Cortisone and cortisol break hydrogen-bonding rules to make a drug-prodrug solid solution.

Multidrug products enable more effective therapies and simpler administration regimens, provided that a stable formulation is prepared, with the desired composition. In this view, solid solutions have the advantage of combining the stability of a single crystalline phase with the potential of stoichiometry variation of a mixture. Here a drug-prodrug solid solution of cortisone and cortisol (hydrocortisone) is described. Despite the structural differences of the two components, the new phase is obtained both from solution and by supercritical CO2 assisted spray drying. In particular, to enter the solid solution, hydrocortisone must violate Etter's rules for hydrogen bonding. As a result, its dissolution rate is almost doubled.

Harmful algal bloom forecast system for SW Ireland. Part I: Description and validation of an operational forecasting model.

A 3D primitive equation coastal ocean model for southwest Ireland, called the Bantry Bay model, was developed and implemented operationally. Validated model outputs have multiple uses. One of the incentives to develop the model was to explore the possible transport pathways that carry harmful algae blooms (HAB) into Bantry Bay. The model is nested offline in a regional North East Atlantic operational model. Surface forcing is taken from the half-degree Global Forecasting System, available at three-hourly intervals. Heat fluxes are calculated from the bulk formulae. Surface freshwater fluxes are obtained from the prescribed rainfall rates and the evaporation rates calculated by the model. Freshwater discharges from five rivers are included in the model. Model validation and the model skill in representing the water level, currents, temperature and salinity in the bay are reported. A scoring system based on the average adjusted relative mean absolute error for the predicted currents was used. An upgrade to a higher score was achieved through the incorporation of local winds into the surface forcing and by varying the bottom roughness coefficient. The model, designed to work in forecast mode, can replicate the main oceanographic features in the region. The model forecast is used in a decision support system for HAB alerts. An operational HAB alert system did not exist in Ireland prior to the use of this model.

Harmful algal bloom forecast system for SW Ireland. Part II: Are operational oceanographic models useful in a HAB warning system.

This study investigated the application of a three-dimensional physical hydrodynamic model in a harmful algal bloom forecast system for Bantry Bay, southwest Ireland. Modelled oceanographic conditions were studied and used to help understand observed changes in the chemical and biological patterns from the national biotoxins and phytoplankton monitoring program. The study focused on two toxic events in 2013. An upwelling event was predicted by the model prior to the appearance and population increase of potentially toxic diatoms, Pseudo-nitzschia, and associated domoic acid in shellfish. A downwelling episode was provided as a forecast in the model prior to the arrival of a Dinophysis bloom and detection of its associated biotoxins in Bay shellfish. The modelled forecast products developed included expected surface, mid-depth and bottom current pathways at the mouth of the Bay and on the adjacent shelf. The rate and direction of water volume flow at the mouth and mid-bay sections were produced by the model to examine predicted upwelling and downwelling pulses. The model also calculated the evolution of water properties (temperature, salinity and density) with depth along the Bay axis and on the adjacent continental shelf. Direct measurements of water properties at a fixed point, mid-bay, were comparable to model calculations. The operational model for southwest Ireland produces a reliable 3-day physical hydrodynamic forecast of the dominant regional physical processes that result in water exchange events between Bantry Bay and its adjacent shelf. While simulated physical hydrodynamics were provided as a 3-day forecast, the upwelling and downwelling signals from the model, closely linked to toxic HAB episodes, were evident up to 10 days prior to the contamination of shellfish in the Bay.

Risk factors associated with increased mortality of farmed Pacific oysters in Ireland during 2011.

The Pacific oyster, Crassostrea gigas, plays a significant role in the aquaculture industry in Ireland. Episodes of increased mortality in C. gigas have been described in many countries, and in Ireland since 2008. The cause of mortality events in C. gigas spat and larvae is suspected to be multifactorial, with ostreid herpesvirus 1 (OsHV-1, in particular OsHV-1µvar) considered a necessary, but not sufficient, cause. The objectives of the current study were to describe mortality events that occurred in C. gigas in Ireland during the summer of 2011 and to identify any associated environmental, husbandry and oyster endogenous factors. A prospective cohort study was conducted during 2010-2012, involving 80 study batches, located at 24 sites within 17 bays. All 17 bays had previously tested positive for OsHV-1µvar. All study farmers were initially surveyed to gather relevant data on each study batch, which was then tracked from placement in the bay to first grading. The outcome of interest was cumulative batch-level mortality (%). Environmental data at high and low mortality sites were compared, and a risk factor analysis, using a multiple linear regression mixed effects model, was conducted. Cumulative batch mortality ranged from 2% to 100% (median=16%, interquartile range: 10-34%). The final multivariable risk factor model indicated that batches imported from French hatcheries had significantly lower mortalities than non-French hatcheries; sites which tested negative for OsHV-1µvar during the study had significantly lower mortalities than sites which tested positive and mortalities increased with temperature until a peak was reached. There were several differences between the seed stocks from French and non-French hatcheries, including prior OsHV-1µvar exposure and ploidy. A range of risk factors relating to farm management were also considered, but were not found significant. The relative importance of prior OsHV-1µvar infection and ploidy will become clearer with ongoing selection towards OsHV-1µvar resistant oysters. Work is currently underway in Ireland to investigate these factors further, by tracking seed from various hatchery sources which were put to sea in 2012 under similar husbandry and environmental conditions.

The oil spill model OILTRANS and its application to the Celtic Sea.

This paper describes details of an oil spill model, OILTRANS, developed by the authors. The model is an off-line particle-transport model coupled to the most up to date operational met-ocean model forecasts. Formulations for the dominant oil fate processes of spreading, advection, diffusion, evaporation, emulsification and dispersion have been encoded, providing the model with the ability to accurately predict the horizontal movement of surface oil slick, the vertical entrainment of oil into the water column and the mass balance of spilled oil. The application of the OILTRANS model to an accidental release during a ship-to-ship fuel transfer in the Celtic Sea in February 2009 is presented to validate the system. Comparisons with aerial observations of the oil slick at the time of the incident, and subsequent model simulations, indicate that the OILTRANS model is capable of accurately predicting the transport and fate of the oil slick.