Sex assignment in conditions affecting sex development

The newborn infant with atypical genitalia presents a challenging clinical scenario and requires expert input. There have been appreciable advances in our knowledge of the underlying causes that may lead to a mere difference or a more serious disorder of sex development (DSD), the natural history of conditions, as well as the short and long-term complications of these conditions themselves, together with the clinical interventions that are associated with these conditions. With this information, the DSD expert can be more confident when discussing options with the parents of the newborn infant. By working within a multidisciplinary team, the expert should be able to support the family whilst individualising the management plan so that it is also cognizant of the shifts in societal attitudes and expectations around concepts of diversity and openness. It is, therefore, likely that the practice of assigning sex, especially in those cases where sex assignment is unclear on expert assessment, will continue to show temporal, social and geographical variations. It is imperative that clinical data for rare conditions such as these are collected in a standardized format and shared through a common registry so that any evidence that is used for future shifts in practice has a stronger foundation than that which is currently available

High order fluid model for streamer discharges. II. Numerical solution and investigation of planar fronts

The high order fluid model developed in the preceding paper is employed here to study the propagation of negative planar streamer fronts in pure nitrogen. The model consists of the balance equations for electron density, average electron velocity, average electron energy and average electron energy flux. These balance equations have been obtained as velocity moments of Boltzmann's equation and are here coupled to the Poisson equation for the space charge electric field. Here the results of simulations with the high order model, with a PIC/MC (Particle in cell/Monte Carlo) model and with the first order fluid model based on the hydrodynamic drift-diffusion approximation are presented and compared. The comparison with the MC model clearly validates our high order fluid model, thus supporting its correct theoretical derivation and numerical implementation. The results of the first order fluid model with local field approximation, as usually used for streamer discharges, show considerable deviations. Furthermore, we study the inaccuracies of simulation results caused by an inconsistent implementation of transport data into our high order fluid model. We also demonstrate the importance of the energy flux term in the high order model by comparing with results where this term is neglected. Finally, results with an approximation for the high order tensor in the energy flux equation is found to agree well with the PIC/MC results for reduced electric fields up to 1000 Townsend, as considered in this work.Comment: 26 pages, 11 figure

PGE2 Receptor Subsets Mediate HCG Regulation of the Plasminogen Activator/Plasmin System in Primate Periovulatory Follicles

Elevated follicular prostaglandin E2 (PGE2) levels are necessary for follicle rupture during ovulation. As the degradation of the follicle wall requires proteolysis, it was hypothesized that regulation of proteolysis by gonadotropins is PGE2 mediated. There are four PGE2 receptors: EP1, EP2, EP3 and EP4. To determine which PGE2 receptors are present in monkey periovulatory follicles, granulosa cells and whole ovaries were collected 0, 12, 24, and 36 hours after administration of an ovulatory dose of human chorionic gonadotropin (hCG), or 36 hours after hCG from monkeys that received the prostaglandin (PG) synthesis inhibitor celecoxib. All EP receptor mRNAs were present in granulosa cells. By immunofluorescence, EP1 was detectable only 36 hours after hCG. EP2 and EP3 proteins were present throughout the periovulatory interval. By western blotting, EP2 and EP3 proteins increased between 0 and 36 hours after hCG. EP4 protein was not detected in periovulatory granulosa cells. An increase in EP2 and EP3 receptor responsiveness was confirmed by measuring elevated cAMP levels in response to receptor selective agonists. EP1 receptor function, measured as an increase in intracellular calcium, was present only 36 hours after hCG administration. To elucidate the role of the ovulatory gonadotropin surge and PGs in the regulation of periovulatory proteolytic events, the expression of mRNA and protein for the tissue type plasminogen activator (tPA) and urokinase type plasminogen activator (uPA) and their inhibitor PAI-1 was measured in granulosa cells. uPA and PAI-1 mRNAs peaked 12 hours and 36 hours after hCG administration respectively. tPA mRNA decreased 36 hours after hCG. Celecoxib administration had no effect on any of these mRNAs. By immunofluorescence, tPA and PAI-1 protein expression increased 12 hours after hCG and persisted until 36 hours after hCG. tPA and PAI-1 proteins were not detectable 36 hours after hCG in celecoxib treated animals. uPA was not detectable in granulosa cells before and after hCG administration. By in situ zymography, plasminogen activator (PA) activity was low before hCG administration and detectable 12, 24 and 36 hours after hCG. PA activity was attenuated by pre-incubation with an anti-tPA antibody. Animals treated for 36 hours with hCG+celecoxib had low ovarian PA activity. To determine whether PGE2 is the key PG in the regulation of PA family members, 0 hour granulosa cells were hCG treated with or without PGE2 or EP receptor selective agonists. tPA protein increased only in the presence of PGE2, the EP2 agonist or the EP3 agonist. PAI-1 protein was detected in cells cultured with PGE2, the EP1 agonist or the EP3 agonist. These studies demonstrate that the ovulatory gonadotropin stimulates granulosa cell EP receptor expression and responsiveness. PGE2, acting through EP2 and EP3 receptors, may mediate the hCG induced increase in tPA proteolytic activity. Taken together, this study elucidates the mechanisms by which the ovulatory gonadotropin surge and PGE2 cooperate to regulate proteolysis in the periovulatory follicle. This information may lead to improved treatments for anovulation or to the development of new contraceptive options

Functional Foods in the Marketplace: Willingness to Pay for Apples Enriched with Antioxidants

The attention on so-called functional foods has been growing as consumers become more concerned with diet and nutrition. This article aims to measure consumers response to apples with naturally enriched antioxidant coatings. Surveys were conducted in grocery stores in Seattle, Washington and Spokane, Washington. The results suggest that consumers have a somewhat positive attitude towards functional foods in general and with apples enriched with antioxidants in particular. A contingent valuation technique was used to assess factors affecting consumers willingness to pay for the apples with antioxidant coatings. Consumers in the Spokane grocery stores are more likely to pay a premium for the new type of apples than consumers in Seattle. Consumers who look for a wide variety of product in choosing where to shop for food are more likely to pay a premium for apples enriched with antioxidants. Also, it is estimated that consumers, on average, are willing to pay from 4% to 8% premium for these apples.functional food, willingness to pay, antioxidants, Demand and Price Analysis, Health Economics and Policy,

Central Precocious Puberty as a Sign of Congenital Adrenal Hyperplasia: Case Presentations

Central precocious puberty results from the premature activation of the hypothalamic-pituitary-gonadal axis. Rarely congenital adrenal hyperplasia and/or its inappropriate treatment can be a peripheral cause of CPP. There are very few case reports of this etiology. Chronic mildly to moderately elevated adrenal androgens or intermittent hyperandrogenemia in congenital adrenal hyperplasia may trigger the precocious activation of the hypothalamic-pituitary axis, leading to CPP. In the current work, we describe 6 cases of late diagnosis of congenital adrenal hyperplasia associated with central precocious puberty. Central precocious puberty seems to be a complication of congenital adrenal hyperplasia, particularly in countries where a routine neonatal screening program for this condition is lacking. It is unclear whether these patients could avoid central precocious puberty development if the congenital adrenal hyperplasia was diagnosed in the neonatal period and appropriately treated. The current work underlines the need for congenital adrenal hyperplasia neonatal screening implementation and further investigation of the association of these two endocrine disorders

Comparison of single-layer and double-layer anti-reflection coatings using laser-induced damage threshold and photothermal common-path interferometry

The dielectric thin-film coating on high-power optical components is often the weakest region and will fail at elevated optical fluences. A comparison of single-layer coatings of ZrO2, LiF, Ta2O5, SiN, and SiO2 along with anti-reflection (AR) coatings optimized at 1064 nm comprised of ZrO2 and Ta2O5 was made, and the results of photothermal common-path interferometry (PCI) and a laser-induced damage threshold (LIDT) are presented here. The coatings were grown by radio frequency (RF) sputtering, pulsed direct-current (DC) sputtering, ion-assisted electron beam evaporation (IAD), and thermal evaporation. Test regimes for LIDT used pulse durations of 9.6 ns at 100 Hz for 1000-on-1 and 1-on-1 regimes at 1064 nm for single-layer and AR coatings, and 20 ns at 20 Hz for a 200-on-1 regime to compare the //ZrO2/SiO2 AR coating