Although glucocorticoid replacement is conventionally administered twice daily, the pharmacokinetics of hydrocortisone would predict very low levels of plasma cortisol by mid-afternoon. This study compared plasma cortisol day profiles in 7 hypoadrenal patients while on twice daily and thrice daily hydrocortisone replacement. The twice daily regimen was associated with very low levels of cortisol at 16.00 and 18.00 h. This was eliminated by administering the same total dose in a thrice daily regimen. Furthermore, estimates of 'well-being' by visual analogue scale correlated significantly with simultaneous plasma cortisol levels and 5 of the patients expressed a preference for the thrice daily regimen. The findings suggest that thrice daily glucocorticoid replacement therapy should be adopted routinely.

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We describe a method for the design of multicyclic compounds from three-dimensional (3D) molecular fragments. The 3D building blocks are assembled in a controlled fashion, and closable chains of such fragments are identified. Next, the ring-closing conformations of such formally closable chains are identified, and the 3D model of a cyclic or multicyclic molecule is built. Embedding this method in an evolutionary algorithm results in a de novo design tool capable of altering the number and nature of cycles in species such as transition metal compounds with multidentate ligands in terms of, for example, ligand denticity, type and length of bridges, identity of bridgehead terms, and substitution pattern. An application of the method to the design of multidentate nitrogen-based ligands for Fe(II) spin-crossover (SCO) compounds is presented. The best candidates display multidentate skeletons new to the field of Fe(II) SCO yet resembling ligands deployed in other fields of chemistry, demonstrating the capability of the approach to explore structural variation and to suggest unexpected and realistic molecules, including structures with cycles not found in the building blocks.

Novel nanostructured sulfur (S)–carbide derived carbon (CDC) composites with ordered mesopores and high S content are successfully prepared for lithium sulfur batteries. The tunable pore‐size distribution and high pore volume of CDC allow for an excellent electrochemical performance of the composites at high current densities. A higher electrolyte molarity is found to enhance the capacity utilization dramatically and reduce S dissolution in S‐CDC composite cathodes during cycling.

The effect of different rates of potassium (K) fertilizer on the yield and quality of sugar beet was studied in a series of 26 trials on soils of different type and K index between 1992 and 1997. There were few yield responses even though the majority of trials were on soils of low K index, and large quantities of fertilizer were applied (0-600 kg K\ha). Potassium offtakes (kg\ha) in the harvested beet increased asymptotically, not linearly, with yield and were much larger for a given yield on high K index soils than on low index soils. Commercially acceptable concentrations of beet K for processing are in the range 700 to 1000 mg K\100 g sugar. Concentrations in excess of this decrease the amount of sugar crystallized from the extracted juice. They were not greatly affected by large applications of fertilizer K but were strongly influenced by long-established differences in soil exchangeable K (K ex ) due to soil type, previous cropping or manuring history.The asymptotic nature of the K offtake : yield relationship was confirmed by factory tarehouse measurements relating to the national sugar beet crop delivered during the 1993-97 UK processing campaigns. Potassium offtakes generally increased linearly with yield up to 60-70 adjusted t of clean beet\ha, but increased little beyond that. The amount of K removed by a 60-70 t\ha crop of beet varied from 70 kg K\ha on low K index sandy loams to 120 kg K\ha on clay soils of K index 3 and above. Further increases in yield decreased the amount of K in fresh beet from 1n7 to 1n4 kg K\t on low K index soils, and from 3n6 to 2n5 kg K\t on high K index soils.An analysis of data from individual fields of commercially grown sugar beet showed that much of the site and season variation in the K content of beet was due to differences in K uptake driven by K ex , and to differential effects of nitrogen (N) supply on K uptake and sugar yield. Regressions on K ex and total crop N (kg\ha) accounted for c. 30 and 50 % of the variance in beet K content, respectively, and the two together for over 60 %. Total N uptake by the crops ranged from 100 to 550 kg N\ha. The total K content of the crop and the amounts of K in the beet (kg\ha) both increased linearly with crop N over the whole of this range, whereas sugar yield increased asymptotically with total uptakes of N up to 250-300 kg N\ha. Consequently, low yielding crops grown on soils in which N and K were freely available produced beet of poor K quality. However, the asymptotic relationship between beet K (kg\ha) and yield implies that, in many situations, the processing quality of the beet could be improved by increasing yield through better agronomy.

The examination of the urinary deposit has long been accepted as a useful procedure in the diagnosis of renal disease. As usually performed, however, the value of the information that it affords is limited by the inaccuracy of the method employed, since the deposit derived from the untimed random sample of urine is not susceptible of quantitative study. This latter is essential, for example, in the diagnosis of chronic pyelonephritis, in which it is well known that, at least until renal destruction has become gross and renal failure is at hand, the urinary deposit is commonly small and inconstant. Repeated cultures may be necessary before a growth is obtained.In the course of an investigation of pyelonephritis we employed a method more sensitive than usual for the culture of urinary deposits, and, since this inevitably might have increased the frequency with which contaminant or saprophytic organisms appeared, we felt it necessary to check the significance of our cultural methods by attempting to correlate them with an accurate count of the cells excreted in the urine.The best-known method of quantitative estimation of the constituents of the urinary deposit is that of Addis (1925). This, however, seemed to us to suffer from various disadvantages. The method makes it necessary for female subjects, who have to be catheterized, to hold their urine for 12 hours. Moreover, the time over which the urine is collected allows a proportion of the cells in the urine to break up: this point is discussed below. Finally, the number of elements actually counted by the Addis technique is so small that it is multiplied by a factor of one million in order to arrive at the presumed excretion rate; errors of sampling and of counting thus figure largely in the final result.More recently, Rofe (1955) has described a method in which the leucocytes and epithelial cells excreted in the urine are counted after staining. We considered this method to be rather too elaborate to be suitable for routine use. It is the purpose of this paper to present a reliable, simple, and rapid method of counting the leucocytes and non-squamous epithelial cells in the urine. Although the primary purpose of this paper is to report the cell excretion in normal subjects, a few counts obtained from patients with renal infection are included. Of these patients those with the lower cell counts had deposits which by the usual method of examination showed little or no deviation from normal.The cellular excretion rates were determined as follows. The subject emptied the bladder as completely as possible and the time was carefully noted. Three to four hours later, the time again being noted, the bladder was emptied by catheter in the female, and naturally in the male, avoiding preputial contamination. No restrictions were placed on fluid intake, but diuretics were not given. The specimen obtained was measured, and within two hours of collection it was thoroughly shaken. Precipitated phosphates were dissolved by adding a few drops of glacial acetic acid, and 10 ml....

1. Activities of arginine synthetase system enzymes, alanine aminotransferase (AlT) and branched-chain amino acid transaminase (BATase) were measured in control and uraemic rats after 2 weeks on a free protein intake and after 10 days on a lowprotein diet.2. Protein restriction alone reduced the activity of all three enzymes. 3. Uraemia alone increased the activity of arginine synthetase system enzymes and AlT. BATase was not altered.4. After protein restriction the BATase activity in uraemic rats decreased to the same extent as in controls. The activity of arginine synthetase system enzymes and AlT were significantly higher than in protein-restricted controls and were the same as in control rats on a normal diet.5. Practical consequences of the finding that uraemia prevented the decrease of AlT but not of BATase activity in response to a low-protein diet are discussed, with particular reference to reutilization of urea-nitrogen for the synthesis of non-essential and essential amino acids.

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