Hydrocortisone granules are bioequivalent when sprinkled onto food or given directly on the tongue

Background Immediate-release hydrocortisone granules in capsules for opening in paediatric appropriate doses have recently been licensed for children with adrenal insufficiency. This study evaluated the bioavailability of hydrocortisone granules administered as sprinkles onto soft food and yoghurt compared to direct administration to the back of the tongue. Methods Randomised, three-period crossover study in 18 dexamethasone-suppressed healthy men. In each period the fasted participants received hydrocortisone granules 5mg either directly to the back of the tongue, or sprinkled onto soft food (applesauce), or yoghurt, followed by 240mL of water. Serum cortisol was measured by LC-MS/MS. Results The cortisol geometric mean Cmax and AUC for direct administration, sprinkles onto yoghurt, and sprinkles onto soft food were: Cmax 428, 426, 427 nmol/L & AUC0-inf 859, 886, 844 h*nmol/L, & AUC0-t 853, 882, 838 h*nmol/L respectively. The 90% confidence intervals (CI) for the ratios of Cmax, AUC0-inf & AUC0-t for administration with soft food or yoghurt to direct administration were well within the bioequivalent range, 80-125%. Median Tmax was similar between methods of administration: 0.63h administered directly, 0.75h on soft food and 0.75h on yoghurt. No adverse events occurred during the study. Conclusions Hydrocortisone granules administered as sprinkles onto soft food or yoghurt but not mixed with are bioequivalent to those administered directly to the back of the tongue. Carers, parents or patients may choose to administer hydrocortisone granules either directly or sprinkled onto soft food or yoghurt

Alcohol-related emergency department presentations and hospital admissions around the time of minimum unit pricing in Ireland

Background Minimum unit pricing (MUP) was recently introduced in Ireland to reduce alcohol-related harms. The size of the impact of alcohol on hospital emergency departments (EDs) in Ireland is poorly understood due to inconsistent alcohol screening and documentation. Aims We sought to systematically characterise the volume, timing, and nature of alcohol-related presentations and admissions to a busy urban ED in Dublin, Ireland. Method Patients presenting to the ED were assessed by a dedicated clinician during selected time periods before (Nov–Dec 2021) and after (Feb–Apr 2022) the introduction of MUP. A total of 725 interviews were conducted over 168 h in the ED. Findings Alcohol consumption was a factor in 19.4% of ED presentations and in 17.3% of hospital admissions across the entire study period. A reduction in overall alcohol-related ED presentations was noted in the period following MUP, although it is not possible to conclude a direct effect. Conclusion Alcohol-related harm places a significant strain on EDs and hospitals, and the impact of MUP on hospital burden in Ireland merits further evaluation. Effective measures at local and population levels are urgently required to address this burden

Investigation of coastal sea-fog formation using the WIBS (wideband integrated bioaerosol sensor) technique

A wideband integrated bioaerosol sensor (WIBS-4) was deployed in Haulbowline Island, Cork Harbour, to detect fluorescence particles in real time during July and September 2011. A scanning mobility particle sizer (SMPS) was also installed providing sizing analysis of the particles over the 10–450&thinsp;nm range. During the campaign, multiple fog formation events occurred; they coincided with dramatic increases in the recorded fluorescent particle counts. The WIBS sizing and fluorescence intensity profiles indicated that the origin of the signals was potentially non-biological in nature (i.e. PBAPs, primary biological aerosol particles). Furthermore, the data did not support the presence of known fluorescing chemical particles like SOA (secondary organic aerosol). Complementary laboratory studies showed that the field results could potentially be explained by the adsorption of molecular iodine onto water droplets to form I2&thinsp;⋅&thinsp;(H2O)x complexes. The release of iodine into the coastal atmosphere from exposed kelp at low tides has been known for many years. This process leads to the production of small IxOy particles, which can act as cloud condensation nuclei (CCN). While the process of molecular iodine release from coastal kelp sources, subsequent particle formation, and the observations of sea mists and fogs have been studied in detail, this study provides a potential link between the three phenomena. Of mechanistic interest is the fact that molecular iodine included into (rather than on) water droplets does not appear to fluoresce as measured using WIBS instrumentation. The study indicates a previously unsuspected stabilizing transport mechanism for iodine in the marine environment. Hence the stabilization of the molecular form would allow its more extensive distribution throughout the troposphere before eventual photolysis.</p

Ultra-low DNA input into whole genome methylation assays and detection of oncogenic methylation and copy number variants in circulating tumour DNA

Background: Abnormal CpG methylation in cancer is ubiquitous and generally detected in tumour specimens using a variety of techniques at a resolution encompassing single CpG loci to genome wide coverage. Analysis of samples with very low DNA inputs, such as formalin fixed (FFPE) biopsy specimens from clinical trials or circulating tumour DNA is challenging at the genome-wide level because of lack of available input. We present the results of low input experiments into the Illumina Infinium HD methylation assay on FFPE specimens and ctDNA samples. Methods: For all experiments, the Infinium HD assay for methylation was used. In total, forty-eight FFPE specimens were used at varying concentrations (lowest input 50 ng); eighteen blood derived specimens (lowest input 10 ng) and six matched ctDNA input (lowest input 10 ng)/fresh tumour specimens (lowest input 250 ng) were processed. Downstream analysis was performed in R/Bioconductor for quality control metrics and differential methylation analysis as well as copy number calls. Results: Correlation coefficients for CpG methylation were high at the probe level averaged R2 = 0.99 for blood derived samples and R2 > 0.96 for the FFPE samples. When matched ctDNA/fresh tumour samples were compared, R2 > 0.91 between the two. Results of differential methylation analysis did not vary significantly by DNA input in either the blood or FFPE groups. There were differences seen in the ctDNA group as compared to their paired tumour sample, possibly because of enrichment for tumour material without contaminating normal. Copy number variants observed in the tumour were generally also seen in the paired ctDNA sample with good concordance via DQ plot. Conclusions: The Illumina Infinium HD methylation assay can robustly detect methylation across a range of sample types, including ctDNA, down to an input of 10 ng. It can also reliably detect oncogenic methylation changes and copy number variants in ctDNA. These findings demonstrate that these samples can now be accessed by methylation array technology, allowing analysis of these important sample types