Clinical trial management: a profession in crisis?

Clinical trial managers play a vital role in the design and conduct of clinical trials in the UK. There is a current recruitment and retention crisis for this specialist role due to a complex set of factors, most likely to have come to a head due to the COVID-19 pandemic. Academic clinical trial units and departments are struggling to recruit trial managers to vacant positions, and multiple influences are affecting the retention of this highly skilled workforce. Without tackling this issue, we face major challenges in the delivery on the Department of Health and Social Care's Future of UK Clinical Research Delivery implementation plan. This article, led by a leading network of and for UK Trial Managers, presents some of the issues and ways in which national stakeholders may be able to address this.

An angled insertion technique using 6-mm needles markedly reduces the risk of intramuscular injections in children and adolescents.

AIMS: The aims of this study were (i) to establish which children with Type 1 diabetes are at risk of intramuscular or intradermal insulin injections and (ii) to determine a needle length and technique that reliably administers insulin into subcutaneous fat. METHODS: Seventy-two healthy diabetic children (age 6.3-14.3 years, body mass index standard deviation score 1.0 +/- 1.4) were recruited for study 1 and 37 of this cohort participated in study 2. In study 1, 200 microl air was injected into the abdomen and anterior thigh by a pinched skin-fold technique using either a perpendicular insertion of NovoFine(R) 31G 6-mm or an angled insertion of NovoFine(R) 30G 8-mm needles. In study 2, subjects received injections into abdomen and anterior thigh via angled 6-mm needles with either an unpinched or pinched technique. The site of air injection was visualized by ultrasound scan and measurements taken of subcutaneous fat thickness. RESULTS: In study 1, intramuscular injections were detected in 32% of subjects, and in a further 22% air was visualized at the muscle fascia. In study 2, intramuscular injections occurred in 3% of subjects and a further 11% had muscle fascia air detected. No intramuscular injections occurred in subjects injecting with a 6-mm needle and an angled pinched skin-fold technique. Pinching abdomen and thigh skin folds increased the subcutaneous fat thickness by 192 +/- 16% and 22 +/- 6%, respectively. In very lean subjects, pinching thighs actually reduced subcutaneous fat thickness. CONCLUSIONS: While intramuscular injections were observed frequently using standard injection protocols, an angled 6-mm needle technique reliably injects into the subcutaneous fat.

The role of blue copper proteins in the oxidation of methylamine by an obligate methylotroph.

Organism 4025, an obligate methylotroph, when grown on methylamine in the presence of a high concentration of copper, contained high concentrations of methylamine dehydrogenase and two blue copper proteins, amicyanin and an azurin-type protein; these were purified to homogeneity and characterized. The methylamine dehydrogenase is a basic protein (pI 8.8) and consists of light and heavy subunits (Mr 14100 and 43000; total Mr 112000). This dehydrogenase differed slightly from other methylamine dehydrogenases in its absorption spectrum and in its lack of thermal stability. Amicyanin, the more abundant blue copper protein, had an Mr of 11500, a midpoint redox potential of 294mV at pH 7.0, and a much lower isoelectric point (pI5.3) than other amicyanins. Its absorption maximum was 620 nm (7-24 nm higher than those of other amicyanins); its absorption coefficient (at 620 nm) was 3.8 mM-1 X cm-1. The 'azurin' (6% of the blue copper protein) had an Mr of 12500, a midpoint redox potential of 323 mV and a high isoelectric point (pI 9.4). Its absorption maximum was 620 nm, the absorption coefficient (16 mM-1 X cm-1) at this wavelength being considerably greater than that of any blue copper protein described previously. The partially-purified soluble cytochromes cH and cL were similar to those of other methylotrophs. The interactions of the purified redox proteins were investigated in order to elucidate their role in methylamine oxidation. Methylamine dehydrogenase was able to donate electrons only to amicyanin, the rate of reaction being 2.04 mmol/min per mumol of methylamine dehydrogenase; this is sufficient to account for the rate of respiration in whole bacteria. The blue copper proteins were able to react rapidly with each other and with both the soluble cytochromes c.

Absolute measurements of absorption at the iodine-laser frequency in atmospheric gases.

The absorption cross sections at the chemical-iodine-laser frequency for methane and carbon dioxide in an atmosphere of dry air were determined with a photoacoustic cell to be (8 +/- 2) x 10(-24) and (5.4 +/- 0.4) x 10(-25) cm(2), respectively. A multipass absorption cell and a Fourier-transform spectrometer were used to obtain a cyclopropane absorption cross section of (3.47 +/- 0.02) x 10(-24) cm(2) at 14 076 cm(-1) for the photoacoustic-cell calibration.