El método de Nelder-Mead para minimización irrestricta sin derivadas

En este trabajo presentamos el método de Nelder-Mead, junto a algunos resultadm· teóricos recientes y ejemplos numéricos

Estudio numérico de algoritmos determinísticos para problemas de optimización sin derivadas

En este trabajo se presenta un estudio numérico de algoritmos para resolver problemas de optimización sin derivadas basados en los dos principales enfoques determinísticos: métodos basados en búsqueda de patrones y métodos basados en interpolación polinomial junto con estrategias de región de confianza. Se analizan algunas de sus implementaciones m´as conocidas, incluyendo comparaciones usando un conjunto de problemas test.Sociedad Argentina de Informática e Investigación Operativ

El método de Newton y estrategias de globalización para la resolución numérica de ecuaciones no lineales

En este trabajo se considera el método de Newton para la resolución numérica de ecuaciones no lineales y se estudian algunas estrategias de globalización basadas en el método de Bisección

Estudio numérico de algoritmos determinísticos para problemas de optimización sin derivadas

En este trabajo se presenta un estudio numérico de algoritmos para resolver problemas de optimización sin derivadas basados en los dos principales enfoques determinísticos: métodos basados en búsqueda de patrones y métodos basados en interpolación polinomial junto con estrategias de región de confianza. Se analizan algunas de sus implementaciones m´as conocidas, incluyendo comparaciones usando un conjunto de problemas test.Sociedad Argentina de Informática e Investigación Operativ

Rango numérico de una matriz compleja

En este trabajo se estudia el concepto de rango numérico de una matriz compleja y se presenta un algoritmo para obtener una representación aproximada en el plano complejo del rango numérico de una matriz compleja. Se muestran algunos ejemplos numéricos y su representación gráfica

Estudio numérico de algoritmos determinísticos para problemas de optimización sin derivadas

En este trabajo se presenta un estudio numérico de algoritmos para resolver problemas de optimización sin derivadas basados en los dos principales enfoques determinísticos: métodos basados en búsqueda de patrones y métodos basados en interpolación polinomial junto con estrategias de región de confianza. Se analizan algunas de sus implementaciones m´as conocidas, incluyendo comparaciones usando un conjunto de problemas test.Sociedad Argentina de Informática e Investigación Operativ

Treatment of GH-deficient children with two different GH doses: effect on final height and cost-benefit implications

OBJECTIVE: Treatment of GH-deficient (GHD) children with higher doses of recombinant human GH (rhGH) than conventional ones has been reported to result in higher growth velocity and increased final height. These findings, however, were observed by comparing large but heterogeneous groups of children. We wanted to verify whether the same results could be obtained in two groups of appropriately well-matched children with isolated GHD treated with high vs conventional doses of rhGH. METHODS: Out of two cohorts of GHD children, cohort A (on a weekly rhGH dose of 0.3 mg/kg body weight) and cohort B (on a weekly rhGH dose of 0.15 mg/kg body weight), we selected two groups, each including 13 patients, who before treatment were matched for age, sex and height standard deviation score (SDS). They were followed up until final height. RESULTS: Final height SDS was significantly higher in group A (-0.45+/-0.36 (s.d.) vs -1.07+/-0.7; P=0.008), as well as height gain SDS (1.81+/-0.58 vs 1.23+/-0.62; P=0.002). The difference between final height SDS and target height SDS was positive only in group A and significantly higher in group A than in group B (0.33+/-0.51 vs -0.46+/-0.7; P=0.01). Glucose tolerance was always normal in the group treated with higher doses. CONCLUSION: The final height of children treated with higher doses of rhGH is increased, also in relation to their genetic target. The economical burden of this choice of treatment, however, has to be taken into account when evaluating the results

Growth hormone therapy and respiratory disorders: Long-term follow-up in PWS children

Context: Adenotonsillar tissue hypertrophy and obstructive sleep apnea have been reported during short-term GH treatment in children with Prader-Willi syndrome (PWS). Objective: We conducted an observational study to evaluate the effects of long-term GH therapy on sleep-disordered breathing and adenotonsillar hypertrophy in children with PWS. Design: This was a longitudinal observational study. PatientsandMethods:Weevaluated 75 children with genetically confirmedPWS,ofwhom50 fulfilled the criteria and were admitted to our study. The patients were evaluated before treatment (t0), after 6 weeks (t1), after 6 months (t2), after 12 months (t3), and yearly (t4-t6) thereafter, for up to 4 years of GH therapy. The central apnea index, obstructive apnea hypopnea index (OAHI), respiratory disturbance index, and minimal blood oxygen saturation were evaluated overnight using polysomnography. We evaluated the adenotonsillar size using a flexible fiberoptic endoscope. Results: The percentage of patients with an OAHI of 1 increased from 3 to 22, 36, and 38 at t1, t4, and t6, respectively (2 12.2; P .05). We observed a decrease in the respiratory disturbance indexfrom1.4 (t0) to 0.8 (t3) (P.05)andthe centralapneaindexfrom1.2 (t0) to 0.1 (t4) (P.0001). We had to temporarily suspend treatment for 3 patients at t1, t4, and t5 because of severe obstructive sleep apnea. The percentage of patients with severe adenotonsillar hypertrophy was significantly higher at t4 and t5 than at t0. The OAHI directly correlated with the adenoid size (adjusted for age) (P .01) but not with the tonsil size and IGF-1 levels. Conclusion: Long-termGHtreatment in patients withPWSis safe; however,werecommend annual polysomnography and adenotonsillar evaluation

Mutation profile of BBS genes in patients with Bardet-Biedl syndrome : An Italian study

Background: Bardet-Biedl syndrome (BBS) is a rare inherited multisystemic disorder with autosomal recessive or complex digenic triallelic inheritance. There is currently no treatment for BBS, but some morbidities can be managed. Accurate molecular diagnosis is often crucial for the definition of appropriate patient management and for the development of a potential personalized therapy. Methods: We developed a next-generation-sequencing (NGS) protocol for the screening of the 18 most frequently mutated genes to define the genotype and clarify the mutation spectrum of a cohort of 20 BBS Italian patients. Results: We defined the causative variants in 60% of patients; four of those are novel. 33% of patients also harboured variants in additional gene/s, suggesting possible oligogenic inheritance. To explore the function of different genes, we looked for correlations between genotype and phenotype in our cohort. Hypogonadism was more frequently detected in patients with variants in BBSome proteins, while renal abnormalities in patients with variations in BBSome chaperonin genes. Conclusions: NGS is a powerful tool that can help understanding BBS patients' phenotype through the identification of mutations that could explain differences in phenotype severity and could provide insights for the development of targeted therapy. Furthermore, our results support the existence of additional BBS loci yet to be identified