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© 2010 Frindik and Kemp, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.Biologics: Targets & Therapy 2010:4 147–155Biologics: Targets & TherapyDovepresssubmit your manuscript | www.dovepress.comDovepress 147 R e v i e wopen access to scientific and medical researchOpen Access Full Text ArticleManaging idiopathic short stature: role of somatropin (rDNA origin) for injection6363J Paul Frindik1Stephen F Kemp11University of Arkansas for Medical Sciences and Arkansas Children's Hospital, AR, USACorrespondence: Stephen F Kemp University of Arkansas for Medical Sciences, Department of Pediatrics, 1 Children's way, Little Rock, AR 72202, USA Tel +1 501 264 1430 Fax +1 501 364 6299 email firstname.lastname@example.com: Idiopathic short stature (ISS) is a term that describes short stature in children who do not have growth hormone (GH) deficiency and in whom the etiology of the short stature is not identified. Between 1985 and 2000, more than 40 studies were published regarding GH therapy for ISS. Only 12 of these had data to adult height, of which only 4 were controlled studies. A subsequent placebo-controlled study that followed subjects to adult height indicated that there was a gain of 3.7–7.5 cm in height with GH treatment. In 2003, the US Federal Drug Administration (FDA) approved GH for treatment of short stature. Even before FDA approval, patients with ISS made up about 20% of patients in GH databases, which is largely unchanged since FDA approval. There remains some controversy as to whether GH should be used to treat ISS. This controversy centers on the fact that there has been no definitive demonstration that short stature results in a disadvantage or problems with psychological adjustment, and thus, no demonstration that GH therapy results in improvement in quality of life.Keywords: idiopathic short stature, ISS, growth hormone therapy, somatotropin, somatropin, insulin-like growth factor I, IGF-1IntroductionIdiopathic short stature (ISS) is one of several terms that have been used to describe short stature in children who do not have growth hormone (GH) deficiency and in whom the etiology of their condition is not understood. Other terms that have been used in the past to describe these children, some overlapping those that describe ISS, include familial short stature, normal variant short stature, idiopathic growth failure, non-GH-deficient short stature, and nonendocrine short stature. Some patients with ISS have been diagnosed with GH neurosecretory dysfunction (ie, low spontaneous GH secretion) as a means of justifying GH therapy. All recognizable causes of short stature (ie, intrauterine growth retardation, genetic or syndromic causes of short stature, and psychosocial deprivation) should be ruled out before a diagnosis of ISS is made.1 As a group, children with ISS do not achieve their adult height predictions, and many have adult heights that are quite short.2,3 As more is understood about the causes of short stature, it is hoped that many of these children may eventually have a more definitive diagnosis. An example of this situ-ation is a recent report of a child with ISS who was ultimately diagnosed with a deletion in exon 5 of the Short Homeobox X (SHOX) gene.4A short history of GH therapyThe first report on GH therapy for growth hormone deficiency (GHD) was produced in 1958.5 The first GH preparations (somatotropin) used therapeutically were derived Number of times this article has been viewedThis article was published in the following Dove Press journal: Biologics: Targets & Therapy4 June 2010
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Biologics: Targets & Therapy 2010:4submit your manuscript | www.dovepress.comDovepress Dovepress148Frindik and Kempfrom human cadaver pituitaries. In the United States, human-derived growth hormone was produced and distributed by the National Institute of Health's (NIH) National Pituitary Agency. The preparation was in short supply, resulting in lower than ideal dosing and frequent drug holidays. Potential recipients were required to participate in a research protocol and, in order to ration the cadaveric GH, the diagnosis of GH-deficiency required that the patient have a peak GH level in response to provocative stimuli below a certain level. This requirement gradually increased in response to a better sup-ply of cadaveric GH, starting at 5 ng/mL, then 7 ng/mL, and finally 10 ng/mL in the early 1980s. In 1985, this preparation was linked to a risk for Creuzfeldt-Jacob disease,6,7 and its use was discontinued. In 1979, GH was produced in large quantities by expressing the human GH gene in Escherichia coli.8 In 1985, Genentech Inc. (San Francisco, CA, USA) was approved by the Food and Drug Administration (FDA) to market recombinant human growth hormone (rhGH),9 which was identical to human growth hormone, with the addition of a methionine as a necessary start signal for the bacteria to initiate protein synthesis. Use of methionyl GH did result in antibody production, but this was rarely associated with growth attenuation.10 Present-day commercial preparations (somatropin) all have the identical 191-amino acid sequence of native human pituitary hormone.11Initially, GH was injected intramuscularly. But, in the mid-1980s (about the time of introduction of rhGH), it was shown to be as effective if given as a subcutaneous injection,12 which is the practice today. Early in its use, GH was given twice weekly, but this was increased to three times weekly when the higher frequency was shown to result in an increased growth response.13 At about the time of the transition from cadaveric GH to rhGH, it was demonstrated that daily injections (6 or 7 per week) yielded an even better growth response than the three times per week schedule,14–17 and daily administration is commonly used today.GH treatment of ISSDuring the time of cadaveric growth hormone, usage was limited to GHD because of the scarcity of supply. However, even before the advent of rhGH, there was interest in investi-gating whether treatment of other conditions associated with short stature would increase adult stature. Between 1964 and 1971, there were a number of small studies that examined the treatment of non-GH-deficient short stature with GH.18 In 1964, the National Institute of Child Health and Human Development (NICHD), a branch of the NIH, sponsored an international conference that recommended analysis of GH treatment in non-GH-deficient conditions. In 1983, a conference s ponsored by the NICHD, entitled International Conference on Uses and Abuses of Growth Hormone, brought up this topic, resulting in the following statement: "… there is an urgent need for therapeutic trials to determine the effect of growth hormone in short children who do not have a growth hormone deficiency". In 1987, a FDA committee recom-mended a placebo-controlled study of GH treatment for ISS that would follow subjects to adult height.A placebo-controlled trial of treatment of children with ISS in collaboration with Eli Lilly (Indianapolis, IN, USA) and the NIH was carried out between 1988 and 2001. Data from this trial were presented to the NIH. In July 2003, the FDA approved the use of GH in children with ISS. They defined children with ISS as those having a height that was greater than 2.25 standard deviations (SD) below the mean (one of the inclusion criteria of the Eli Lilly/NIH collabora-tive trial), open epiphyses, a growth velocity that makes it unlikely that the child's adult height will be in the normal range (ie, within 2 SD of the mean), and a diagnostic evalu-ation that has excluded other causes associated with short stature, which would better be managed by observation or treatment by other means. One of the concerns has been the possibility of misdiagnosing and treating children for ISS who actually have constitutional delay in growth and matu-ration (CD), particularly if the child's bone age is delayed. Certainly, there are such patients. However, if the FDA guidelines are adhered to, a child who is more than 2.25 SD below the mean, and has a predicted adult height that is more than 2 SD below the mean, is probably more appropriately considered to have ISS than to be classified as having CD. There is evidence that adult height tends to be overpredicted, particularly in boys.19According to a recent survey of pediatric endocrinologists, there is still not agreement as to whether or when children with ISS should be treated.20 Most of the respondents to the survey agreed that there was a need for indication. Respondents were asked about the cut-off height of -2.25 SD. 71% responded that it was appropriate, 21% thought it should be set higher, and 8% thought it should be set lower. When asked about factors contributing to willingness to prescribe (78% selected more than one response), 53% selected "patient expression of understanding potential risk and benefits", 32% selected "family insistence", 14% selected "family's desire to pay", and 7% selected "male gender". The case against treatment is that there is not a convincing body of evidence to indicate that short stature is actually a real problem, or that treatment (or taller stature) leads to any psychological benefit.21 Treatment of
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Biologics: Targets & Therapy 2010:4submit your manuscript | www.dovepress.comDovepress Dovepress149 GH therapy of iSSGHD is justified because it represents replacement of a miss-ing hormone. On the side of treating ISS patients, Saenger22 argues that the diagnosis of GHD is very difficult to make with certainty, and in the absence of meaning psychological outcome data, we should follow the recommendation of the American Academy of Pediatrics,23 which recommends treat-ment of very short children whose ability to participate in basic activities of daily living is limited because of their short stature. One of the fears after ISS became an FDA-approved indication was that there would be a change in the paradigm determining which short children are treated (resulting in the treatment of many more children who were not as short). We compared demographic data in the National Cooperative Growth Study (NCGS) of children who were treated for ISS before 2003 and from 2003–2006 (ie, after FDA approval).24 Although no major changes were seen, there was a very small decrease in the severity of the growth retardation at entry, and a slight increase in the treatment doses. Mean height velocities during treatment were the same before and after FDA approval.Efficacy of GH treatment in ISSChildren with ISS who are treated with GH are as short at the beginning of GH therapy as children with chronic renal insufficiency, Turner syndrome, or those who are born small for gestational age: that is, their heights before treatment aver-age from -2.6 SD to -2.9 SD.25–29 In this group of children, insulin-like growth factor-1 (IGF-1) levels are often normal. However, approximately 25% of them are low, suggesting that some children in this group may have GH-insensitivity. Many of the published studies of GH therapy in children with ISS have involved small sample sizes and did not have control groups (28 uncontrolled vs 10 with a control group).18 Even with these limitations, a meta-analysis of these studies suggested that the overall height gain may have been from -3.0 to -1.5 SD with GH therapy,18 which represents a height increase of 4–6 cm. In studies with a control group, it appeared that the control group also had an increase in height (consistent with a previous report of spontaneous growth in children with ISS),30 but the treated group exceeded the control group by approximately 0.78 SD. Subsequent to this meta-analysis, results of a placebo-controlled study on the effect of GH therapy on adult height in peripubertal children with ISS demonstrated a height increase of 3.7–5.0 cm with GH therapy, despite a low dose of GH (0.22 mg/kg/week) and an injection schedule of three times per week.31 A second study evaluating two treatment protocols demonstrated a dose effect with a dosage of 0.37 mg/kg/week resulting in an increase in adult height of 7.2 cm compared with 5.4 cm in the group receiving only 0.24 mg/kg/week.32 A recent report of comparison of two doses (0.23 and 0.47 mg/kg/week) of GH and an untreated population in a group of 177 children, most of whom had ISS, showed that there was a dose-dependent increase in adult height,33 with a gain of about 1.5 SD in the group treated with the higher dose. An evaluation of data from children with ISS treated with GH, taken from a large GH database, showed that GH treatment resulted in an increase in height from -3.0 to -1.2 SD over the course of 7 years.26 Factors that tend to predict a posi-tive response to GH treatment include GH dose, degree of height deficit compared to parents' heights, young age, and first year height velocity.1,34Safety of GH treatment in ISSAn evaluation by Quigley et al35 of safety data from the controlled trial of GH therapy of children with ISS31 and the subsequent dose-response study,32 as well as an evaluation of more than 8,000 ISS patients followed in a large post-marketing database for children treated with GH,26 have shown that there are no safety issues in GH therapy different from those seen with treatment of GH deficiency.Psychosocial effect of treating ISSIt is assumed that short stature is associated with disadvan-tages and problems of psychological adjustment. Anecdotal reports include teasing, treating children in relation to their height rather than their age (juvenilization), and academic underachievement.36 Some studies seem to confirm these notions,37–40 while others have failed to demonstrate any disadvantage to short stature, including any problem with psychological adjustment.41–44 In fact, Kranzler et al45 evaluated 90 children who were sent to a stature clinic, and determined that they had normal psychological function without externalizing behavior problems, attention problems, or poor social skills, as had been previous reported.39,46,47 Sandberg48 reported that juvenilization does occur, but short stature is not associated with any social advantage. Balen et al49 have suggested that patients referred for ISS seem to be more at risk for psychological problems than those who are not referred. Further, they indicate that, in addition to stature, there are other risk factors for psychological diffi-culty, including being juvenilized, being a boy, having low intelligence, having a younger but taller sibling, and being part of a family with low socioeconomic status. In light of this controversy, it is not surprising that it has been diffi-cult to demonstrate that treatment of ISS (and short stature
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Biologics: Targets & Therapy 2010:4submit your manuscript | www.dovepress.comDovepress Dovepress150Frindik and Kempin general) improves the quality of life of the individual. Many who treat children with ISS believe that by increasing adult height they are improving quality of life.50 However, there is little objective data to support this notion.51 In fact, the idea that short stature is a problem that can be addressed by GH treatment has been recently challenged in the popular press.52 Recent reviews of available instruments for evalu-ating quality of life in children with GHD or ISS suggest that it should be possible to do the studies that could help answer whether treatment with GH has a positive or negative effect on quality of life.53,54 The question of efficacy of GH treatment is particularly relevant because of the expense of GH therapy: perhaps as much as US$52,634 per inch.55 In spite of the difficulty of demonstrating that an increase in height also results in increased quality of life, children with ISS have been treated with GH since at least the inception of the NCGS in 1985, accounting for approximately 20% of those patients treated with GH.56 Savage57 has suggested that 1) if growth hormone therapy is restricted to a height threshold of -2.5 or -3.0 SD, and 2) if treatment would be limited to those children with slow height velocity, there might be fewer children who would experience a benefit in terms of taller stature than would have been attained without treatment. Further, Savage indicates that continued treatment should depend upon an increase in height velocity of at least 2 cm/year; if such an increase in height velocity does not occur, GH therapy should be discontinued.Evidence that some ISS cases may be caused by genetic mutations in GH-IGF-1 axisThe GH receptor gene is the first gene that was associated with growth failure, possibly including ISS. It is well rec-ognized that mutations in the GH receptor are responsible for complete GH-resistance (also known as GH-insensitivity syndrome), in which it has been possible to identify about 70%–80% of patients with low levels of GH binding pro-tein (GHBP), which is the extracellular portion of the GH receptor. About 30 distinct mutations have been described.58 Point mutations of the intracellular domain have also been described. However, most of these have also been found in subjects with normal height, and have been considered to be polymorphisms.59–61 In order to determine whether partial GH-insensitivity was responsible for growth failure in children with ISS, data were analyzed from 773 children who were being treated with GH and were enrolled in a post-marketing surveillance project, the NCGS.62 Patients enrolled in this study had their levels of insuline-like growth factor 1 (IGF-1) and GHBP determined. In addition, these patients had been evaluated for GH-deficiency by their response to provocative stimuli. Patients with a GH response of more than 10 ng/mL were classified as having ISS. Children with ISS had GHBP levels more than 2 SD below the normal control patients, IGF-1 levels lower than controls (108–120 µg/L vs 217–308 µg/L), but higher than in patients with GH-deficiency (84–99 µg/L), and mean 12 hour GH concentra-tions similar to controls (2.2 µg/L vs 2.1–2.7 µg/L), but higher than in patients with GH-deficiency (1.2–1.4 µg/L). A subset of 14 of these patients (height more than 2.5 SD below mean, normal GH secretion, IGF-1 levels more than 2 SD below the mean, and serum concentrations of GHBP more than 2 SD below the mean) were further studied.63 Of the 14 patients, four had mutations in the GH receptor (none of the 24 control subjects had mutations). One of these patients was a compound heterozygote with respect to the GH receptor. Due to these findings, it has been suggested that partial GH-insensitivity may be a cause of growth failure in some children with ISS. It may be possible that they would respond to GH at higher doses, or it may be that these children should be treated with IGF-1 instead of GH. Certainly, the case can be made that mutations in the GH receptor could explain ISS in some of the patients. In a recent study, a pool of 188 patients with ISS were analyzed for mutations in the GH receptor in order to determine if finding these mutations would predict response to therapy. Mutations were present in fewer than 5% of the patients, and discovery of single-gene defects did not predict treatment response.64A second area of inquiry has been the SHOX gene. This gene resides on the distal ends of the short arms of chromo-somes X and Y (in the pseudoautosomal region).65 It appears that two functional copies of this gene are required for attain-ment of normal stature. Thus, absence of this gene from the loss of one or part of one X chromosome is associated with the short stature of Turner syndrome. Likewise, a mutation in one of the SHOX genes has been shown to be the cause of Leri-Weill syndrome, also known as dyschondrosteosis.66,67 Screening of ISS patients for abnormalities in the SHOX gene has been a logical step. Rao65 reported one patient with a functionally significant mutation in the SHOX gene out of 91 patients with ISS screened. Ogata68 expanded the screen to include 400 patients with ISS, and found the aforementioned patient, along with 3 others with SHOX gene mutations. In an analysis of 68 patients with ISS, one female patient was identified who had a normal karyotype but a deletion of one SHOX allele.69
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Biologics: Targets & Therapy 2010:4submit your manuscript | www.dovepress.comDovepress Dovepress151 GH therapy of iSSOther gene defects that have recently been discovered to result in growth failure include defects in the growth hor-mone receptor's intracellular signaling, in particular, signal transducer and activator of transcription 5b (STAT5b),70 and a defect in the acid-labile subunit (ALS) of the circulating IGF-1 complex.71 STAT5b-deficiency results in a phenotype of GH-insensitivity and immunodeficiency, while ALS-deficient patients have rather subtle growth failure, with height tracking at about or just below the 3rd centile. Neither of these defects has been identified in patients diagnosed as having ISS,64,72 perhaps in part because they represent very rare disorders. Also, it has been pointed out that the phenotype of STAT5b-deficiency is that of severe GH-resistance, and it is not likely to be mistaken for ISS.64 Perhaps the reason that ALS-deficiency has not been identified in a population of ISS patients is because the growth failure associated with it is too subtle for the affected child to be labeled as having ISS.It appears that mutations in the GH receptor and the SHOX gene account for between 1% and 5% of the cases of growth failure that are designated ISS. As more patients with ISS are investigated, it is likely that additional genes responsible for growth failure will be discovered. As we recognize various causes for ISS, the pool of children with this designation should continue to decrease.IGF-1 treatment of ISSIn August and December of 2005, mecasermin IGF-1 (Increlex®, Tercica Inc, Brisbane, CA, USA) and mecaser-min rinfabate IGFBP-3 (Insulin-like growth factor binding protein 3) (Iplex®, Insmed, Glen Allen, VA, USA) received approval from the FDA for the treatment of children with severe primary IGF-deficiency or children with a GH gene deletion who have developed neutralizing antibodies to GH. Mecasermin rinfabate is no longer available for treating con-ditions with short stature because of a legal agreement. These compounds have been shown to be effective in treating cases of GH-insensitivity73,74 and IGF gene deletion.75 In spite of ISS being an off-label use, there was a poster presentation of data from the Increlex Growth Forum Database Registry at the 2007 meeting of the Endocrine Society,76 which showed that 17% of enrolled patients were identified as having ISS. Rosenbloom77 has assented that "partial GH-insensitivity" is not evidence-based, but represents an attempt by the manufacturer to promote use of their product by a wider market than the rather small number of patients with true GH-insensitivity.77 Because of the paucity of published data regarding the treatment of ISS (or partial GH-insensitivity), the role of treatment of ISS with IGF-1 remains to be determined.78,79Treatment of GH receptor-deficiency with IGF-1 has resulted in a number of mild to moderate adverse events. Most commonly reported adverse events have included pain at the injection site and headaches. Data from a European study indicate that these events occur during the first month of treatment and then improve.80 Other adverse events that have been reported following IGF-1 therapy have included lipohypertrophy at the injection site, papil-loedema related to increased intracranial hypertension, and facial nerve paralysis.81,82 With these events, symptoms resolved after interrupting treatment and re-starting with a lower dose.80,83A second concern has been hypoglycemia, which occurred in some of the patients receiving IGF-1, but only rarely resulted in seizures.73,84 This problem was lessened by administering the IGF-1 dose with meals, and hypoglycemia was usually a problem when there was an intercurrent illness resulting in loss of appetite.Another effect of IGF-1 therapy has been the growth of lymphoid tissue, in particular, splenic enlargement and tonsillar hypertrophy. Renal size also increased, but renal function remained normal.73 There were changes in facial appearance, with coarsening of features and an increase in hair growth, which were most noticeable during puberty. A complex of IGF-1 and IGFBP-3 appears to prolong the half-life and might counteract acute adverse events, particularly hypoglycemia associated with administration of IGF-1.A recent report of treatment of 136 short children (pre-sumable ISS) with IGF-185 showed that there was a statisti-cally significantly increased growth velocity in the groups receiving 80 or 120 µg/kg twice daily vs a non-treated control group. However, there were significant reports of adverse events in the group: headaches 38%, vomiting 25%, and hypoglycemia 14%; in fact, six subjects withdrew because of adverse events. In an accompanying editorial, Rosenbloom and Rivkees86 question whether there is adequate growth promotion to justify the apparent risks of treating with IGF-1 in this population.Other approaches to treatment of ISSLHRH agonistsIt is well-recognized that treatment of early-onset preco-cious puberty with luteinizing hormone-releasing hormone (LHRH) agonists such as gonadotropin-releasing hormone agonist (GnRHa) allows adult height to approach target height.87 It has been postulated that GH may hasten the
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Biologics: Targets & Therapy 2010:4submit your manuscript | www.dovepress.comDovepress Dovepress152Frindik and Kemp progression of puberty, and that the addition of GnRHa treatment may permit further growth in children with ISS. Kamp et al demonstrated that the addition of GnRHa to GH therapy in children with ISS or intrauterine growth restriction resulted in an increase in predicted adult height of 8.0 cm in girls and 10.4 cm in boys.88 A prospective study comparing treatment of normal short girls with GH alone or with GH plus GnRHa suggested that while GH alone resulted in an increase in predicted adult height, the addition of GnRHa combined with GH resulted in an even greater increase in predicted adult height.89 The evaluation of two large GH registry databases,90 GH prediction models,90 and a recent report of lack of efficancy in increasing adult height when treatment is initiated after the age of 7–8 years91 do not sup-port the success of this treatment. At present, there are no universally agreed upon guidelines for the use of GnRHa with (or without) GH in children with ISS. Thus, this therapy is still considered experimental.Aromatase inhibitorsA recent study has demonstrated a 5.9 cm increase in pre-dicted adult height in boys with ISS using an inhibitor of aromatase (letrozole) without GH treatment for 24 months.92 The same group has reported a similar finding in boys with constitutional delay treated to near adult height with letrozole.93 The group receiving letrozole reached a near adult height which was 6.7 cm taller than those who did not. Although these reports appear quite promising, further studies carried out to adult height, with a careful evaluation of safety, are needed before this therapy can be adopted in a clinical setting.87ConclusionISS describes a group of children who are very short (more than 2 SD below the mean) and who are not GH-deficient. As early as 1983, there was interest in determining whether treating these children increased their adult height. Between 1985 and 2000, there were more than 40 studies published on the treatment of ISS. Most involved small patient popu-lations, only 12 had adult height data, and only four were controlled. A controlled study was undertaken between the NHI and Eli Lilly. Subsequently, that study demonstrated an increase in adult height from 3.7–7.5 cm (1.5–3 inches) with GH treatment.31,32 The FDA approved the ISS indication in July 2003. An analysis of the data from a large registry of patients receiving GH demonstrated a similar response to therapy and no differences in safety than for the treatment of GH-deficiency. Genetic explanations for ISS have occurred in approximately 5% of the patients evaluated, including genetic mutations of the GH-IGF-1 axis, including STAT5b mutations, SHOX gene mutations, and ALS mutations. With time, there will likely be a larger group of patients in which the etiology of their short stature is elucidated. There are few data regarding whether a psychological advantage is gained by patients with ISS treated with GH. Other approaches to treating ISS include treating with IGF-1 (alone or in combination with GH), which has the added risk of adverse events, or delaying puberty with LHRH agonists or aro-matase inhibitor. Both of the latter approaches are still in experimental stages.DisclosuresThe authors reports no conflicts of interest in this work.References 1. Wit JM, Clayton PE, Rogol AD, Savage MO, Saenger PH, Cohen P. Idiopathic short stature: definition, epidemiology, and diagnostic evalu-ation. Growth Horm IGF Rese. 2008;18(2):89–110. 2. Buchlis JG, Irizarry L, Crotzer BC, Shine BJ, Allen L, MacGillivray MH. Comparison of final heights of growth hormone-treated vs untreated children with idiopathic growth failure. J Clin Endocrinol Metab. 1998;83(4):1075–1079. 3. Ranke MB, Grauer ML, Kistner K, Blum WF, Wollmann HA. Spon-taneous adult height in idiopathic short stature. Hormone Rese. 1996;44(4):152–157. 4. Shanske AL, Puri M, Marshall B, Saenger P. Unique deletion in exon 5 of SHOX gene in a patient wtih idiopathic short stature. Hormone Res. 1996;67(2):61–66. 5. Raben MS. Treatment of a pituitary dwarf with human growth hormone. J Clin Endocrinol Metab. 1958;18(8):901–903. 6. Frasier SD. The not-so-good old days: working with pituitary growth hormone in North America, 1956–1985. J Pediatr. 1997;131 (1 Pt 2):S1–S4. 7. Hintz RL. The prismatic case of Creutzfeldt-Jacob disease associated with primary growth hormone treatment. J Clin Endocrinol Metab. 1995;80(8):2298–2301. 8. Goeddel DV, Heyneker HL, Hozumi T, et al. Direct expression in Escherichia coli of a DNA sequence coding for human growth hormone. Nature. 1979;281(5732):544–548. 9. Flodh H. Human growth hormone produced with recombinant DNA technology: development and production. Acta Paediatr Scand Suppl. 1986;325:1–9. 10. Massa GG, Vanderschueren-Lodeweyckx M, Bouillon R. Five-year follow-up of growth hormone antibodies in growth hormone deficient children treated with recombinant human growth hormone. Clin Endo-crinol (Oxf). 1993;38(2):137–142. 11. Franklin SL, Geffner ME. Growth hormone: the expansion of avail-able products and indications. Endocrinol Metav Clin North Am. 2009;38(3):587–611. 12. Wilson DM, Baker B, Hintz RL, Rosenfeld RG. Subcutaneous versus intramuscular growth hormone therapy: growth and acute somatomedin response. Pediatrics 1985;76(3):361–364. 13. Milner RD, Russell-Fraser T, Brook CG, et al. Experience with human growth hormone in Great Britain: the report of the MRC Working Party. Clin Endocrinol (Oxf). 1979;11(1):15–38. 14. Albertsson-Wikland K, Westphal O, Westgren U. Daily subcutaneous administration of human growth hormone in growth hormone deficient children. Acta Paediatr Scand. 1986;75(1):89–97.
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Biologics: Targets & Therapy 2010:4submit your manuscript | www.dovepress.comDovepress Dovepress153 GH therapy of iSS 15. Jorgensen JO, Moller N, Laruritzen T, Alberti KG, Orskov H, Christiansen JS. Evening versus morning injections of growth hor-mone (GH) in GH-deficient patients: effects on 24-hour patterns of circulating hormones and metabolites. J Clin Endocrinol Metab. 1990;70(1):207–214. 16. Kastrup KW, Christiansen JS, Andersen JK, Orskov H. Increased growth rate following transfer to daily sc administration from three weekly im injections of hGH in growth hormone deficient children. Acta Endocrinol (Copenh). 1983;104(2):148–152. 17. MacGillivray MH, Baptista J, Johanson AJ. Outcome of a four-year randomized study of daily versus three times weekly soma-tropin treatment in prepubertal naive growth hormone-deficient children. Genentech Study Group. J Clin Endocrinol Metab. 1996;91(5):1806–1809. 18. Finkelstein BS, Imperiale TF, Speroff T, Marrero U, Radcliffe DJ, Cutler L. Effect of growth hormone therapy on height in children with idiopathic short stature: a meta-analysis. Arch Pediatr Adolesc Med. 2002;156(3):230–240. 19. Bramswig JH, Fasse M, Holthoff ML, von Lengerke HJ, von Petrykowski W, Schellong G. Adult height in boys and girls with untreated short stature and constitutional delay of growth and puberty: accuracy of five different methods of height predicition. J Pediatr. 1990;11(7):886–891. 20. Hardin DS, Woo J, Butsch R, Huett B. Current prescribing practices and opinions about growth hormone therapy: results of a nation-wide survey of paediatric endocrinologists. Clin Endocrinol (Oxf). 2007;66(1):85–94. 21. Voss LD. Growth hormone therapy for the short normal child: who needs it and who wants it. J Pediatr. 2000;136(1):103–106. 22. Saenger P. The case in support of GH therapy. J Pediatr. 2000;136(1): 106–109. 23. American Academy of Pediatrics Committee on Drugs and Com-mittee on Bioethics. Considerations related to the use of recombi-nant human growth hormone in children. Pediatrics. 1997;99(1): 122–129. 24. Kemp SF, Dana K, Frane J, Lippe B. Idiopathic Short Stature (ISS): What has changed since FDA approval of growth hormone (GH) for this diagnosis? Data from the Genentech (GNE) National Cooperative Growth Study (NCGS). Paper presented at: Annual Meeting of The Endocrine Society, 2007;Toronto, Canada. 25. Fine RN. Recombinant human growth hormone in children with chronic renal insufficiency – clinical update: 1995. Kid Int Suppl. 1996;53:S1115–S1118. 26. Kemp SF, Kuntzie J, Attie KM, et al. Efficacy and safety results of long-term growth hormone treatment of idiopathic short stature. J Clin Endocrinol Metab. 2005;90(9):5247–5253. 27. Ranke MB, Lindberg A, Chatelain P, et al. Prediction of long-term response to recombinant human growth hormone in Turner syndrome: development and validation of mathematical models. KIGS Interna-tional Board. Kabi International Growth Study. J Clin Endocrinol Metab. 2000;85(11):4212–4218. 28. Ranke MB, Lindberg A, Cowell CT, et al. Prediction of response to growth hormone treatment in short children born small for gestational age: analysis of data from KIGS (Pharmacia International Growth Database). J Clin Endocrinol Metab. 2003;88(1):125–131. 29. Root AW, Kemp SF, Rundle AC, Dana K, Attie KM. Effect of long-term recombinant growth hormone therapy in children National Coopera-tive Growth Study, USA, 1985–1994. J Pediatr Endocrinol Metabol. 1998;11:403–412. 30. Rekers-Mombarg LTM, Wit JM, Massa GG, et al. Spontaneous growth in idiopathic short stature. European Study Group. Arch Dis Child. 1996;75(3):175–180. 31. Leschek EW, Rose SR, Yanovski JA, et al. Effect of growth hormone treatment on adult height in peripubertal children with idiopathic short stature: a randomized, double-blind, placebo-controlled trial. J Clin Endocrinol Metab. 2004;89(7):3140–3148. 32. Wit JM, Rekers-Mombarg LTM, Cutler GB Jr, et al. Growth hormone (GH) treatment to final height in children with idiopathic short stature: evidence for a dose effect. J Pediatr. 2005;146(1):45–53. 33. Albertsson-Wikland K, Aronson AS, Gustafsson J, et al. Dose- dependent effect of growth hormone on final height in children with short stature without growth hormone deficiency. J Clin Endocrinol Metab. 2008;93(11):4342–4350. 34. Ranke MB, Lindberg A, Price DA, et al. Age at growth hormone therapy start and first-year responsiveness to growth hormone are major deter-minants of height outcome in idiopathic short stature. Hormone Rese. 2007;58(2):53–62. 35. Quigley CA, Gill AM, Crowe BJ, et al. Safety of growth hormone treatment in pediatric patients with idiopathic short stature. J Clin Endocrinol Metab. 2005;90(5):5188–5196. 36. Ross JL, Sandberg DE, Rose SR, et al. Psychological adaptation in children with idiopathic short stature treated with growth hormone or placebo. J Clin Endocrinol Metab. 2004;89(10):4873–4878. 37. Gordon M, Crouthamel C, Post EM, Richman RA. Psychological aspects of constitutional short stature: social competance, behavior problems, self-esteem, and family functioning. J Pediatr. 1982; 101:477–480. 38. Siegal PT, Clopper RR, Stabler B. Psychological impact of significantly short stature. Acta Paediatr Scand. 1991;377 Suppl:14–18. 39. Stabler B, Clopper RR, Siegal PT, Stoppani C, Compton PG, Under-wood LE. Academic achievement and psychological adjustment in short children: The National Cooperative Growth Study. J Dev Behav Pediatr. 1994;15:1–6. 40. Steinhausen HC, Dorr HG, Kannenberg R, Malin Z. The behavior profile of children and adolescents with short stature. J Dev Behav Pediatr. 2000;21:423–428. 41. Downie AB, Mulligan J, Stratford RJ, Betts PR, Voss LD. Are short normal children at a disadvantage? The Wessex growth study. BMJ. 1997;314(7074):97–100. 42. Skuse D, Gilmour J, Tian CS, Hindmarsh PC. Psychological assess-ment of children with short stature: a preliminary report. Acta Paediatr Scand. 1994;406 Suppl:11–16. 43. Voss LD. Short normal stature and psychological disadvantage: a critical review of the evidence. J Pediatr Endocrinol Metab. 2001; 14:701–711. 44. Voss LD, Bailey BJ, Mulligan J, Wilkin TJ, Betts PR. Short stature and school performance--the Wessex growth study. Acta Paediatr Scand. 1991;377 Suppl:29–31. 45. Kranzler JH, Rosenbloom AL, Proctor B, Diamond FB. Is short stature a handicap? A comparison of the psychosocial functioning of referred and nonreferred children with normal short stature and children with normal stature. J Pediatr. 2000;136(1):96–102. 46. Stabler B. Growth hormone insufficiency during childhood has implica-tions for later life. Acta Paediatr Scand. 1991;377 Suppl:9–13. 47. Underwood LE. The social cost of being short: societal perceptions and biases. Acta Paediatr Scand. 1991;377 Suppl:308. 48. Sandberg DE, Bukowski WM, Fung CM, Noll RB. Height and social adjustment: are extremes a cause for concern and action? Pediatrics. 2004;114(3):744–750. 49. Balen HV-v, Sinnema G, Geenen R. Growing up with idiopathic short stature: psychosocial development and hormone treatment: a critical review. Arch Dis Child. 2006;91:433–439. 50. Kemp SF. Height and social adjustment. Pediatrics. 2005;115(2):515. 51. Cohen P, Rogol AD, Deal CL, et al. Consensus statement on the diagnosis and treatment of children with idiopathic short stature: A summary of the Growth Hormone Research Society, the Lawson Wilkins Pediatric Endocrine Society, and the European Society for Paediatric Endocrinology workshop. J Clin Endocrinol Metab. 2008;93(11):4210–4217. 52. Cosgrove C, Cohen S. Normal at Any Cost: Tall Girls, Short Boys, and the Medical Industry's Quest to Manipulate Height. New York, NY: Penguin Group; 2009.
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Biologics: Targets & Therapy 2010:4submit your manuscript | www.dovepress.comDovepress Dovepress154Frindik and Kemp 53. Brutt AL, Sandberg DE, John C, et al. Assessment of helth-related quality of life and patient satisfaction in children and adolescents with growth hormone deficiency or idiopathic short stature – Part 1: A criti-cal evaluation of available tools. Hormone Rese. 2009; 72(2):65–73. 54. Bullinger M, Koltowska-Haggstrom M, Sandberg DE, et al. Health-related quality of life of children and adolescents with growth hormone deficiency or idiopathic short stature – Part 2: Available results and future directions. Hormone Rese. 2009;72(2):74–81. 55. Lee JM, Davis MM, Clark SJ, Hofer TP, Kemper AR. Estimated cost-effectiveness of growth hormone therapy for idiopathic short stature. Arch Pediatr Adolesc Med. 2006;160(3):263–269. 56. Kemp SF. Growth hormone treatment of idiopathic short stature: his-tory and demographic data from the NCGS. Growth Horm IGF Rese. 2005;15 Suppl A:S9–S12. 57. Savage MO. Should idiopathic short stature be treated with growth hormone? Nat Clin Pract Endocrinol Metab. 2009;5(3):148–149. 58. Woods KA, Clark AJ, Amselem S, Savage MO. Relationship between phenotype and genotype in growth hormone insensitivity syndrome. Acta Paediatr Suppl. 1999;88(428):158–162. 59. Goddard A, Dowd P, Chernausek SD, et al. Partial growth-hormone insensitivity: the role of growth-hormone receptor mutations in idio-pathic short stature. J Pediatr. 1997;131 Suppl:51–55. 60. Iida K, Takahashi Y, Kaji H, et al. The C422F mutation of the growth hormone receptor gene is not responsible for short stature. J Clin Endocrinol Metab. 1999;84(11):4214–4219. 61. Savage MO, Woods KA, Johnston LB, Postel-Vinay MC, Amselem S, Clark AJ. Defects of the growth hormone receptor and their clinical implications. Growth Horm IGF Rese. 1999; 9 Suppl A:57–61. 62. Attie KM, Carlsson LM, Chen Rundle A, Sherman B. Evidence for partial growth hormone insensitivity among patients with idiopathic short stature. J Pediatr. 1995;127(2):244–250. 63. Gollust SE, Thompson RE, Gooding HC, Biesecker BB. Living with achondroplasia in an average-sized world: an assessment of quality of life. Am J Med Genet. Part A. 2003; 120(4):447–458. 64. Savage MO, Camacho-Hübner C, David A, et al. Idiopathic short stat-ure: will genetics influence the choice between GH and IGF-1 therapy? Eur J Endocrinol. 2007;157 Suppl 1:S33–S37. 65. Rao E, Weiss B, Fukami M, et al. Pseudoautosomal deletions encom-passing a novel homeobox gene cause growth failure in idiopathic short stature and Turner syndrome. Nat Genet. 1997;16(1):54–63. 66. Belin V, Cusin V, Viot G, et al. SHOX mutations in dyschondrosteosis (Leri-Weill syndrome). Nat Genet. 1998;19(1):67–69. 67. Cormier-Daire V, Belin V, Cusin V, et al. SHOX gene mutations and deletions in dyschondrosteosis or Leri-Weill syndrome. Acta Paediatr Suppl. 1999;88(433):55–59. 68. Ogata T. SHOX: pseudoautosomal homeobox containing gene for short stature and dyschondrosteosis. Growth Horm IGF Rese. 1999;9 Suppl B:53–57. 69. Binder G, Schwarze CP, Ranke MB. Identification of short stature caused by SHOX defects and therapeutic effect of recombinant human growth hormone. J Clin Endocrinol Metab. 2000;85(1):245–249. 70. Kofoed EM, Hwa V , Little B, et al. Growth hormone insensitivity associ-ated with a STAT5b mutation. N Engl J Med. 2003;349:1139–1147. 71. Domene HM, Bengolea SV, Martinez AS, et al. Deficiency of the circulating insulin-like growth factor system associated with inac-tivation of the acid-labile subunit. N Engl J Med. 2004;350(6): 570–577. 72. Salerno M, Balestrieri B, Matrecano E, et al. Abnormal GH receptor signalling in children with idiopathic short stature. J Clin Endocrinol Metab. 2001;86:3882–3888. 73. Backeljauw PF, Underwood LE, Group TGC. Therapy for 6.5–7.5 years with recombinant insulin-like growth factor I in children wtih growth hormone insensitivity syndrome: a clinical research center study. J Clin Endocrinol Metab. 2001;86:15–14–1510. 74. Raynor K, Murphy W, Coy D, et al. Cloned SRIF receptors: identifica-tion of subtype selective peptides and demonstration of high affinity binding of linear peptides. Mole Pharmacolo. 1993; 43:838–844. 75. Camacho-Hubner C, Woods KA, Miraki-Moud F, et al. Effects of recombinant human insulin-like growth factor-I (IGF-1) therapy on the growth hormone-IGF system of a patient with a partial IGF-gene deletion. J Clin Endocrinol Metab. 1999;84:1611–1616. 76. Blethen SL, Hertz J, Kuntze J. The Increlex Growth Forum Database Registry: a Web-based patient registry for monitoring long-term safety and efficacy of Increlex treatment. Paper presented at: The Endocrine Society, 2007; Toronto, Canada. 77. Rosenbloom AL. Insulin-like growth factor-I (rhIGF-1) therapy of short stature. J Pediatr Endocrinol Metab. 2008;21:301–315. 78. Collett-Solberg PF, Misra M. The role of recombinant human insulin-like growth factor-I in treating children with short stature. J Clin Endocrinol Metab. 2008;93(1):10–18. 79. Richmond EJ, Rogol AD. Recombinant human insulin-like growth factor-I therapy for children with growth disorders. Adv Ther. 2008;25(12):1276–1287. 80. Ranke MB, Wollmann HA, Savage MO. Experience with insulin-like growth factor I (IGF-1) treatment of growth hormone insensitivity syndrome (GHIS). J Pediatr Endocrinolo Metab. 1999;12:259–266. 81. Clemmons DR, Moses AC, Sommer A, et al. Rh/IGF-1/rhIGFBP-3 administration to patients with type 2 diabetes mellitus reduces insulin requirements while also lowering fasting glucose. Growth Horm IGF Rese. 2005;15(4):265–274. 82. Quattrin T, Thrailkill KM, Baker L, et al. Dual hormonal replacement with insulin and recombinant human insulin-like growth factor I in IDDM. Effects on glycemic control, IGF-1 levels, and safety profile. Diabetes Care. 1997;20(3):374–380. 83. Chernausek SD, Backeljauw PF, Frane J, Kuntze J, Underwood LE, Group GISC. Long-term treatment with recombinant insulin-like growth factor (IGF-1) in children with severe IGF-1 deficiency due to growth hormone insensitivity. J Clin Endocrinol Metab. 2007; 92(3):902–910. 84. Guevara-Aguirre J, Vasconez O, Martinez V, et al. A randomized double-blinded placebo controlled trial on safety and efficacy of recombinant human insulin-like growth factor-I in children with growth hormone deficiency. J Clin Endocrinol Metab. 1995;80: 1393–1398. 85. Midyett LK, Rogol AD, Van Meter QL, Frane J, Bright GM. Recom-binant insulin-like growth factor (IGF)-I treatment in short children with low IGF-1 levels: first-year results from a randomized clinical trial. J Clin Endocrinol Metab. 2010;10(2):611–619. 86. Rosenbloom AL, Rivkees SA. Off-label use of recombinant IGF-1 to promote growth: is it appropriate? J Clin Endocrinol Metab. 2010; 95(2):505–508. 87. Wit JM, Balen HV, Kamp GA, Oostdijk W. Benefit of postpon-ing normal puberty for improving final height. Eur J Endocrinol. 2004;151:S41–S45. 88. Kamp GA, Mul D, Waelkens JJ, et al. A randomized controlled trial of three years' growth hormone and gonadotropin-releasing hormone agonist treatment in children with idiopathic short stat-ure and intrauterine growth retardation. J Clin Endocrinol Metab. 2001;86(7):2969–2975. 89. Pasquino AM, Pucarelli I, Roggini M, Segni M. Adult height in short normal adolescent girls treated with gonadotropin-releasing hormone analog and growth hormone. J Clin Endocrinol Metab. 2000;85(2):619–622. 90. Reiter EO. A brief review of the addition of gonadotropin-releasing hormone agonists (GnGH-ag) to growth hormone (GH) treatment of children with idiopathic growth hormone deficiency: previously pub-lished studies from America. Molecular and Cellular Endocrinology. 2006;254–255:221–225.
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Biologics: Targets & TherapyPublish your work in this journalBiologics: Targets & Therapy is an international, peer-reviewed journal focusing on the patho-physiological rationale for and clinical applica-tion of Biologic agents in the management of autoimmune diseases, cancers or other pathologies where a molecular target can be identified. This journal is indexed on PubMed Central, CAS, EMBase, Scopus Submit your manuscript here: http://www.dovepress.com/biologics-targets--therapy-journaland the Elsevier Bibliographic databases. The manuscript management system is completely online and includes a very quick and fair peer-review system, which is all easy to use. Visit http://www.dovepress.com/testimonials.php to read real quotes from published authors.Biologics: Targets & Therapy 2010:4submit your manuscript | www.dovepress.comDovepress DovepressDovepress155 GH therapy of iSS91. Magiakou MA, Manousaki D, Papadaki M, et al. The efficacy and safety of gonadotropin-releasing hormone analog treatment in childhood and adolescence: a single center, long-term follow-up study. J Clin Endocrinol Metab. 2010;95(1):109–117. 92. Hero M, Norjavaara E, Dunkel L. Inhibition of estrogen biosynthesis with a potent aromatase inhibitor increases predicted adult height in boys with idiopathic short stature: a randomized controlled trial. J Clin Endocrinol Metab. 2005;90(12):6396–6402. 93. Hero M, Wickman S, Dunkel L. Treatment with the aromatase inhibitor letrozole during adolescence increases near-final height in boys with constitutional delay of puberty. Clin Endocrinol (Oxf). 2006;64(5):510–513.


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Life Sciences Tools and Services
Company Overview of WaveSense, Inc.
BOARD MEMBERS AFFILIATED WITH Robert L. Coleman Ph.D.*
Founder and Director
MOST CONNECTED PEOPLE TO Robert L. Coleman Ph.D.
|Daniel J. Mitchell
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|Jack L. McGinley
|20 Relationships
Sponsored Financial Commentaries
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Only a company representative may request an update for the company profile. Documentation will be required.
To contact WaveSense, Inc., please visit . Company data is provided by Capital IQ. Please use this form to report any data issues.
Our data partners will research the update request and update the information on this page if necessary. Research and follow-up could take several weeks. If you have questions, you can contact them at firstname.lastname@example.com.

subset: commoncrawl


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Director Steven Soderbergh once shook things up in the film world by working with adult film star Sasha Grey for his experimental drama The Girlfriend Experience. The film followed the life of a call girl moving from client to client in New York City during the days leading up the 2008 presidential election. Show More Summary
Years in the making, Steven Soderbergh's TV version of his 2009 film, The Girlfriend Experience, is finally coming to Starz on April 10. While the film starred Sasha Grey as a very professional high-end call girl, the TV version follows Riley Keough as a law student who's just starting out in... More »
"The Girlfriend Experience" is a name that may sound familiar. In 2009, director Steven Soderbergh made a film by the same name that starred former adult film star Sasha Grey. The film followed a call girl and her attempts to juggleShow More Summary
Back in 2009, Soderbergh released THE GIRLFRIEND EXPERIENCE, a film starring Sasha Grey as an in-demand, high-priced call girl. Soderbergh will soon be bringing the series to Starz as an anthology show. THE GIRLFRIEND EXPERIENCE follows a woman named Christine Reade (Riley Keough), a second year law student who is also a new intern at […]
The former porn star is being dragged into a social media war between Russia and Ukraine, but whose side is she on?
Rumor: Porn star Sasha Grey was killed by Ukrainian military forces.
It's not every day that a former adult film star turned The Girlfriend Experience/Entourage actress becomes a part of what she… Read More
Grey is being used as a pawn in a propaganda war.
Sasha Grey has not died in Ukraine, despite some propaganda from Russian-backed militants that claimed the porn star died while volunteering as a nurse during the conflict. The group made posts on social media claiming that the popular American porn star was treating militants injured during the conflicts when she became a casualty herself. Show More Summary
Former porn star Sasha Grey would just like to make sure we're all clear on the fact that she's not dead. Contrary to the reports of some dicey-looking Internet memes, she also wasn't working as a nurse for the Russian Army, and has never—not even once—been captured by Ukrainian soldiers and then brutally murdered. She's fine. Read more...
Apparently she hasn't been moonlihgting as a nurse in Ukraine
Yesterday, actress and former porn star Sasha Grey took to Twitter to address rumors that she was brutally and horrifically murdered by Ukrainian soldiers while serving as a battlefield nurse in Eastern Ukraine. (She is not a nurse, nor is she dead.)
The Book of Life - For whatever reason, Fox was gung-ho about inviting me to various pre-release events to hype this uniquely Mexican-American animated feature, but less interested in making it ea...
by Jonathan Blaustein Have you ever heard of Sasha Grey? Maybe? Maybe not. As it happens, she's a young actress from California. I first saw her in Steven Soderbergh's taut little film, "The Girlfriend Experience." She is lithe, Sasha Grey, with long, fine dark hair, and oil-black eyes. Those eyes are world-weary like Scarlett Johansson's, […]
Happy Thanksgiving! Here is a Russian cartoon that was inexplicably dubbed with Sasha Grey's moans. And here is a horrified child watching it. Welcome to Russia! Please enjoy your stay. Read more...
Mya's "Ghetto Superstar" gets a revamp by a production ensemble including Goshfather (Victor Tapia and Jeremy Berger) and Sasha Grey. Together the 3 producers have injected the ubiquitous rap anthem with a dose of deep vibes that make us wish it was 1998 again.
When Sasha Grey goes for something, girl goes hard. And no, that's not just, like, some less-than-sly reference to her time in the adult film industry; it's a toast to this woman's commitment to whatever art project she decides to take...Show More Summary
Chivalry is dead. It was killed three iOS updates ago. Machinima's "Creepy Text Theater" might be doing the world a very important service. With live reenactments of perved out sexts, we get to see what our digital sex pleas sound like...Show More Summary
First, Sasha Grey walked away from pornography, and now she's doing the same with the abusive ex-boyfriend she claims lured her into porn in the first place -- he's been ordered to stay away from her... or go to jail.TMZ broke the story...…
Elijah Wood and Sasha Grey explore the murky stuff of Internet leaks and male entitlement in a thriller from the Timecrimes director. Spanish filmmaker Nacho Vigalondo picked a hell of a subject for his first English-language film. After...Show More Summary


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A new NIH grant, worth $425,000, will fund biomechanics research with a large potential impact on those who use prostheses to get around. This grant is the first since a record-setting $10.1 million award last year.
Beginning the Fall 2016 semester, UNO will offer a Bachelors of Science in Education with an Early Childhood Inclusive focus - bringing together faculty expertise from the Teacher Education Department and Special Education and Communication Disorders Department.
Martha Bruckner, B.S. '71 and M.S. '74, was Named the 2015-16 superintendent of the year by the School Administrators of Iowa organization. Courtney Matulka, B.S. '08 and M.S. '10, has been named Nebraska's 2015-16 Milken Educator.
Located in the School of HPER, Dr. Dustin Slivka is simulating extreme weather conditions, developing muscular research at the cellular level.
As the only degree of its kind in Nebraska and one of less than five in the entire country, UNO's new Bachelor of Science in Biomechanics is a continuation of UNO's commitment to cutting-edge research.
Jack McKay, Ed.D., former Professor Emeritus in the Department of Educational Leadership has been awarded for dedicating his career to public education advocacy.
Amelia Squires, STEM Outreach Coordinator, spent a week at NASA's Johnson Space Center at the LiftOff Summer Institute. Now she's back & ready to share her new expertise after learning about aerospace from NASA engineers and astronauts.
Play is a key element for early childhood development. Watch how early childhood graduate students helped design the PLAY exhibit at the Kaneko.
Secret Kindness Agents spread good will through small acts of generosity in metro area
Livewell Nebraska: UNO faculty give science cafe talk on transgender basics
WOWT - UNO Summer Program Exposes Young Women to STEM Fields
Omaha.com - Kaneko 'Play' Exhibit Collaboration with Early Childhood Program
Good Morning America: School of HPER Research Uncovers Why Grunting on the Tennis Court Actually Helps
Live with Kelly: School of HPER Research Touts Benefits of Grunting in Tennis Match
BRB's Dr. Mukherjee Demonstrates COBRE Grant Research with KETV's Alex Hoffman
$10.1 Million Research Grant a Major Stride for UNO As It Vies With the 'Big Boys'
All-year UNO Program for Student Teachers Stresses Field Experience
"For a beginning teacher, navigating the world of a new school environment can be difficult. The experience brings up a myriad of question and concerns-from how to inspire students to adapting to unique student needs. UNO's College of Education's partnership with the Metropolitan Omaha Educational Consortium serves to address these issues for new educators so they can find success and confidence."


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Connecting decision makers to a dynamic network of information, people and ideas, Bloomberg quickly and accurately delivers business and financial information, news and insight around the world.
+1 212 318 2000
Europe, Middle East, & Africa
+44 20 7330 7500
Asia Pacific
+65 6212 1000
Anybody who was still wondering if Facebook had noticed the rapid rise of Twitter need wonder no more. Today, Facebook announced it's buying FriendFeed, the news- and information-sharing service founded…
With what looks to be a fair amount of fanfare, a company virtually unknown in the U.S. is aiming to disrupt the fast-growing social networking business. Tonight, Rio de Janeiro-based…
Like plenty of digerati, apparently, I've discovered FriendFeed, a sort of social media- and feed-sharing aggregation service where I can "follow" a bunch of people's doings, whether they post stuff…
BusinessWeek writers Peter Burrows, Cliff Edwards, Olga Kharif, Aaron Ricadela, Douglas MacMillan, and Spencer Ante dig behind the headlines to analyze what's really happening throughout the world of technology. One of the first mainstream media tech blogs, Tech Beat covers everything from tech bellwethers like Apple, Google, and Intel and emerging new leaders such as Facebook to new technologies, trends, and controversies.


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Sundays at 6:00pm
620 West Kivett Street
Asheboro, NC
The first Vespers Mission of the North American Lutheran Church was Sunday, September 1, 2013. Thanks to all who came out in support.
Services the first year were held weekly at 6:00 PM in Greensboro's, NC. Due to renovations of that facility, we had to move elsewhere. We are now meeting at the Ryman's home (address above) for a lovely Vespers service. Nevertheless, we are looking for a new space for the mission in Alamance county.
Our worship follows the Service of Evening Prayer (Vespers) in the Lutheran Book of Worship. The vision of the Vespers Mission is twofold: to shine the light of Jesus Christ in the darkness and to form new mission congregations of the North American Lutheran Church.
Please join us some Sunday evening.


text:
Benefits of Registration
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Category: Windows 8 Sports Applications
Windows 8 Sports – ESPN Cricinfo0
Description The ESPN Cricinfo Windows 8 app provides comprehensive coverage of cricket from around the world from espncricinfo.com. With live ball-by-ball scoring, ...READ MORE +
Windows 8 Sports – FootballNews0
Description Follow the latest news from the NFL. Select your favorite teams and get the latest player news to keep up with your fantasy football news. Features Latest News in ...READ MORE +
Window 8 Sports – CS.Golf0
Description CS.Golf is complete offline database of golf courses in Czech republic. Each course shows its contact info, web link and basic course parameters. App is ad-free and ...READ MORE +
Windows 8 Sports – Live Tile Sport0
Description Get live news from your chosen sport in your Windows 8 UI! Features Multiple Sports Categories with associated Live Tiles Choice of Live tile Layout and Content ...READ MORE +
Windows 8 Sports – Sports1
Description The Sports app, powered by Bing, makes it easy for you to keep up with all the sports and teams you care about. Designed for Windows, the Sports app puts control at ...READ MORE +
Windows 8 Sports – FC Barcelona0
Description Have your team always with you ! FC Barcelona app provide you full list of Barcelona players , with full details. You can also share info about it ! Features Get ...READ MORE +
Windows 8 Sports – RacingNews0
Description Keep up with all of the latest racing news. You can choose from Nascar, Formula One, Indy, WRC, MotoGP, Le Mans, and GT Racing. Features Latest News in Nascar, ...READ MORE +
Windows 8 Sports – Major League Soccer0
Description The official Major League Soccer Windows 8 app brings the game to you. Follow the entire 2012 season from anywhere at anytime! Features Read news stories from ...READ MORE +
Windows 8 Sports – Gol Caracol0
Description Golcaracol.com es el portal de fútbol con todas las noticias, videos y goles del campeonato colombiano y los torneos y copas internacionales. Link to: Gol ...READ MORE +
Windows 8 Sports – Liga Postobón0
Description Reciba las mejores noticias del Fútbol Profesional Colombiano Features Últimas Noticias de la Liga Postobón Link to: Liga Postobón Cost: Free Category: ...READ MORE +


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The Brew Lounge
Telling the stories behind the passionate pursuit of great beer since 2005.
Wednesday, September 19, 2007
Getting Started in Homebrewing - The Process in Review
Click here for an index of Getting Started in Homebrewing
Here's a quick rundown of what I went through for my first homebrewing experience. A quick link to an index is at the top and bottom of this post. And, one last posting on the topic will be coming tomorrow, focused on 'lessons learned'...just in time for me to get started on my next batch! Bring 1.5 gallons to a boil - 20 minutes Boil, then reserve and allow to cool to room temperature; covered - 20 minutes Bring 3.5 gallons to a boil - 45 minutes Sanitize equipment with bleach - 30 minutes Kill flame, Add extract, Stir, Return to heat Bring back to rolling boil Add bittering hops Stir occasionally Add aroma hops - last 5 minutes Continue cooking over heat - 5 minutes Turn off heat Chill the wort with a wort chiller - 15 minutes Take hydrometer reading Pour wort into plastic fermenter Seal fermenter; add airlock Place primary fermenter in area where temperature is between 60F-75F Leave in plastic fermenter - 1 week Sanitize equipment Rack to secondary fermenter/glass carboy; add airlock Cover with blanket or paper bag Leave in area between 60F-75F - 2 weeks Sanitize equipment Move beer from secondary to bottling bucket (with spigot on bottom) Stir in priming sugar solution Bottle & Cap Store in cool, dark place for 1 week Taste one (for most styles, leave the sediment behind in bottle) Store at room or slightly cooler temperature for at least a couple more weeks Taste another one Optimal drinking for many styles may come as much as a month or two after bottling
Click here for an index of Getting Started in Homebrewing
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CHAUVET® DJ encourages customers to make safety a priority by utilizing the right clamps and cables for their lighting applications. Made of extruded aluminum, the CLP-06 wraps completely around truss for added security and stability.
• Wraps completely around truss for added security and stability
• Threaded Bolt: M12
• Load capacity: 220 lb (100 kg)
• Fits: 2 inch (50 mm) truss
• Weight: 1.1 lb (0.5 kg)
• Dimensions: 6.5 x 3.8 x 1.3 in (165 x 97 x 33 mm)
Specifications subject to change without notice.
Continental US
Worldwide Distributors
Online Retailers
SUNRISE, Fla. – Beginning DJs and party hosts who want to add some visual pop to their events with a colorful ...


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Forks as Place Card Holders
November 21, 2008
Apartment Therapy has a neat post about using fork tines as place card holders. Simple, classy, and keeps the table from looking cluttered. Regina writes:
With the fork tine idea, cards are placed as if you pranced around the table effortlessly tucking each card into place with a skip in your step and a laugh in your heart. I guess what I'm trying to say is the fork idea is not trying too hard, but it does the job with spare elegance.
Grooms: Carve a Thanksgiving Turkey Like a MAN
November 21, 2008
It's easy to fall into the trap of thinking that wedding planning and cooking and all these good things are only for the ladies, but nothing could be further from the truth. Professional kitchens have historically been the domain of manly men, and even today the majority of chefs- those people fussing over wedding menus and appetizer trays and plate garnishes- are guys.
So where to begin, my dear grooms? It's easy to let your eyes glaze over when hearing talk of napkin colors and matchbook engraving and floral foam, but there's a place for you in this mayhem too. A wedding reception is just a big party, and the core elements of any party are the music, the drinks, and the FOOD. Plus, choosing a menu and a cake usually involves tastings, where the venue or caterer woos you with their tasty skills. What's not to like?
And now holiday season is almost upon us, which is the perfect time to get some practice with the party planning scene. This is also your chance to impress the family, and maybe even the future in-laws, with some ninja turkey -carving skills. The Art of Manliness has a terrific post on cooking and carving a turkey, which walks you through the whole process from picking a turkey to packing up leftovers. Go take a look, print yourself a copy, and join the legions of men who confidently brave the heat in the kitchen.
Make It Ahead: For the Brave (and Slightly Crazy)
November 20, 2008
I bought a copy of this book last weekend, and I am unreasonably excited about it. Now, conventional wisdom says that a bride would need to be certifiably insane to even consider doing much wedding food on her own. It's a project not to be taken lightly, of course, but with the right amount of planning, preparation, and delegation (an essential part!) it is entirely possible to successfully cater your own wedding.
Over the next few months I'm looking forward to testing and writing about some of the most relevant recipes in the book, as well as a few make-ahead recipes of my own. Planning ahead is key to pulling off your own catering, and a menu of items that can be partially or fully prepared ahead of time is one of the best tools you have.
S'mores, Y'all!
November 19, 2008
There's a post over on Once Wed today about a bride who is clearly a real food lover. All the homemade details for the barbecue reception are just great, but she really won me over with the… wait for it… s'mores kits! Wow. The cupcake flags are great too, as well as her description of the reception decor. Go over there right now for more great photos of this lovely feast!
Cupcake Trees
November 18, 2008
Cupcakes are a great budget-saver as a wedding cake, easy to customize without going broke, and are a hit with guests. And, well, nothing says fun party like a giant cupcake tree! Here are some ideas to get your creative wheels turning. (photo via ModernJune) Read the rest of this entry »
A Sea-Glass Palette
November 17, 2008
I saw this great photo in the T-Cozy archives: a collection of sea glass that the author had found with her daughter over the years. What great colors! I think you could pull together a really relaxed, but classic look with this color range.
And So We Begin…
November 14, 2008
Welcome to A Chef's Fête!
What's all this about?
If you're planning a wedding or hosting a party, and you love to eat, this place is for you. A wedding is the perfect chance for many couples to showcase their special style and personalities; if one or both are food lovers, party planning can take on a whole different level of excitement. I look forward to sharing menus, recipes, tricks of the trade, and inspiration to help you make your celebration the very best it can be.
Who the heck are you?
I'm a baker by trade, with a hotel and catering background. I'm nearing the end of the Le Cordon Bleu culinary arts program; when I finish I aim to take a position as a pastry chef. There are few things in life better than a well-planned, well-executed party, and I'm excited to share my knowledge and experiences (and mistakes!) to help you create the event of your dreams.
If you see something and you want more, ask! If you think I can improve, say so. This is for you.


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Here' s an attempt to start a sensible discussion about the certain racial issues pertaining to RE5
I'm not looking to start a flame war, just want to hear intelligent views on what seems to have been a sensitive issue in the development of RE5
We have seen responses by some journalists and gamers about the use of Africa as a setting. Some have expressed some discomfort about the subject.
I think N'gai Croal of Newsweek has made some interesting observations and comments and I suggest people go Google and read it.
I have two questions to raise...
1) Do you think that people were over-reacting? With RE4 there was no big issue about the virtual slaughter of Spanish Villagers so why so touchy here?
2) Do you think that the developers had to reign in their original vision of the game/story to accomodate public opinion? Do you think that this is fair? How does this affect
the development of the medium as a mature (dare I say) artform?
Looking forward to some great responses.


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Husky Cousins by NightNikeWatch
©2011-2016 NightNike
Joker on the left and Odin on the right. It's hard to say from the first sight, but they're actually cousins. Though their different masks and everything else I found that they have simular body built instantly. It's just that Joker goes after his father, while Odin is a copy of his granny (exept for color). Despite all that they're going two completely different ways. As I already mentioned on the other photo, Joker is the Speed and Odin is the Brain of our team.
Photo by Efimenko Svetlana
Photo by Efimenko Svetlana


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Dango Spam by AmberStoneArtWatch
©2009-2016 AmberStoneArt
I wrote a blog-post thing today and it was usurped by the current comic making it appear twice in a row. So, I decided to upload a drawing to go with the post... which didn't work, either. It replaced the other one. Don't upgrade to the new webcomic. It's a pain in the ass. I am not enjoying it. Anyway, I took it down then reposted it with tomorrow's date, so this'll appear on the site in about an hour.
You should put up links to your website with every Dango post.
lol X3
What do I not upgrade to, again? I want to stay on top of the game... I think.
The new version of webcomic on wordpress.
great expression!
awww...dango got specs!!!! Super cuteee!!!


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Dedicated Volunteers work four hours a week for a six-month period within one department. This month's Volunteer Profile focuses on Kristen Friend and Caroline Brown Dedicated Volunteers for the Communications Department, who help design, create and distribute flyers, event notices, calendars and other communications materials for our sangha.
Kristen's StoryI learned of Spirit Rock almost simultaneously from an old friend in Florida and new friends in California. Shortly after I moved to San Rafael from Tampa, a group of women in a book club I had joined asked if I was interested in coming to a class at Spirit Rock with them. The same week, a friend from Tampa mentioned Spirit Rock—she had known of it before I moved and was encouraging me to go since I was so close. She was familiar with several of the teachers and recommended I take advantage of the offerings. I could not ignore such a coincidence, so I came with the women to a weekend class and was instantly drawn in by the sense of warmth and community that Spirit Rock offers.
I decided to volunteer because I felt there was a lack of balance in my life between the time I spent focused on work for my own gain and the time I spent helping to support others. I began volunteering about a year after I moved to California, at a time when I was becoming increasingly interested in deepening my ties to my new place. I had spent some time at Spirit Rock and was thrilled to find that they had volunteer spots available in which I could use my training as a designer. Finding such a fit in a volunteer opportunity is rare, and I am thankful for it.
Volunteering with the Communications Department in particular exposes me to the incredible variety of programs Spirit Rock offers to the community. I have been able to explore teachings that have added to my own practice, and I have been able to help bring others who are interested in these offerings to Spirit Rock as well. Volunteering has actually helped deepen some of my relationships with friends who I would not otherwise have known shared my desire to be a part of the Spirit Rock community. I have also met wonderfully talented people who continue to give me ideas and inspiration that I can use in my daily life as a graphic designer. I am given the chance to work on projects that cause me to shift my thinking away from my usual patterns and help reboot my creativity.Volunteering has added a gentle sense of calm to my life; it helps chip away at the daily stresses that build up every week. I know that for at least a day every week, I am tuned out of my routine and focused on working for the sake of the work itself—for the value it brings to others. Being able to help out in any way—even the little things—is rewarding. I always leave Spirit Rock much more centered than I when I arrive and with a better perspective on the week to come.
Caroline's StoryWhen I still lived on the East Coast, I learned about Spirit Rock from a friend who had been on retreat with Jack. This led me to read a lot of teachings from Spirit Rock teachers and listen to many Spirit Rock dharma recordings. When I moved to the East Bay in 2012 I was excited to attend some daylongs. These positive experiences made me want to be more involved. I'm grateful that I get to help Spirit Rock spread the Dharma.
Volunteering at Spirit Rock has helped me inch out of my comfort zone. I'm a writer, so I usually work on large research and writing projects that take several weeks or months to finish. That's very different from my work in the Communications Department, where I have a variety of tasks that require me to pay attention to detail and work quickly at the same time—something that I don't think I'm very good at.
My inner critic is out in force when I volunteer, urging me to work faster and scolding me for making mistakes. So by experiencing new ways of working and trying new tasks, I'm learning a lot about my inner critic and myself. In this way, volunteering at Spirit Rock has actually become a part of my practice and is helping me be more mindful, aware, accepting and forgiving.
I've been self-employed for the last 12 years, working by myself from my home office and communicating with others mostly via email. I really appreciate the opportunity to work and interact with "real" people instead of electronic ones.
Spirit Rock relies on the generosity of our many volunteers. We offer a range of volunteer opportunities from one time projects to ongoing service. Check our website to find out more about our volunteer program or contact our Volunteer & Community Coordinator, Marya Mayer, firstname.lastname@example.com.


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Regional Outlooks
Developing economies are facing two key transitions, according to the June 2015 issue of Global Economic Prospects. First, with an imminent rise likely in U.S. interest rates, borrowing will become more expensive for emerging and developing economies over the coming months. This process is expected to unfold smoothly since the US economic recovery is continuing and interest rates remain low in other major global economies. Second, lower oil prices are having an increasingly pronounced impact. In oil-importing countries, the benefits to activity have so far been limited, although they are helping to reduce vulnerabilities. In oil-exporting countries, lower prices are sharply reducing activity and increasing fiscal, exchange rate, or inflationary pressures.
The links below provide access to six detailed regional reports and to extensive economic data, including forecasts through 2017.


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Red Lion's Graphite® advanced operator panels are the industry's first HMI touchscreens to combine a rugged yet aesthetically-pleasing all-aluminum construction with a modular I/O architecture. All of the Graphite models offer drag-and-drop protocol conversion, data logging and web-based monitoring and control. With UL Class 1, Division 2, ABS, ATEX and IECEx approvals, Graphite enables customers to connect, monitor and control processes in harsh environments.
Available in 8 different models | Remote monitoring and control | Converts over 300 protocols
Sleek. Rugged. Flexible.
No matter what you need your HMI to connect, monitor and control, we've got you covered with the new Graphite series. It's one of the first HMIs that sleek, flexible and built for extreme conditions. Developed from our customers' feedback, Red Lion has taken HMIs to the next level. Graphite features include:
Attractive, Sleek & Easy to Use – Ideal for indoor and harsh outdoor environments, Graphite is available in 7 inch, 9 inch, 10 inch, 12 inch and 15 inch displays, with a relatively large screen that's easy to view even in direct sunlight. Its small footprint saves space and money.
Rugged Case for Extreme Conditions – Cast-aluminum housing means you can take Graphite into oil fields, wastewater plants or other extreme conditions without a worry. Built to operate in temperatures between -20 to 60 degrees Celsius, it's ideal for tough environments.
Flexible Modules Expand with Your Business – Graphite's plug-in modules minimize development and commissioning times over traditional systems that use an HMI paired with separate I/O, PLCs and other controllers. Create a solution today that easily expands to satisfy your future business requirements.
Built-in Protocol Conversion – With a few clicks of the mouse, Graphite can be quickly setup to exchange data between all your connected devices. Select over 13 simultaneous protocols from a list of over 300 to integrate disparate devices such as PLCs, drives, barcode readers and panel meters.
Real-Time Data Logging – By logging real-time performance data, including productivity and output comparisons, you can implement process improvements or quickly pinpoint bottlenecks or chokepoints.
Remote Monitoring & Control – With Graphite's built-in web server, remotely monitor and control your application via PCs, tablets or smartphones. When problems occur, automatic SMS text-messaging and email alerts are sent to your maintenance team.


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Find more
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Help more babies in Alabama start life healthy and strong.
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The March of Dimes Alabama Chapter funds programs that help moms have full-term pregnancies and healthy babies. This includes providing financial support to research and education that will help moms before and during their pregnancies. It also includes working with local medical groups and organizations to improve prenatal care and newborn screening.
Grants and awards are given to projects that address the urgent needs of moms and babies. Grants are generally
awarded for one to three years and range from $10,000 to $25,000.
The Alabama Chapter uses gifts wisely. The chapter community grants program is designed to invest in priority
projects that further the March of Dimes mission, support national and state objectives, and further our strategic
goal of reducing disparities in birth outcomes. We award grants based on a number of criteria, including the group
or organization's ability to accomplish its goals, as well as the potential impact a project will have in helping
us prevent premature births, birth defects and infant mortality. Proposals will be accepted from organizations
focusing on one of the following priorities:
- Providing or enhancing premature birth risk reduction education and/or services. Risk reduction projects are limited to:
*Providing smoking cessation education and/or services to pregnant women. Preference should be given to prenatal health education and information/referral services that utilize evidence-based counseling approaches.
Increasing health education and information/referral services available to pregnant women who use alcohol or other drugs.
*Implementing home visiting programs (i.e. Early Head Start-Home Visiting, Early Intervention Program for Adolescent Mothers, Healthy Families America (HFA), Nurse Family Partnership®).
- Providing or enhancing education and/or services for populations at greatest risk for preterm birth and infant mortality.
*Enhancing health education and information/referral services that aim to reduce racial/ethnic disparities in preterm birth.
*Implementing community programs that aim to promote equity in birth outcomes. This may include March of Dimes programs like Stork's Nest®1, Project Alpha, Becoming a Mom/Comenzando bien®, and The Coming of the Blessing®.
- Supporting a quality improvement program related to premature birth prevention with the goal of catalyzing systems change.
- Providing or enhancing preconception health education and/or services. For more information, see the Centers for Disease Control and Prevention Preconception Health and Health Care resources for health professionals at: www.cdc.gov/preconception.
In order to be eligible to receive a March of Dimes chapter grant, an organization must be an incorporated not-for-profit 501(c)(3) or for profit organization or government agency. The March of Dimes does not award grants to individuals. Applicants must disclose any conflict of interest due to representation by their organization on the chapter's Program Services Committee or the Chapter or Division Board of Directors.
2015-2016 Community Grant Application
Submission Requirements:
To apply, applicants should first review the full application, guidelines and required forms. Proposals must address at least one of the funding priorities mentioned. Please be advised that proposals are non-binding. Electronic submission responses need to be received no later than 4:00PM CST, August 3, 2015. Submissions must be in Word (.doc) or PDF (.pdf) format.
Hardcopy submissions must be received by August 3, 2015 and should be sent to:
Kimberly Seals
March of Dimes
450 Century Park South, Suite 200-B
Birmingham, AL 35226
Proposals will be reviewed by a multi-disciplinary Program Services Committee. 2015 applicants will be notified of their proposal's status in September 2015. 2016 applicants will be notified of their proposal status in January 2016. The grant period is from February 1, 2016 – January 31, 2017.
Help more babies in Alabama start life healthy and strong.
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August 13- November 12, 2015
Experience the challenges of the next generation of space exploration.
August 13 - November 12, 2015
Zip through other-worldly wormholes, experience the creation of the Milky Way, and witness the violent death of a star and subsequent birth of a black hole.
Starting from the outermost reaches of the solar system, take a cosmic journey from Pluto to Earth. Zoom past planets revolving above you.
A brilliant spectacle of light and color follows Sesame Street's Big Bird and Elmo as they explore the night sky with Hu Hu Zhu, a new friend from China.
Imagine the ultimate space vacation! Discover our solar system through a new set of eyes—a family from another star system seeking the perfect vacation spot.
Earth. It's now a small world. The human race is connected better and faster than ever before but what about elsewhere?
November 13, 2015- June 2, 2016
Explore space like never before in the live show Destination Solar System!


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Blue sakura dragon - design by AlviaAlcedoWatch
©2013-2016 AlviaAlcedo
So are you saying WE can use it? If so you're super awesome!
Цвет такой плавный получается о-о будто и не карандаши вовсе. хочу такие х)
wow very beautiful!
Absolutely Breathtaking!
Beautiful dragon!
Aww so pretty!
whoa awesome!!!
Amazing design!!
very well done! the movement is awesome as well!
Love this design, it showers peace over my emotions just looking at it
It's a beauty..<3
Love, love, love!!
beauty and amazing skills you have even an creative mind you have here great job keep it up dude
wow it is so pretty
I love it really beautiful
*O* So perfect! Thank you sooooooo much^^
I will have the greatest tatto in the world thanks to you
I will have the greatest tatto in the world thanks to you
I um... love this.
simply beautiful
Lovely; I love dragons with long body like this!
Now this would make an awesome tat !
amazingly beautiful, yet again
sooooo cute!
hmmmm ? looks like something I knwo wonderfull
Oh gosh this is lovely!
I love it!
I love it! If I was a tatoo kind of person ( I'm not a big fan of needles) I would totaly get this as a tatoo. I've probably said this before, but I love how you make it look like it was painted or printed, rather than colored in. Your art is always beautiful!
aw so pretty ♥
I build $82h whereas i am traveling the planet. Last week I worked by my laptop computer in Rome, Monti carlo and at last Parisâ¦This week i am back within the USA. All I do square measure simple tasks from this one cool web site. check it out,,,,.. www.Jobs81.ℂom
absolutely awesome
nice and cute
incredible control of media...
This is absolutely beautiful.
How exactly do you do the eyes with such small tools?
I love eastern dragons, and in your style, I love them even more. Beautiful!
oh wow! i would totally stretch this out a bit for a long sidepiece! LOVE IT!!


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Content related to 'TFM-June-2012'
June 2012 Issue (Volume 25, Number 6)06 . 18 . 12
Find out how technology can assist project management and building automation in this issue.
Services & Maintenance: The Right Fit06 . 13 . 12
When seeking pre-owned furniture, a little research can go a long way toward finding a suitable dealer.
The HVAC Factor: How Does That Sound?06 . 13 . 12
In education facilities, acoustical considerations can impact learning.
Professional Development: Lightning Safety Tips06 . 13 . 12
On average, lightning kills more people than hurricanes and tornadoes combined every year.
FM Frequency: Machines Don't Clean Buildings…People Do: Part 206 . 12 . 12
In the second part of this examination, Carpenter breaks down the realities of finding the right player for the cleaning game in your facility.
FM Issue: Say What You Mean!06 . 12 . 12
A facility management strategy that aligns with the broader organization vision is increasingly important. It is possible to develop and articulate a workplace approach that is aligned with technology.
Building Automation Trends: Beyond The Building06 . 12 . 12
There are many ways managers can facilitate a smarter physical infrastructure. By collecting and analyzing data, managers can discover opportunities for efficiency within and around their facilities.
Corporate Headquarters Case Study: Across The Board06 . 12 . 12
A global headquarters campus in Glendale, WI undergoes a major overhaul including an expansion that employed technology and sustainability to move operations to the next level.


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3 days past its "sell by" date or "use by" date? Regardless, since it's smoked and it's cheese, it's probably fine. I'd use it. Just check it carefully for any signs of mold or decay--strange coloring or strange odors.
pierino is a trusted source on General Cooking and Tough Love.
Should be no problem. The smoking process is intended to make it taste interesting but also hold longer. In Italy an equivalent cheese would be scamorza. It's a low moisture cheese so it doesn't have to be consumed immediately.
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The School of Nursing originated as a diploma program at Our Lady of the Lake Hospital in 1923. In 1990, Our Lady of the Lake College was established based on the recommendation of the nursing faculty. The diploma program was transitioned to an Associate of Science in Nursing program. The first class was admitted in 1990. As a result of changes in health care, the nursing faculty proposed transitioning the associate degree program into a Bachelor of Science in Nursing program. The College Board of Trustees approved this transition. The BSN program admitted its first class fall 2012.
The purpose of the Our Lady of the Lake College BSN Program is to provide students with a strong educational basis by building on a liberal education in the arts and sciences. The program prepares competent, self-directed generalists to assume leadership roles in the delivery of evidenced-based nursing care. The baccalaureate program establishes a solid foundation for graduate education, professional leadership roles, and career enhancement by providing the knowledge and skills essential to practice in a rapidly changing health care environment. The program graduate of this program receives a Bachelor of Science in Nursing degree and is eligible to write the National Council Licensure Examination for Registered Nurses (NCLEX-RN).
Applicants to the pre-licensure Bachelor of Science in Nursing program must complete an application specific to the BSN program. Applications are due on or before January 15 for the August class or July 15 for the January class.
Length of Program
The Bachelor of Science in Nursing program consists of 120 credit hours. Once accepted into the BSN program, students must complete the nursing courses within five years.
Application Procedures
Visit www.ololcollege.edu or contact the Office of Admissions at 225-768-1700.
See the Tuition & Fee Schedule
Financial Assistance
Our Lady of the Lake College has financial aid counselors available to assist students with the financial aid process. All students are encouraged to complete the Free Application for Federal Student Aid (FAFSA) form available at www.fafsa.ed.gov.
Refer to the current college catalog regarding transferability of arts and sciences courses taken at other regionally accredited colleges and universities. Further information regarding transfer of credit can be obtained at the Office of Admissions. Nursing students currently or previously enrolled in other nursing programs who desire admission by transfer of credit should consult the current college catalog for additional information.
Our Lady of the Lake College is accredited by the Southern Association of Colleges and Schools Commission on Colleges to award associate, baccalaureate, masters and doctorate degrees. Contact the Commission on Colleges at 1866 Southern Lane, Decatur, Georgia 30033-4097 or call 404-679-4500 for questions about the accreditation of Our Lady of the Lake College. All School of Nursing BSN programs are fully approved by the Louisiana State Board of Nursing (17373 Perkins Road, Baton Rouge, Louisiana 70810, (225) 755-7500, http://www.lsbn.state.la.us) and hold accreditation from the Accreditation Commission for Education in Nursing (3343 Peachtree Rd. NE, Suite 850, Atlanta, GA 30326, (404) 975-5000, http://www.acenursing.org).


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You are a fan of suffciency tragger ? Come to discover the best forums suffciency tragger on the internet and share your experience with a community fan of suffciency tragger . You can also build a forum suffciency tragger and create your online discussion.
A forum for those seeking a simpler and more sustainable way of life.
green, forum, homemade, life, smallholding, voluntary, simplicity, self, #suffciency, folk, downshift, downsize, reliance, living, crafting, heritage, crafts, bodger


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Talk:Sinusoid (blood vessel)
|WikiProject Anatomy
|(Rated Stub-class, Mid-importance)
Partly Taken From Dr. Moore's Handout Ross University School of Medicine Sept. 2005. (Comment moved from article by Andreas (T) 16:01, 22 May 2006 (UTC))
But sinusoids themselves aren't drawn in the image from Gray's anatomy?[edit]
It seems to me they aren't drawn in the image.
"Sinusoid" caption in this picture should have a meaning close to "sinusoid space", if I'm not mistaken. It was rather hard to understand the structure of the lobule and the sinusoids' role in it from the Gray's image. This page has great images taken at different magnification. It'd be great to have several images with different magnifications in the WikiCommons, to present them one by one to the reader so he can get an idea of a sinusoid vessel. --CopperKettle 08:14, 27 August 2006 (UTC)
Can someone who knows what they're doing possibly fix up the last few sentences? They're more than a little off tone for Wikipedia, and I'm not 100% clear what they're trying to say (hence not doing it myself). 188.8.131.52 (talk) 16:25, 2 July 2011 (UTC)