993; 8:1193.
- Coppo R, Roccatello D, Amore A, et al. Effects of a gluten-free diet in primary IgA nephropathy. Clin Nephrol 1990; 33:72.
- Rostoker G, Pech MA, Del Prato S, et al. Serum IgG subclasses and IgM imbalances in adult IgA mesangial glomerulonephritis and idiopathic Henoch-Schoenlein purpura. Clin Exp Immunol 1989; 75:30.
- Rostoker G, Desvaux-Belghiti D, Pilatte Y, et al. High-dose immunoglobulin therapy for severe IgA nephropathy and Henoch-Schönlein purpura. Ann Intern Med 1994; 120:476.
- Smerud HK, Bárány P, Lindström K, et al. New treatment for IgA nephropathy: enteric budesonide targeted to the ileocecal region ameliorates proteinuria. Nephrol Dial Transplant 2011; 26:3237.
- Fellström BC, Barratt J, Cook H, et al. Targeted-release budesonide versus placebo in patients with IgA nephropathy (NEFIGAN): a double-blind, randomised, placebo-controlled phase 2b trial. Lancet 2017.
- Liu Y, Ma X, Lv J, et al. Risk factors for pregnancy outcomes in patients with IgA nephropathy: a matched cohort study. Am J Kidney Dis 2014; 64:730.
- Abe S. Pregnancy in IgA nephropathy. Kidney Int 1991; 40:1098.
- Abe S. The influence of pregnancy on the long-term renal prognosis of IgA nephropathy. Clin Nephrol 1994; 41:61.
- Clinical predictors of progression
- - Reduced GFR
- - Hypertension
- - Protein excretion above 1 g/day
- Acute onset of nephrotic syndrome
- - Hematuria without proteinuria
- - Acute kidney injury with gross hematuria
- - Genetic associations
- - Other risk factors
- Histologic predictors of progression
- - Oxford classification of IgA nephropathy
- Absolute renal risk score
- Serologic predictors of progression
- Patient selection
- Monitoring disease activity
- Angiotensin inhibition
- - Efficacy
- - Combination of ACE inhibitor and ARB
- Proteinuria and blood pressure goals
- Lipid-lowering therapy
- Fish oil
- Indications for glucocorticoid therapy
- - Lack of benefit in chronic fibrotic disease
- Glucocorticoids as sole immunosuppressive/anti-inflammatory therapy
- - Glucocorticoid regimen
- - Patients with apparent minimal change disease
- Combined immunosuppressive therapy
- - Severe or progressive disease
- Glucocorticoids plus cyclophosphamide followed by azathioprine
- Glucocorticoids plus azathioprine
- Severe disease in children
- - Crescentic glomerulonephritis
- Unclear role for other immunosuppressive agents
- - Mycophenolate mofetil
- - Calcineurin inhibitors
- - Rituximab
- Tonsillectomy
- Low-antigen diet
- Intravenous immune globulin
- Budesonide
- Background
- Management


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Product Safety Testing: A Brief Background
In 1933, at least 17 American women were blinded by, and one died of, complications resulting from the use of Lash Lure, a new mascara. At that time, no laws or regulations governed the safety of consumer products. Manufacturers were free to market almost anything.
As a result of this and other tragic incidents related to untested products, the U.S. Congress passed the Federal Food, Drug, and Cosmetic Act of 1938, requiring that food, drugs, and cosmetics be verified as safe for human use before they could be sold. Following this, animals came nito widespread use as the mechanism for testing the safety of personal care products in the United States. This was based on the premise that animals are similar enough to people to be used as models for human response.
Today, the federal government still requires manufacturers to establish product safety. Personal care products covered by federal laws include shampoo, deodorant, eye shadow, lipstick, nail polish, hair spray, perfume, toothpaste, shaving cream, sunscreen, and hand lotion. Some of these are regulated as cosmetics; others — including certain sunscreens, fluoride toothpastes, and antiperspirants that claim some medicinal value — are regulated as over-the-counter drugs.
The Ethical Dilemma
The public has become increasingly aware of the potential of some chemicals to harm humans, wildlife, and the environment. Lawmakers have pushed hard for strict product safety standards; unfortunately, these can often come at the expense of lab animals. At the same time, many people have grown concerned about the potential for animal suffering in product testing labs.
The MSPCA believes this dilemma can be resolved through the continued development of alternative test methods that dramatically reduce the number of animals used in labs today. And, perhaps, this may eventually lead to their complete elimination – while providing the public with vital product safety assurances.
The Role of Animals
Because the Animal Welfare Act (AWA) does not require that all laboratory animal use in the U.S. be reported (it exempts mice, rats, and birds), exact numbers are impossible to obtain. It has been estimated that millions of animals per year are used to test the safety of cosmetics, household cleaners, pesticides, industrial chemicals, food additives, packing materials, drugs and vaccines for both people and animals, and even the food eaten by companion animals.
Government statistics indicate that product safety testing accounts for approximately 5% percent of all animal use for scientific purposes. This amounts to many millions of animals per year, worldwide. Tens of millions more are used in education and in basic biomedical research, including the development of new drugs and vaccines.
About 95-98% of the animals used in testing are mice, rats, and other rodents such as guinea pigs and hamsters; in addition, rabbits, dogs, cats, nonhuman primates, birds, fish, and amphibians are also used. During a product test, a group of animals is exposed to a test substance in various ways: by application to an eye or a patch of shaved skin, in their food or drinking water, by inhalation, or by addition to the water in which they live. Another group of the same species, the control, is left unexposed to the test substance. The condition of the exposed animals is then compared with this control group. According to Humane Society International, the registration of a single pesticide requires more than 50 experiments and the use of as many as 12,000 animals. They also note that, according to the Food and Drug Administration, nine out of ten pharmaceuticals that pass the animal testing stage are eventually abandoned, as they fail to pass clinical studies on humans.
Some animals experience little or no discomfort in their lives as test subjects, others experience temporary pain, and still others experience extreme pain for prolonged periods of time. The amount of suffering caused during any project depends upon many factors, including the substance being tested, the type of test, the number of animals being used, whether anesthetics or pain-killing drugs are administered, the animals' housing, and how they are killed at the end of the test, if that is the final outcome.
Toxicology – Predicting the Potential for Harm
Toxicology is the study of the harmful effects of chemical substances on living organisms. It is a complex science because something that is safe for use at one level of exposure can be harmful at just a slightly higher level. All matter – even water – can be harmful at some exposure level. The toxicologist's job is to determine the probability and extent to which a particular substance will be harmful to plants, animals, or humans under various exposure conditions. This complicates matters further because a chemical that is harmful to one species is not always harmful to another. Tens of thousands of chemicals are likely in current use in the United States, with thousands more introduced each year. American industry spends billions of dollars annually on toxicology studies in an effort to protect living beings from harm. Toxicology tests conducted on animals are also time-consuming: according to the Humane Society International, evaluating a single pesticide chemical by testing on rodents can take as long as five years.
Types of Tests
Many kinds of toxicity tests have been developed to assess the risks associated with routine or accidental exposure to various products. Adverse effects from these exposures are known as "clinical endpoints" and can include skin or eye irritation or corrosion, reproductive or developmental toxicity, development of cancers, or impacts on the neurological systems, to name a few. The species and number of animals used in these tests depend upon the type of toxicity being assessed.
In addition to understanding the effects of exposure, toxicity tests also measure different durations of exposure: acute, subchronic, and chronic.
Acute toxicity tests assess the risk of short-term – usually a single or brief – exposure through normal use or accidental contact. Two examples of these tests are the much-publicized LD50 (lethal dose 50 percent) test, which estimates the dose of a substance needed to kill half of a group of rats or other test animals, and the Draize eye and skin irritancy tests, which use rabbits to estimate the ability of a test substance to irritate or damage these organs.
Subchronic toxicity tests are used to determine toxicity from repeated exposure to a chemical over a period of several weeks to several months. These tests usually last less than 10% of the test subjects' (typically rats) natural life span. Subchronic toxicity tests are used to measure the toxicity in chemicals, food additives, and even common spices such as paprika. Hydroquinone, a chemical commonly used in skin lightening, age spot, and blemish creams, was also tested using these tests. At the end of the exposure period, the animals are often killed so that their organs may be examined.
Chronic toxicity tests assess risks of long-term exposure – often at low levels for a substantial portion of the test subjects' life – such as the potential to cause cancer, birth defects, and developmental abnormalities. They may also explore the body's absorption, distribution, metabolism, storage, and excretion of new chemicals and products, and/or monitor the long-term effect of a chemical on the brain, DNA, and nervous system. Lifetime animal-feeding studies, such as those conducted over the two-year lifetime of a rat or the 18-month lifetime of a mouse, are examples of chronic-toxicity tests. Like in subchronic toxicity tests, these animals are typically killed after the test is over.
While data searches and various other non-animal tests can now be used to determine the toxicity of some substances before they reach the animal-testing stage, animal tests are still widely used as a line of defense against potentially harmful products. Animal tests also precede human tests in evaluating the safety of human drugs and vaccines. Many state and federal laws depend on specific animal test data to identify and classify potentially hazardous substances released into our air, food, and water supplies.
Trends in Consumer Product Safety Testing
Ironically, consumer interest in "green" products has increased the amount of animal testing as manufacturers attempt to develop new, less environmentally harmful products. The push for new products to meet the needs of the developing world, such as affordable toothpaste for people living in poverty, has also increased animal testing. Furthermore, the rise of breeding genetically engineered or modified animals, particularly mice, has led to these animals' routine use in biomedical research and testing.
Overall, however, the number of animals used to test cosmetics and other personal-care products has declined in recent years. U.S. government statistics show an 8% drop in the number of animals used in labs since 2014, which may have occurred because of the following reasons: many ingredients have already been proven safe through years of animal tests and human use, companies are now more apt to share test results, and a wide array of non-animal skin and eye irritation tests (including synthetic skin and eye models) have been developed to determine the effects of short-term exposure to new ingredients. Public pressure has played a major role in the development of these alternatives.
Today, it is increasingly likely that some combination of alternative tests will be used, at least initially, to screen out potentially harmful substances before they reach the animal testing stage. A 2011 survey by the Leaping Bunny Program found that 67% of people oppose the use of animals in cosmetics testing, and a 2013 poll sponsored by the Humane Society of the United States found that two-thirds of American voters opposed cosmetics testing.
Some of the largest multi-national consumer products manufacturers, such as Procter & Gamble and L'Oréal have developed alternatives, responding to the public's support of ending animal testing. For example, L'Oréal's human skin model, EPISKIN, was validated by the European Centre for the Validation of Alternative Methods (ECVAM) in 2007 as an alternative to skin irritation tests performed on animals. Often, these tests are then used by smaller companies that sell products labeled "cruelty-free" or "not tested on animals" (see Cruelty-Free Labeling).
Laws and Regulations
While federal laws don't always require animal tests, many indirectly influence testing procedures through regulations and guidelines. For example, the Food and Drug Administration (FDA) requires that drugs, vaccines, and medical devices be both "safe" and "effective" and that labeling claims be substantiated.
Unfortunately, animal test results are now well established as the international standard for assessing product safety. Because countries differ widely on the degree to which they will consider alternative test results for products sold within their borders, this can result in frustration and red tape for multinational companies interested in alternative test methods, as their efforts to use non-traditional, non-animal safety data can thus become stymied. For example, in China, laws require that cosmetics are tested on animals before they can be approved, which has created an obstacle for many "cruelty-free" companies looking to expand into the Chinese market.
In the US, some progress is being made at the state level. California, New Jersey, and New York each have laws limiting the use of animals in product testing. They require that if an appropriate non-animal test has been validated by the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), it must be used in lieu of animal-based testing. (Please see below for more information on validation and ICCVAM.)
Alternatives Development
In response to increasing interest in reducing animal use in product safety testing, a growing number of alternative tests have been developed that replace, reduce, or refine animal tests (see Lab Animal Alternatives: The Three Rs).
In vitro tests (involving cell and tissue cultures grown "in glass" in the laboratory) are among the alternatives showing the most promise in product testing. They are faster, cheaper, and often more reliable than animal tests: for example, a Draize rabbit skin corrosion test may cost $1800, whereas a test using an in vitro human tissue model such as EpiDerm costs approximately $800 and more accurately shows the effects of a chemical or product on human skin. Some of these in vitro tests completely replace animals while others reduce their numbers. Additionally, tests that are in silico (computer-based) have also reduced the numbers of animals used. While these methods often eliminate the need for animals in the early stages of research, animals are often needed in later stages of product development. Still other alternatives, called refinements, make tests less painful or stressful for the animals involved.
The Issues of Validation and Acceptance
Many promising alternative test methods have been developed for product testing since the early 1980s. Widespread acceptance of them, however, has been slow. Scientists say time is needed to confirm the reliability of new tests – that is, to determine if they produce the same results in every laboratory every time – and to build consensus among scientists on which tests best suit different purposes. This entire process is referred to as scientific validation.
Once scientists are convinced that a new alternative does provide sound safety information for a product, such as hair color, the government agency responsible for assuring hair color safety must be persuaded to accept the new test as a valid alternative to the existing whole animal test. To date, national and international regulatory agencies have been very slow to respond. Until alternatives are officially accepted by these agencies, further progress toward eliminating animal use in all product safety testing will remain slow.
The European Union (EU) has taken the lead in seeking alternatives to using animals in product safety testing for personal care products. In 2004, the EU implemented a directive banning the testing of finished cosmetic products and their component ingredients on animals. In 2009 it was expanded to include a ban on marketing cosmetics in which the final product, or any of its ingredients, have been tested on animals. In 2013,the EU enacted a full ban on the import, sale, and marketing of any cosmetics that were tested on animals and continues to actively work towards animal-free testing alternatives. Many hope this will encourage the development of alternatives that can be validated and approved for use in the US and other countries.
Because of this, it is essential for both consumers and manufacturers to put pressure on governments to validate alternatives already in use or in development.
The ICCVAM Act
A promising development in the effort to replace, reduce, and refine traditional animal research came with the 1993 passage of the National Institutes of Health (NIH) Revitalization Act, which required the government to develop an alternatives validation and acceptance program. Passage of this act was largely the work of a powerful coalition of animal advocates (including the MSPCA) and several academic and industry groups.
As a result of this mandate, the Interagency Coordinating Committee for the Validation of Alternative Methods (ICCVAM) was formed the following year. In 2000, the ICCVAM Authorization Act passed, making it a permanent committee under the NIH. ICCVAM is charged with establishing criteria for scientific validation and regulatory acceptance of new tests, including alternative methods that can reduce or eliminate the use of animals in safety testing. ICCVAM then encourages the government agencies involved in regulating toxicity testing to accept the new testing methods. ICCVAM also works to reduce the use of animals in toxicological testing by sharing information among agencies to reduce duplicative tests.
ICCVAM members include federal agencies involved in animal testing, such as the Food and Drug Administration, the Environmental Protection Agency, the Consumer Product Safety Commission, and the Occupational Safety and Health Administration. These agencies work closely with other international agencies, such as the European Center for the Validation of Alternative Methods (ECVAM), to coordinate validation efforts on an international level. In recent years, the collaboration between ICCVAM and ECVAM has been strengthened. Sometimes a member of ICCVAM sits on ECVAM (and vice versa); the groups have also collaborated on ongoing peer reviews of alternative test methods and have jointly conducted several studies and workshops. The two groups have also formed an International Cooperation on Alternative Test Methods (ICATM) with the Japanese Center for Validation of Alternative Methods (JaCVAM) and Health Canada to work towards coordinating scientific validation on non-animal toxicity test methods.
Since its inception, ICCVAM has recommended a handful of alternative tests for regulatory agency acceptance. One, called the Local Lymph Node Assay (LLNA), is used to determine if a new chemical is likely to cause allergic skin reactions. The LLNA is both a reduction and a refinement. It tests mice instead of guinea pigs, uses far fewer animals, and results in much less pain and distress. Examples of replacements for animal testing include Corrositex, which replaced rabbits with a synthetic skin test that is used to assess how damaging a chemical is to the skin, and the Bovine Corneal Opacity and Permeability (BCOP) and the Isolated Chicken Eye (ICE) Corrositex tests, which utilize tissues obtained from slaughterhouses to replace the use of live animals.
In addition, ICCVAM has recommended replacements or refinements in the fields of acute systemic toxicity, biologics testing, developmental toxicity, endocrine disruptors, eye corrosion/irritation, genetic toxicity, pyrogenicity, skin corrosion, skin irritation, and skin sensitization.
ICCVAM has been criticized for not making enough progress since its inception. Some suggest the committee's process for reviewing alternatives is cumbersome and slow, not enough focus has been placed on replacement (rather than refinement and reduction), and insufficient resources have been provided to advance more alternative methods. In 2008, at the request of Congress, ICCVAM released a five-year plan identifying areas of high priority for non-animal and alternative tests, and in 2013, another five-year plan was drafted. While there have been some revisions to the original 2008 plan that reflect progress in science and technology, ICCVAM's central goals have generally remained the same: ICCVAM hopes to advance the use of alternatives in the US, foster acceptance and appropriate use of alternative test methods, and develop partnerships and strengthen interactions with stakeholders. Despite ICCVAM's commitment to developing alternative testing methods and strategies moving forward, however, many of ICCVAM's recommended methods still have yet to achieve regulatory use in testing facilities.
Federal Agencies Regulating Testing
Fifteen federal agencies play a role in animal testing for regulatory purposes; similar agencies exist in other countries. Four of the most significant in the United States are the Food and Drug Administration, the Environmental Protection Agency, the Consumer Product Safety Commission, and the Occupational Safety and Health Administration.
The Food and Drug Administration (FDA) requires that drugs, vaccines, and medical devices be both "safe" and "effective" and that labeling claims be substantiated. A wide variety of products are regulated by the FDA, including animal and human food and drugs, medical devices, cosmetics, color additives, electronic products, and animal organs and tissues intended for transplantation into humans. The FDA has no authority to require testing of cosmetics for safety, except for their color additives. However, by regulation, the FDA has stated that any cosmetic product or ingredient not substantiated for safety must bear a prominent label stating the safety of the product has not been determined. Clearly, this is not a label most manufacturers would willingly place on their products.
The Environmental Protection Agency (EPA) administers many laws designed to protect our environment, including the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), the Toxic Substances Control Act (TSCA), the Clean Air Act, and the Clean Water Act. FIFRA is designed to protect human health and the environment from the adverse effects of pesticides. TSCA regulates the use of any new chemicals that might be added to everyday consumer products. Animals used for food crop pesticide tests — and even household pesticide (bug spray, rat poison, etc) tests — are often subjected to lethal dose tests, in which they must be exposed to or forced to swallow massive quantities of chemicals. In 2016, President Obama signed a revised TSCA that discourages testing conducted on vertebrate animals and requires the EPA to keep a database of validated alternative testing methods, taking a step forward in the US movement to eliminate animal testing.
The Consumer Product Safety Commission (CPSC) is charged with preventing injuries from consumer products. The CPSC enforces safety labeling regulations for such products as household cleaners, laundry detergents, fabric softeners, office products, and toys under the Federal Hazardous Substances Act (FHSA). This law requires that a manufacturer determine if a product should be labeled "harmful or fatal if swallowed" or "is a skin or eye irritant." For decades, rabbits have been most used in these sensitivity and irritation tests. Unlike humans and some other animals, rabbits do not have tear ducts, which means they cannot "cry out" chemicals applied directly to their eyes and are forced to suffer longer.
The CPSC also administers the Flammable Fabrics Act, which authorizes regulation of all flammable materials, including upholstery, pajamas, and other apparel. Industry laboratories conduct animal testing to determine the toxicity of substances applied to fabric in order to reduce or eliminate flammability.
The Occupational Safety and Health Administration (OSHA) governs worker health and safety and ensures that workers are protected from harmful levels of chemicals in the workplace. An estimated 190,000 illnesses and 50,000 deaths occur among U.S. workers exposed to chemicals, and OSHA hopes to replace these chemicals with safer alternatives. Currently, most of the information for OSHA's health and safety guidelines comes from research on animals.
What You Can Do


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There were a lot of highlights at the 2012 edition of The Headies held at the Expo hall of the Eko Hotels and Suits last Saturday but one that has got everyone talking is centered around act Burna Boy who fell off the stage as he was about perform. He however got back on stage and delivered a befitting performance with the help of Dammy Krane who later performed his single My Dear.
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LOL, The dude laughin in the background makes the fall look so funny….
R sure burna boy wasn't on smthn
being a super star does not make you super human, he falls on stage so what, at least he got back on his feet………………………………………. stop throwing stones at the poor guy…n give him a break
Yeah dats watsup…. Dats wat happens when a singer thinks he can as well be an orator… Tho he's my home boy!
D fall makes it fun tho…..his my manest man
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Kolkata: The Board of Control for Cricket in India (BCCI) on Friday decided to call an emergency general meeting (EGM) on December 25 to discuss the 'final offer' from International Cricket Council (ICC) to resolve the contracts issue. A hurriedly-called meeting of the office-bearers of BCCI felt that the final decision in this regard should be taken by the EGM. ICC had on Thursday made its final offer, granting a series of concessions in the original contracts clause to enable India to send its best team to the next year's World Cup. ICC said India should either accept this offer and send its best team to the World Cup or face the prospect of being penalised for non-fulfilment of its commitments under the Participating Nations Agreement.
BCCI convenes meet to decide on ICC contract issue


text: Hello wonderful wedding guests! Originally we weren't going to register because we were "non-traditional" and "above that materialism". However, a recent get-together with friends was a serious wake up call. We took a hard look into our cupboards and realized we didn't have any glasses. No, really. Not a single glass. We have been drinking everything out of mugs ever since Ed and Katie moved out. So, in the end, we decided to register. We also registered for experiences, because we feel strongly that experiences will stay with us forever and are more meaningful than material things (but seriously we need glasses). We love each other and each and every one of you, and are so excited to be sharing our happy union with you!


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Circa 1900 French Linen Factory Short Bath Cabinet
- No Longer Available -
A pair of metal cabinets built circa 1900 for a linen factory in the north of France inspired our careful reproduction – from the screened doors that allow airflow to treasured linens to the original hasp-and-staple hardware.
Show Details +
- 16"W x 16½"D x 34"H
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Hi, I have a scar in the center of my cornea (right eye only). I sometime wonder how soon does a cornea scar heal especially when it's not thick (a very thin one according to my doctors-1 mo. old). Is it really possible that it will vanish overtime? I'm 30 years old and everything's healthy and normal except for this scar. Thickness of my cornea was normal and even the topography. I'm having PredForte 4x/day and Vigamox 2x/day and Duotrav and Maxitrol before I sleep.
Thin Scar on My Cornea?
Doctor Answers 3
Do corneal scars fade?
Ulcers and trauma to the cornea can sometimes form scars if they penetrate beyond the layers of the epithelium. These scars will most likely be permanent since the inner layers of the cornea do not recycle like the outer epithelial layer. These superficial scars are generally not a problem for LASIK unless they are very thick and very deep, in which case they could affect the creation of the flap.
Since PRK treats the underlying Bowman's layers as well as the outer layers of the stroma, PRK can remove these scars but has a longer healing time than LASIK. If the scars do not affect vision, most surgeons will not change treatments in order to be rid of a scar that has no effect on visual performance.
Corneal scar
Corneal scars, just like any other scars on your body, may not disappear completely. They may somewhat fade over time. The location and the cause of the scar are the determining factors in what your vision will be once everything heals.
Scar on cornea
Stop the antibiotics you're not iinfected. It may resolve with steroids. If not a LASEK not LASIK would remove it and get rid of your prescription simultaneously
You might also like...
These answers are for educational purposes and should not be relied upon as a substitute for medical advice you may receive from your physician. If you have a medical emergency, please call 911. These answers do not constitute or initiate a patient/doctor relationship.


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If an item you ordered from TextbookRush does not meet your expectations due to an error on our part, simply fill out a return request and then return it by mail within 30 days of ordering it for a full refund of item cost.
Learn more about our returns policy
Description: This 44th edition—part of a series continuously published for more than 80 years and based on the 2014 National Electrical Code—is a handy instruction manual that has been used by generations of readers who learn the "why" as well as the "how-to" of wiring practices. Encouraging readers to tackle jobs small and large, the guide covers everything from repairing a table lamp to wiring a whole house. After introducing the basics—standards, codes, safety practices, and an overview of how electricity is measured and delivered—chapters show how to design a layout for lights, switches, and receptacles; run a line from a utility pole; install wires, circuits, and grounds; and handle special projects such as replacing old wiring and wiring detached garages and accessory buildings. The do-it-yourselfer appreciates the detailed instructions and drawings, the homeowner working with a contractor gains insight into how to communicate with the professional about the problems to be solved, and students and teachers appreciate the range and depth of the subject matter and the accompanying student workbook.
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Annual Report Finds Salaries Rise As Competition For Skilled Professionals Persists
MENLO PARK, CA -- Starting salaries for accounting and finance professionals are expected to increase an average of 4.3 percent in the coming year, according to the just-released 2008 Salary Guide from Robert Half. Public accountants, financial analysts and internal auditors are projected to see the largest gains.
Robert Half is the world's first and largest staffing services firm specializing in accounting and finance. Robert Half's financial staffing divisions include Accountemps®, Robert Half® Finance & Accounting and Robert Half® Management Resources, for temporary, full-time and senior-level project professionals, respectively. The 2008 Salary Guide is based on an analysis of the thousands of job placements managed by the company's U.S. offices.
"Competition for skilled financial professionals has prompted many companies to offer higher compensation to attract and retain top performers," said Max Messmer, chairman and CEO of Robert Half. "Employers seek staff who possess broad skill sets -- in addition to expertise in their functional areas. This includes information technology proficiency and strong communication abilities."
Not surprisingly, experienced candidates have greater leverage in negotiating compensation, and salaries for the most in-demand specialties are rising faster than the national average. Nationwide, demand is particularly strong among commercial construction, financial services and healthcare firms, Robert Half research shows.
Corporate Accounting: Salaries Rise for Analyst, Internal Audit Positions
Business expansion and ongoing corporate governance initiatives are fueling hiring among corporate accounting and finance departments. Entry-level financial, budget, treasury and cost analysts at large companies (more than $250 million in sales) are expected to see the biggest increases in base pay in 2008, with the average starting salary expected to rise 6.9 percent, to between $38,250 and $47,500 annually. Internal audit managers at large companies are forecast to receive starting compensation between $81,500 and $109,500 annually, an increase of
6.7 percent over last year's projections.
Public Accounting Outlook
Steady hiring is expected to continue in public accounting as firms seek staff to help deliver an expanding set of service offerings. Average starting salaries for senior managers and directors at midsize firms ($25 million to $250 million in sales) are projected to increase 7.7 percent in the year ahead, to between $88,250 and $129,250.
Professionals with one to three years of experience also are highly sought as firms look to address rising workloads and hire their next generation of leaders. At small firms (up to $25 million in sales), professionals at this stage of their careers can expect a 7.7 percent increase in average starting salaries, to a range of $44,750 to $53,250.
Banking and Financial Services Outlook
In 2008, commercial lenders with more than five years of experience can anticipate a 4.7 percent gain in starting salaries, to a range of $82,000 to $107,500. Average starting salaries for hedge fund accountants are expected to rise 6.5 percent, to between $46,250 and $64,500.
All salaries listed in the 2008 Salary Guide from Robert Half are national averages. Because hiring activity and compensation vary significantly by industry and geographic market, the Salary Guide includes a regional analysis of hiring trends and compensation variances for select U.S. markets.
Information in the guide is based on the thousands of job searches, negotiations and placements managed each year by Robert Half's staffing and recruiting managers. Continuing or ongoing salaries are not reported because many external factors -- such as seniority, work ethic, job performance and training -- impact the salaries of full-time professionals as work histories develop. For decades, companies have consulted the Salary Guide from Robert Half to determine appropriate compensation for all levels of accounting and finance professionals. In addition, the U.S. Department of Labor's Bureau of Labor Statistics references the guide when preparing its comprehensive Occupational Outlook Handbook.
Robert Half has more than 350 staffing locations in North America, South America, Europe and the Asia-Pacific region, and offers online job search services on its divisional websites, all of which can be accessed at www.roberthalf.com.


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Panoply 14845
- Brand: Panoply
- Style #: 14845 - Quick Delivery*
- Availability: In Stock
- $338
Like it's sister dress with the lace bell sleeve top, this style features the same matching rhinestones, sweetheart neckline, and beaded waistband; however, the bottom is a fabulous pair of bell bottom jersey pants. Lace, Jersey
Quick Delivery Items:
- Black: 0, 2, 4, 6, 8, 10
- Coral: 2, 4, 6, 8
*A style on our web site listed as in-stock can usually be shipped today or next day for immediate delivery or quick delivery. An item listed as "Ships Today" can be sent the same business day as long as the order is placed before the cutoff time.


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Neilla Banse
Services for Neilla Banse, 52, of Sutherland, will be held at 2 p.m., Saturday, Sept. 29, 2007, at United Methodist Church of Sutherland. Rev. Jud Stover will officiate the service.
Interment will take place at Harlan Cemetery in Dumont.
There will be no visitation.
Neilla passed away Wednesday, Sept. 19 at home.
Neilla Sue Banse, the daughter of Neil and Minnie (Winther) Harlan, was born March 14, 1945, in Hampton.ĀHer childhood years were spent in Dumont and Hampton where she graduated from Hampton High School. Neilla attended Iowa State Teacher's College and Buena Vista College where she received her teaching certificate.
On Sept. 23, 1966, Neilla was united in marriage to Eugene Banse in Newport, R.I.Ā Following their marriage Neilla traveled with her husband to Naval posts in Fall River, Mass., East Rumford, R.I., Vallejo, Calif., Great Lakes, Ill., Yokohama, Japan and Spanaway, Wash., returning to Iowa after Gene retired from the Navy.
During her time in Japan, Neilla taught English to the business community and gave the memorial speeches for the Americans intered in the Tokyo area.ĀShe was very active with the Japanese Girl Scout program.
Neilla was an assistant editor of the Sutherland Courrier for eight years and dearly loved the people that she came in contact with. Her joy was researching her family's historical lines. Neilla loved working with the youth: as a teacher; 35 years as a Girl Scout Leader, Council Member, Camp Coordinator and Area Director; over 20 years with the Boy Scouts; and as a coach for various girl's sport teams.
She was preceded in death by her parents; and brothers: Bruce and Michael Harlan.
Neilla is survived by her husband, Gene Banse of Sutherland; one son, Eric Banse of Anamosa; one daughter, Brandi Philbrick and her husband, Warren of Normal Ill.; two brothers:ĀDavid Harlan of Hampton, and Dwight Harlan and his wife, Mickey of Fertile; one sister, Georgia Hintz and her husband, John of Hampton; and seven grandchildren.
Warner Funeral Home of Sutherland is in charge of arrangements.


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- Sardian
- adjective or noun see Sardis
New Collegiate Dictionary. 2001.
New Collegiate Dictionary. 2001.
sardian — sar·di·an … English syllables
sardian — I. ˈsärdēən adjective Usage: usually capitalized Etymology: Latin sardianus, from Greek sardianos, from Sardeis Sardis, capital of the ancient kingdom of Lydia in Asia Minor 1. : of, relating to, or characteristic of the ancient city of Sardis in … Useful english dictionary
sardian nut — noun Usage: usually capitalized S : chestnut 1b … Useful english dictionary
Sardis — Sardian /sahr dee euhn/, n., adj. /sahr dis/, n. an ancient city in W Asia Minor: the capital of ancient Lydia. Also, Sardes /sahr deez/. Also called Tarne. * * * or Sardes Ancient city, Anatolia. Located east of Smyrna (modern İzmir), it was the … Universalium
Terisiare — In the fantasy trading card game , Terisiare was a large continent in the northern hemisphere of Dominaria. It is seen in several different times stretching several thousand years, with differing politics each time. It is at least the size of… … Wikipedia
Sard — Sard, n. [L. sarda, Gr. ?, or ? (sc. ?), i.e., Sardian stone, fr. ? Sardian, ? Sardes, the capital of Lydia: cf. F. sarde. Cf. {Sardius}.] (Min.) A variety of carnelian, of a rich reddish yellow or brownish red color. See the Note under… … The Collaborative International Dictionary of English
Chestnut — For other uses of chestnut , see Chestnut (disambiguation). For other uses of chinquapin or chinkapin , see Chinquapin (disambiguation). Chestnut Sweet Chestnut Castanea sativa Scientific clas … Wikipedia
RFactor — Infobox VG| title = rFactor developer = Image Space Incorporated publisher = Self published by Image Space Incorporated designer = Image Space Incorporated engine = gMotor2 released = release date and age|2005|8|31 latest release version = v1255… … Wikipedia
Sardis — or Sardes geographical name ancient city W Asia Minor capital of Lydia; site E of Izmir • Sardian adjective or noun … New Collegiate Dictionary
Eugenio Tavolara — (1901 ndash;1963) was an artist born in Sassari, Sardinia, Italy, with interests in many disciplines. He is well known for his hand crafted toys , most prominently small statues in terracotta representing Sardinians in traditional costumes.cite… … Wikipedia


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'We feel there is huge audience of Americans looking for legal alternatives to offshore sites', explained Alan Miller founder of NLOP. 'While offshore sites claim to offer 'free' poker, most also offer little to win. With NLOP, people can win huge prizes, and because we limit the amount of points they get to play with each day-the NLOP poker experience is more realistic than other free sites'.
Miller continued, 'Poker has exploded on TV, but US advertisers and sponsors have not been able to connect with the online poker audience'. There has been substantial precedent set for media and brand properties to stay far away from these offshore operators, NLOP provides advertisers and sponsors the opportunity to connect with the burgeoning poker demographic in a US-legal and fun fashion'.


text:
Harness Detail Lace Bralet Black-16
30,00 €
We're going crazy for the harness detail this season. Seriously sexy, it can instantly transform any outfit to something a little saucier. Wear with a bodycon-tagious black midi skirt and killer heels to finish this look and ensure all eyes are on you.
Approx length 34cm/13.5" (Based on a UK size 8 sample)
92% Polyester 8% Elastane
Lisa Marie wears a UK size 8/ EU size 36/ US size 4 and her height is 5'9"
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People who live in Hattiesburg and the greater Southern Mississippi area have enjoyed the unique flavor of Strick's BBQ for over 35 years. Family owned and operated, we strive to bring you authentic, home-cooked meals throughout the year. Our barbeque lunch buffet is legendary with crowds of folks flocking to the restaurant, others calling in for pickup orders, or companies order their office's lunches. So come on in and join us!
We offer dine-in and take out orders throughout the day for any of our items. Place your order at the counter and take a seat wherever you like. If you would like to take it to-go, drop in anytime to place your order, and we'll have it ready in just a few minutes.
In recent years Strick's has been getting requests to have items from their barbeque menu shipped all over the United States. We are now able to handle those shipping requests without sacrificing their slow cooked, smoked quality. We ship many of our menu items coast-to-coast in special containers right to your front door. You can choose from barbecue ribs, barbecue chicken, smoked drumettes, or our special barbeque sauces. Just give us a call and speak with Ken, our shipping manager, for more details.
We have a long history of successfully catering many events throughout South Mississippi. They can cater events for as few as 50 people up to 10,000! You pick the menu, and we do the work. We also cater more formal events, such as weddings. Let us know what we can do to make your party or special event a success. Click on the "Catering" button for more details and to check out some of the catering event photos.
We offers a private dining facility that can seat nearly 100 people. Your party can enjoy a private barbeque buffet or order from the counter. Just call or contact us for special pricing for your next business meeting, birthday party or holiday gathering.


text: I am trying to import smilies using an XML file created using this script - https://xenforo.com/community/threads/vbulletin-smilies-to-xml-conversion-script.50233/ I moved all the smilies into the correct file path on my server, but when I try to import the smilies using the XML file I get the following: Error: The provided file is not valid smilies XML. Has the format changed for the smilies XML? This is an example of what I have in my XML file Code: <?xml version="1.0" encoding="UTF-8"?> <smilies> <smilie> <title>1eye</title> <image_url>styles/flatawesome/xenforo/smilies/1eye.gif</image_url> <smilie_text>:1eye:</smilie_text> </smilie> ***other smilie data*** </smilies>


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Car Next Door lets you rent your neighbour's vehicle from $5 an hour or $25 a day, fully insured.
Reid Street, Fitzroy North VIC
Owner: Jacintho
Transmission: Automatic
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Daily Rate: $30.00
Rate per km: $0.33 (includes fuel)
Handy, popular car. Easy to drive, easy to get around. Spacious boot for a hatch.
84 Total tripsFeatures


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March 19, 2014
Lauren Mellor is a South African model who is also a rookie in this year's edition of Sports Illustrated Swimsuit Issue.
She was born in December 1985 and was a former "plus/healthy" sized model and has lost a bit of weight in recent years and now comes in at a still healthy 34E-25-36 frame.
16 more photos below…


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- Another in a long line of standout quarterbacks to emerge from the
Mid-American Conference in recent years, Frye is primed to follow in the footsteps of Marshall's Chad Pennington (New York Jets) and Byron Leftwich (Jacksonville) and Miami of Ohio's Ben Roethlisberger
- All-America Dream Team selection and the MAC's top player (Verne Smith
Leadership Award)
as a senior.
- Only the third quarterback in MAC history and the 16th in NCAA Division I-A
history to throw
for at least 2,000 yards in four consecutive seasons.
- His 11,049 passing yards rank third in MAC history and 15th in NCAA DI-A
- Frye will become just the 17th player from Akron to play in the NFL since
- He is the highest-drafted player from Akron since the AFL-NFL merger.
Previously, the highestdrafted
Zip was Miami Pro Bowl defensive end Jason Taylor, who was taken 73rd overall by the
Dolphins in 1997.
- The last player selected from the school was receiver Jake Schifino, who was
taken by the Titans
in the fifth round (151st overall) in 2002.
- Frye is the first player drafted by the Browns from Akron since tackle John Buddenberg was
selected in the 10th round of the 1989 draft. Prior to that, the most recent Akron selection by the
Browns was 16th round pick receiver Don Williams in 1967.
- Frye is seventh quarterback drafted by the Browns in the third round all-time.
Others include Eric
Zeier (Georgia, '95) and Mark Miller (Bowling Green, '78).
- Frye is the fourth quarterback drafted by the Browns in the team's new era.
The three others were
Luke McCown (fourth round, '04), Spergon Wynn (sixth round, '00) and Couch.