FEM modeling of structure and properties of diamond-SiC-(Al) composites developed for thermal management applications

Thermal management materials frequently have multi-phase composite character with complex architecture of the constituents. As a result, design rules are needed which can be used in selection of the phases and optimizing their volume fractions. The study shows that such are provided by finite element modeling of these composites. This is demonstrated for a diamond-SiC-Si-(Al) composites, which have been optimized in terms of the volume fraction of SiC, contact area between the components and presence of open porosity

Brazilian multicenter study on pegvisomant treatment in acromegaly

Objective Investigate the therapeutic response of acromegaly patients to pegvisomant (PEGV) in a real-life, Brazilian multicenter study. Subjects and methods Characteristics of acromegaly patients treated with PEGV were reviewed at diagnosis, just before and during treatment. All patients with at least two IGF-I measurements on PEGV were included. Efficacy was defined as any normal IGF-I measurement during treatment. Safety data were reviewed. Predictors of response were determined by comparing controlled versus uncontrolled patients. Results 109 patients [61 women; median age at diagnosis 34 years; 95.3% macroadenomas] from 10 Brazilian centers were studied. Previous treatment included surgery (89%), radiotherapy (34%), somatostatin receptor ligands (99%), and cabergoline (67%). Before PEGV, median levels of GH, IGF-I and IGF-I % of upper limit of normal were 4.3 µg/L, 613 ng/mL, and 209%, respectively. Pre-diabetes/diabetes was present in 48.6% and tumor remnant in 71% of patients. Initial dose was 10 mg/day in all except 4 cases, maximum dose was 30 mg/day, and median exposure time was 30.5 months. PEGV was used as monotherapy in 11% of cases. Normal IGF-I levels was obtained in 74.1% of patients. Glycemic control improved in 56.6% of patients with pre-diabetes/diabetes. Exposure time, pre-treatment GH and IGF-I levels were predictors of response. Tumor enlargement occurred in 6.5% and elevation of liver enzymes in 9.2%. PEGV was discontinued in 6 patients and 3 deaths unrelated to the drug were reported. Conclusions In a real-life scenario, PEGV is a highly effective and safe treatment for acromegaly patients not controlled with other therapies

Diagnosis, Genetics, and Therapy of Short Stature in Children: A Growth Hormone Research Society International Perspective

The Growth Hormone Research Society (GRS) convened a Workshop in March 2019 to evaluate the diagnosis and therapy of short stature in children. Forty-six international experts participated at the invitation of GRS including clinicians, basic scientists, and representatives from regulatory agencies and the pharmaceutical industry. Following plenary presentations addressing the current diagnosis and therapy of short stature in children, breakout groups discussed questions produced in advance by the planning committee and reconvened to share the group reports. A writing team assembled one document that was subsequently discussed and revised by participants. Participants from regulatory agencies and pharmaceutical companies were not part of the writing process. Short stature is the most common reason for referral to the pediatric endocrinologist. History, physical examination, and auxology remain the most important methods for understanding the reasons for the short stature. While some long-standing topics of controversy continue to generate debate, including in whom, and how, to perform and interpret growth hormone stimulation tests, new research areas are changing the clinical landscape, such as the genetics of short stature, selection of patients for genetic testing, and interpretation of genetic tests in the clinical setting. What dose of growth hormone to start, how to adjust the dose, and how to identify and manage a suboptimal response are still topics to debate. Additional areas that are expected to transform the growth field include the development of long-acting growth hormone preparations and other new therapeutics and diagnostics that may increase adult height or aid in the diagnosis of growth hormone deficiency.info:eu-repo/semantics/publishedVersio

GH safety workshop position paper: A critical appraisal of recombinant human GH therapy in children and adults

Recombinant human GH (rhGH) has been in use for 30 years, and over that time its safety and efficacy in children and adults has been subject to considerable scrutiny. In 2001, a statement from the GH Research Society (GRS) concluded that 'for approved indications, GH is safe'; however, the statement highlighted a number of areas for on-going surveillance of long-Term safety, including cancer risk, impact on glucose homeostasis, and use of high dose pharmacological rhGH treatment. Over the intervening years, there have been a number of publications addressing the safety of rhGH with regard to mortality, cancer and cardiovascular risk, and the need for long-Term surveillance of the increasing number of adults who were treated with rhGH in childhood. Against this backdrop of interest in safety, the European Society of Paediatric Endocrinology (ESPE), the GRS, and the Pediatric Endocrine Society (PES) convened a meeting to reappraise the safety of rhGH. The ouput of the meeting is a concise position statement

Models predicting the growth response to growth hormone treatment in short children independent of GH status, birth size and gestational age

<p>Abstract</p> <p>Background</p> <p>Mathematical models can be used to predict individual growth responses to growth hormone (GH) therapy. The aim of this study was to construct and validate high-precision models to predict the growth response to GH treatment of short children, independent of their GH status, birth size and gestational age. As the GH doses are included, these models can be used to individualize treatment.</p> <p>Methods</p> <p>Growth data from 415 short prepubertal children were used to construct models for predicting the growth response during the first years of GH therapy. The performance of the models was validated with data from a separate cohort of 112 children using the same inclusion criteria.</p> <p>Results</p> <p>Using only auxological data, the model had a standard error of the residuals (SD_res), of 0.23 SDS. The model was improved when endocrine data (GH_maxprofile, IGF-I and leptin) collected before starting GH treatment were included. Inclusion of these data resulted in a decrease of the SD_resto 0.15 SDS (corresponding to 1.1 cm in a 3-year-old child and 1.6 cm in a 7-year old). Validation of these models with a separate cohort, showed similar SD_resfor both types of models. Preterm children were not included in the Model group, but predictions for this group were within the expected range.</p> <p>Conclusion</p> <p>These prediction models can with high accuracy be used to identify short children who will benefit from GH treatment. They are clinically useful as they are constructed using data from short children with a broad range of GH secretory status, birth size and gestational age.</p

Prediction models for short children born small for gestational age (SGA) covering the total growth phase. Analyses based on data from KIGS (Pfizer International Growth Database)

<p>Abstract</p> <p>Background</p> <p>Mathematical models can be developed to predict growth in short children treated with growth hormone (GH). These models can serve to optimize and individualize treatment in terms of height outcomes and costs. The aims of this study were to compile existing prediction models for short children born SGA (SGA), to develop new models and to validate the algorithms.</p> <p>Methods</p> <p>Existing models to predict height velocity (HV) for the first two and the fourth prepubertal years and during total pubertal growth (TPG) on GH were applied to SGA children from the KIGS (Pfizer International Growth Database) - 1^styear: N = 2340; 2^ndyear: N = 1358; 4^thyear: N = 182; TPG: N = 59. A new prediction model was developed for the 3^rdprepubertal year based upon 317 children by means of the all-possible regression approach, using Mallow's C(p) criterion.</p> <p>Results</p> <p>The comparison between the observed and predicted height velocity showed no significant difference when the existing prediction models were applied to new cohorts. A model for predicting HV during the 3^rdyear explained 33% of the variability with an error SD of 1.0 cm/year. The predictors were (in order of importance): HV previous year; chronological age; weight SDS; mid-parent height SDS and GH dose.</p> <p>Conclusions</p> <p>Models to predict growth to GH from prepubertal years to adult height are available for short children born SGA. The models utilize easily accessible predictors and are accurate. The overall explained variability in SGA is relatively low, due to the heterogeneity of the disorder. The models can be used to provide patients with a realistic expectation of treatment, and may help to identify compliance problems or other underlying causes of treatment failure.</p

Cutoff for body mass index in adolescents: comparison with national and international reference standards

OBJETIVO: elaborar uma tabela percentílica para o índice de massa corporal (IMC) para adolescentes na faixa etária de 10 a 14 anos da cidade de Curitiba, Paraná, e comparar os valores encontrados para o sobrepeso (percentil 85) e obesidade (percentil 95) com referências de IMC nacional, regional e internacional. MÉTODO: estudo longitudinal misto com 5231 avaliações, 2471 em meninos e 2760 em meninas, idades entre 10 e 14 anos. Esse número foi obtido a partir de avaliações semestrais realizadas entre os anos de 1998 a 2002, gerando 4321 observações (estudo longitudinal), mais a avaliação de 910 indivíduos no ano de 2006 (estudo transversal). O IMC foi calculado pela razão entre a massa corporal (Kg) dividida pela estatura (m) ao quadrado. Foram elaboradas tabelas de frequência baseadas na distribuição percentílica. Para identificar as diferenças nos pontos de corte para sobrepeso e obesidade com os estudos nacionais de Cintra e de Conde e Monteiro e com o estudo internacional de Cole foi utilizado teste binomial não paramétrico. RESULTADOS: comparando com as referências, os jovens de Curitiba seriam superestimados com sobrepeso se utilizadas a referência de Conde e a de Cole e subestimados na referência regional de Cintra. As mesmas tendências foram observadas com relação ao percentil 95 (obesidade), porém não para todas as faixas etárias. CONCLUSÃO: observamos diferenças nos valores de IMC sugeridos como pontos de corte para sobrepeso e obesidade em relação às referências nacionais e internacionais reforçando a necessidade de utilização de referências específicas para cada população.OBJECTIVE: to develop a scale percentile for body mass index (BMI) for adolescents aged 10 to 14 years from the city of Curitiba, Paraná, and compare the values found for overweight (85th percentile) and obesity (95th percentile) with references to national and international BMI. METHOD: mixed longitudinal study with 5231 evaluation, 2471 in boys and girls in 2760, aged 10 and 14 years. This number was obtained from semester evaluations conducted between the years 1998 to 2002, generating 4321 observations (longitudinal study), further evaluation of 910 individuals in 2006 (cross-sectional study). BMI was calculated as the ratio of body mass (kg) divided by height (m) squared. Frequency tables were prepared based on the percentile distribution. To identify differences in cut-off points for overweight and obesity with the national study of Cintra, and Conde and with the international study of Cole non-parametric binomial test was used. RESULTS: compared with the references, the young people of Curitiba were overestimated overweight if used for the reference of Conde and Cole and underestimated in the regional reference Cintra. The same trends were observed with respect to the 95th percentile (obesity), but not for all ages. CONCLUSION: we observed differences in the values of BMI suggested as cut-off points for overweight and obesity in relation to national and international references emphasizing the need to use specific references for each population

Age Affects the Expression of Maternal Care and Subsequent Behavioural Development of Offspring in a Precocial Bird

Variations of breeding success with age have been studied largely in iteroparous species and particularly in birds: survival of offspring increases with parental age until senescence. Nevertheless, these results are from observations of free-living individuals and therefore, it remains impossible to determine whether these variations result from parental investment or efficiency or both, and whether these variations occur during the prenatal or the postnatal stage or during both. Our study aimed first, to determine whether age had an impact on the expression of maternal breeding care by comparing inexperienced female birds of two different ages, and second, to define how these potential differences impact chicks’ growth and behavioural development. We made 22 2-month-old and 22 8-month-old female Japanese quail foster 1-day-old chicks. We observed their maternal behaviour until the chicks were 11 days old and then tested these chicks after separation from their mothers. Several behavioural tests estimated their fearfulness and their sociality. We observed first that a longer induction was required for young females to express maternal behaviour. Subsequently as many young females as elder females expressed maternal behaviour, but young females warmed chicks less, expressed less covering postures and rejected their chicks more. Chicks brooded by elder females presented higher growth rates and more fearfulness and sociality. Our results reveal that maternal investment increased with age independently of maternal experience, suggesting modification of hormone levels implied in maternal behaviour. Isolated effects of maternal experience should now be assessed in females of the same age. In addition, our results show, for first time in birds, that variations in maternal care directly induce important differences in the behavioural development of chicks. Finally, our results confirm that Japanese quail remains a great laboratory model of avian maternal behaviour and that the way we sample maternal behaviour is highly productive

Bariatric surgery for hypothalamic obesity in craniopharyngioma patients: a retrospective, matched case-control study

Context: Craniopharyngioma is a sellar tumor associated with high rates of pituitary deficiencies (similar to 98%) and hypothalamic obesity (similar to 50%).Objective: This work aims to determine the efficacy regarding long-term weight loss after bariatric surgery in obese craniopharyngioma patients with hypothalamic dysfunction.Methods: This retrospective, case-control, multicenter, international study included obese craniopharyngioma patients (N=16; of whom 12 are women) with a history of bariatric surgery (12 Roux-en-Y gastric bypass, 4 sleeve gastrectomy; median age 21 years [range, 15-52 years], median follow-up 5.2 years [range, 2.0-11.3 years]) and age/sex/surgery/body mass index-matched obese controls (N=155). Weight loss and obesity-related comorbidities up to 5 years after bariatric surgery were compared and changes in hormonal replacement therapy evaluated.Results: Mean weight loss at 5-year follow-up was 22.0% (95% CI, 16.1%-27.8%) in patients vs 29.5% (95% CI, 28.0%-30.9%) in controls (P=.02), which was less after Roux-en-Y gastric bypass (22.7% [16.9%-28.5%] vs 32.0% [30.4%-33.6%]; P=.003) but at a similar level after sleeve gastrectomy (21.7% [-1.8% to 45.2%] vs 21.8% [18.2%-25.5%]; P=.96). No major changes in endocrine replacement therapy were observed after surgery. One patient died (unknown cause). One patient had long-term absorptive problems.Conclusion: Obese patients with craniopharyngioma had a substantial mean weight loss of 22% at 5-year follow-up after bariatric surgery, independent of type of bariatric surgery procedure. Weight loss was lower than in obese controls after Roux-en-Y gastric bypass. Bariatric surgery appears to be effective and relatively safe in the treatment of obese craniopharyngioma patients.Development and application of statistical models for medical scientific researc

Growth Hormone Research Society perspective on the development of long-acting growth hormone preparations

Objective The Growth Hormone (GH) Research Society (GRS) convened a workshop to address important issues regarding trial design, efficacy, and safety of long-acting growth hormone preparations (LAGH). Participants A closed meeting of 55 international scientists with expertise in GH, including pediatric and adult endocrinologists, basic scientists, regulatory scientists, and participants from the pharmaceutical industry. Evidence Current literature was reviewed for gaps in knowledge. Expert opinion was used to suggest studies required to address potential safety and efficacy issues. Consensus process Following plenary presentations summarizing the literature, breakout groups discussed questions framed by the planning committee. Attendees reconvened after each breakout session to share group reports. A writing team compiled the breakout session reports into a draft document that was discussed and revised in an open forum on the concluding day. This was edited further and then circulated to attendees from academic institutions for review after the meeting. Participants from pharmaceutical companies did not participate in the planning, writing, or in the discussions and text revision on the final day of the workshop. Scientists from industry and regulatory agencies reviewed the manuscript to identify any factual errors. Conclusions LAGH compounds may represent an advance over daily GH injections because of increased convenience and differing phamacodynamic properties, providing the potential for improved adherence and outcomes. Better methods to assess adherence must be developed and validated. Long-term surveillance registries that include assessment of efficacy, cost-benefit, disease burden, quality of life, and safety are essential for understanding the impact of sustained exposure to LAGH preparations