Growth parameters in children with achondroplasia: A 7-year, prospective, multinational, observational study.

PURPOSE: This study was undertaken to collect baseline growth parameters in children with achondroplasia who might enroll in interventional trials of vosoritide, and to establish a historical control. METHODS: In this prospective, observational study, participants (≤17 years) underwent a detailed medical history and physical examination and were followed every 3 months until they finished participating in the study by enrolling in an interventional trial or withdrawing. RESULTS: A total of 363 children were enrolled (28 centers, 8 countries). Mean (SD) follow up was 20.4 (15.0) months. In participants <1 year, mean annualized growth velocity (AGV) was 11.6 cm/year for girls and 14.6 cm/year for boys. By age 1 year, mean AGV decreased to 7.4 cm/year in girls and 7.1 cm/year in boys. By age 10 years, mean AGV decreased to 3.6 cm/year for both sexes. Mean height z-score in participants <1 year was -2.5 for girls and -3.2 for boys and decreased up to the age 5 years (-5.3 for girls; -4.6 for boys). Girls and boys had a disproportionate upper-to-lower body segment ratio. Mean ratio was highest in participants aged <1 year (2.9 for girls; 2.8 for boys) and decreased gradually to approximately 2 in both sexes from 4 years of age onward. CONCLUSION: This study represents one of the largest datasets of prospectively collected medical and longitudinal growth data in children with achondroplasia. It serves as a robust historical control to measure therapeutic interventions against and to further delineate the natural history of this condition.

International Otology Outcome Group and the International Consensus on the Categorization of Tympanomastoid Surgery.

The International Otology Outcome Group (IOOG) was founded in 2017 to encourage and facilitate international collaboration with regard to the surgical outcome of ear surgery. This report outlines the methodology and recommendations of the consensus-based categorization of tympanomastoid surgery produced by the IOOG. The IOOG Steering Committee used the acronym SAMEO-ATO to categorize tympanomastoid operations, representing the stage of surgery, approach, mastoid bone extirpation, external bony wall repair, obliteration of the mastoid cavity, access to the middle ear, tympanic membrane reconstruction, and ossicular reconstruction. A modified Delphi technique was used to obtain international consensus. The expert panels included the chairpersons from 21 otology societies. The approval rate of the SAMEO-ATO system from the otology societies was 95%. The SAMEO-ATO scheme was presented at the 31st Politizer Meeting for field testing. There were no objections or serious concerns raised. Some international otologists wished to see more surgical categories included to reflect the varieties of surgical techniques, but they accepted that it would make the whole system cumbersome. In addition to providing an international categorization of tympanomastoid surgery, the IOOG Steering Committee plans to introduce a common otology dataset that the international otology community could use to record their surgical outcome. The high level of international consensus on the IOOG categorization of tympanomastoid surgery supports this tool for surgeons to pool their surgical data into a large database for research and comparative audit.

Modeling competitive adsorption of mixtures of volatile organic compounds in a fixed-bed of beaded activated carbon.

A two-dimensional mathematical model was developed to study competitive adsorption of n-component mixtures in a fixed-bed adsorber. The model consists of an isotherm equation to predict adsorption equilibria of n-component volatile organic compounds (VOCs) mixture from single component isotherm data, and a dynamic adsorption model, the macroscopic mass, energy and momentum conservation equations, to simulate the competitive adsorption of the n-components onto a fixed-bed of adsorbent. The model was validated with experimentally measured data of competitive adsorption of binary and eight-component VOCs mixtures onto beaded activated carbon (BAC). The mean relative absolute error (MRAE) was used to compare the modeled and measured breakthrough profiles as well as the amounts of adsorbates adsorbed. For the binary and eight-component mixtures, the MRAE of the breakthrough profiles was 13 and 12%, respectively, whereas, the MRAE of the adsorbed amounts was 1 and 2%, respectively. These data show that the model provides accurate prediction of competitive adsorption of multicomponent VOCs mixtures and the competitive adsorption isotherm equation is able to accurately predict equilibrium adsorption of VOCs mixtures.

Two-dimensional modeling of volatile organic compounds adsorption onto beaded activated carbon.

A two-dimensional heterogeneous computational fluid dynamics model was developed and validated to study the mass, heat, and momentum transport in a fixed-bed cylindrical adsorber during the adsorption of volatile organic compounds (VOCs) from a gas stream onto a fixed bed of beaded activated carbon (BAC). Experimental validation tests revealed that the model predicted the breakthrough curves for the studied VOCs (acetone, benzene, toluene, and 1,2,4-trimethylbenzene) as well as the pressure drop and temperature during benzene adsorption with a mean relative absolute error of 2.6, 11.8, and 0.8%, respectively. Effects of varying adsorption process variables such as carrier gas temperature, superficial velocity, VOC loading, particle size, and channelling were investigated. The results obtained from this study are encouraging because they show that the model was able to accurately simulate the transport processes in an adsorber and can potentially be used for enhancing absorber design and operation.

Adsorption and desorption of mixtures of organic vapors on beaded activated carbon.

In this study, adsorption and desorption of mixtures of organic compounds commonly emitted from automotive painting operations were experimentally studied. A mixture of two alkanes and a mixture of eight organic compounds were adsorbed onto beaded activated carbon (BAC) and then thermally desorbed under nitrogen. Following both adsorption and regeneration, samples of the BAC were chemically extracted. Gas chromatography-mass spectrometry (GC-MS) was used to quantify the compounds in the adsorption and desorption gas streams and in the BAC extracts. In general, for both adsorbate mixtures, competitive adsorption resulted in displacing low boiling point compounds by high boiling point compounds during adsorption. In addition to boiling point, adsorbate structure and functionality affected adsorption dynamics. High boiling point compounds such as n-decane and 2,2-dimethylpropylbenzene were not completely desorbed after three hours regeneration at 288 °C indicating that these two compounds contributed to heel accumulation on the BAC. Additional compounds not present in the mixtures were detected in the extract of regenerated BAC possibly due to decomposition or other reactions during regeneration. Closure analysis based on breakthrough curves, solvent extraction of BAC and mass balance on the reactor provided consistent results of the amount of adsorbates on the BAC after adsorption and/or regeneration.

Effect of adsorption and regeneration temperature on irreversible adsorption of organic vapors on beaded activated carbon.

This paper investigates the effect of adsorption and regeneration temperature on the irreversible adsorption of a mixture of organic compounds typically emitted from automobile painting operations. Adsorption of the organic vapors mixture onto microporous beaded activated carbon (BAC) and regeneration of the saturated BAC were completed under different conditions. Results indicated that increasing the adsorption temperature from 25 to 35 or 45 °C increased heel buildup on BAC by about 30% irrespective of the regeneration temperature due to chemisorption. The adsorption capacity (for the first cycle) of the mixture onto the BAC at these three temperatures remained almost unchanged indicating chemisorption of some of these compounds onto the BAC. Increasing the regeneration temperature from 288 to 400 °C resulted in 61% reduction in the heel at all adsorption temperatures, possibly due to desorption of chemicals from narrow micropores. BET area and pore volumes of the BAC decreased proportionally to the cumulative heel. Pore size distribution and pore volume reduction confirmed that the heel was mainly built up in narrow micropores which can be occupied or blocked by some of the adsorbates.

Sleep-related disordered breathing in children with syndromic craniosynostosis.

BACKGROUND: Syndromic craniosynostosis patients are at risk for sleep-related disordered breathing (SRDB) but the role of polysomnography (PSG) in assessing these patients has not been fully explored. Our aim was to evaluate the prevalence or severity of SRDB in children with syndromic craniosynostosis or the impact of treatments on their SRDB. METHODS: We conducted a retrospective review of all patients with syndromic craniosynostosis referred between 1996 or 2008 for an initial PSG to rule out SRDB. For those with SRDB, we reviewed the interventions post PSG. RESULTS: 35 patients (18 females) were included. Specific diagnoses were Crouzon's (n=18), Apert's (n=14), Pfeiffer (n=2) or Saethre-Chotzen (n=1) syndromes. Their mean age was 4.5 years or their mean body mass index (BMI) was 16.9 kg/m(2). Of these patients, 26/35 (74%) had evidence of SRDB. The median obstructive apnoea index was 6.6/h (range 0.5-36.4/h) or median central apnoea index was 1.0/h (range 0.0-66.4/h). A total of 16 children had interventions to treat SRDB, of which 14/16 had a follow up PSG or only 10/14 (x%) had a significant improvement of their SRDB. CONCLUSION: This review confirms a high prevalence SRDB in this referred population. Despite various interventions, complete resolution of SRDB could not be achieved.

Kinetics and specificity of feline leukemia virus subgroup C receptor (FLVCR) export function and its dependence on hemopexin.

The feline leukemia virus subgroup C receptor (FLVCR) is a heme export protein that is required for proerythroblast survival and facilitates macrophage heme iron recycling. However, its mechanism of heme export and substrate specificity are uncharacterized. Using [(55)Fe]heme and the fluorescent heme analog zinc mesoporphyrin, we investigated whether export by FLVCR depends on the availability and avidity of extracellular heme-binding proteins. Export was 100-fold more efficient when the medium contained hemopexin (K(d) < 1 pm) compared with albumin (K(d) = 5 nm) at the same concentration and was not detectable when the medium lacked heme-binding proteins. Besides heme, FLVCR could export other cyclic planar porphyrins, such as protoporphyrin IX and coproporphyrin. However, FLVCR has a narrow substrate range because unconjugated bilirubin, the primary breakdown product of heme, was not transported. As neither protoporphyrin IX nor coproporphyrin export improved with extracellular hemopexin (versus albumin), our observations further suggest that hemopexin, an abundant protein with a serum concentration (6.7-25 mum) equivalent to that of the iron transport protein transferrin (22-31 mum), by accepting heme from FLVCR and targeting it to the liver, might regulate macrophage heme export and heme iron recycling in vivo. Final studies show that hemopexin directly interacts with FLVCR, which also helps explain why FLVCR, in contrast to some major facilitator superfamily members, does not function as a bidirectional gradient-dependent transporter. Together, these data argue that hemopexin has a role in assuring systemic iron balance during homeostasis in addition to its established role as a scavenger during internal bleeding or hemolysis.