Do we really know how many clinical trials are conducted ethically? Why research ethics committee review practices need to be strengthened and initial steps we could take to strengthen them

Research Ethics Committees (RECs) play a critical gatekeeping role in clinical trials. This role is meant to ensure that only those trials that meet certain ethical thresholds proceed through their gate. Two of these thresholds are that the potential benefits of trials are reasonable in relation to risks and that trials are capable of producing a requisite amount of social value. While one ought not expect perfect execution by RECs of their gatekeeping role, one should expect routine success in it. This article reviews a range of evidence showing that substantial numbers of ethically tainted trials are receiving REC approvals. Many of the trials are early phase trials that evidence shows have benefits that may not be reasonable compared with their risks and many others are later trials that evidence shows may lack sufficient social value. The evidence pertains to such matters as methodologically inadequate preclinical studies incapable of supporting the inferences that REC members must make about the prospects for potential benefit needed to offset the risks in early phase trials and sponsorship bias that can cause improperly designed, conducted, analysed and reported later phase trials. The analysis of the evidence makes clear that REC practices need to be strengthened if they are to adequately fulfil their gatekeeping role. The article also explores options that RECs could use in order to improve their gatekeeping function.

Picolitre-scale crystallization of membrane proteins

Crystallization of membrane proteins in lipidic mesophases by the standardin mesomethod is extremely efficient in that small amounts of valuable protein are required per trial. Here it is shown that it is possible to reduce the requisite amount of protein (and lipid) by two orders of magnitude into the picolitre volume range. Successful crystallizations have been performed with two integral membrane proteins, bacteriorhodopsin and the vitamin B12receptor, BtuB, using volumes of mesophase corresponding to 210 pl of protein solution (2–4 ng protein) and 320 pl of lipid. The total dead volume of the system is 1 µl. This means that thousands of crystallization trials can be performed with just micrograms of the target. Thus, for a given amount of protein, which is often in short supply, the likelihood of obtaining crystals is significantly enhanced. The reproducibility of crystallogenesis and of volume delivery at this picolitre scale is described. This advance will contribute to broadening the range of membrane proteins that yield to structure determination.

A Method for Planning and Performing a Pressure Survey to Achieve Desired Accuracy of Pressure Gradient

This paper describes a method for planning a pressure survey (a series of pressure, depth measurements), and for using a pressure survey tool, so that the user can predict in advance the number of pressure tests needed to be performed in a pressure survey such that the resulting pressure gradient will be accurate within a desired standard deviation. It further describes a method and process for performing a pressure survey, including measuring pressure gradient and standard deviation thereof for downhole fluid bearing formations, using information collected from pressure survey apparatus, such that the requisite amount of information is collected to ensure the measurements actually received are within the desired standard deviation. There is a patent pending in the U.S. Patent Office for the technology described herein.

Therapeutic properties of whey used as fermented drink

Bioconversion of whey for preparation of beverage was standardized by utilizing yoghurt cultures. The product, wheyghurt drink, made with 4% yoghurt cultures inoculated in deproteinized whey (4.8% lactose, 0.66% ash, 0.46% fat and 0.40% protein adjusted to pH 6.4) and incubated at 42oC for 8h had all the technological requisite and dietetic criteria required in the product. The factors affecting the antibacterial activity of wheyghurt drink against Escherichia coli, Staphylococcus aureus, Shigella dysenteriae and Bacillus cereus were determined. There was a significant variation (P<0.05) in the antibacterial activity of wheyghurt drink with different levels of inoculum (1,2,4, and 8%) and concentration of sugar at 37, 42 and 45oC. Incubation at 42oC with 4% culture in whey exhibited highest inhibitory activity. The product stored up to 5 days under refrigeration was of acceptable organoleptic quality and requisite amount of microbial population (108 cfu/ml) to be potentially beneficial.

The effects of dietary soybean oil on milk-fat composition in the cow

SummaryThe effects of the isocaloric replacement of starch in a low-fat concentrate mixture by 8% soybean oil on the yield and composition of milk fat were investigated in a feeding experiment with 6 cows in mid lactation. Two high-fat concentrate mixtures were given to the cows. In one the requisite amount of soybean oil was given by including 50% coarsely ground soybeans in the concentrate mixture. In the other an equal amount of soybean oil was added directly to the concentrate mixture. The concentrate mixtures were given with a high-roughage diet that supplied 5·5kg hay and 2·7kg of sugar-beet pulp/day.When the 2 high-fat rations were given to the cows there were reductions in the percentages and yields of 10:0, 12:0, 14:0, 14:1, 16:0 and 16:1 fatty acids and increases in the concentrations and yields of 18:0, 18:1 and 18:2 fatty acids in the milk fat. The direct addition of the soybean oil to the diet also reduced the percentage and yield of 6:0 and 8:0 whilst the inclusion of the soybeans increased the percentage of 4:0 and the yields of 4: 0 and 6:0 in the milk fat.When both high-fat rations were given to the cows there were increases in the yields and concentrations of as-9–18:1 in the milk fat, whilst inclusion of the soybean oil in the diet increased also the concentration and yield of trans-11–18:1.The implications of these findings are discussed.

A Slide Heater for Clearing Minute Insect Specimens

The use of potassium hydroxide solutions for clearing minute insect specimens, or portions of large ones, is a well-known and widely used procedure. Extreme care, however, is necessary to provide rapidly the exact degree of transparency in the subject. To provide for these requirements an economical heater was designed to warm a micro-culture slide bearing a few drops of clearing solution. The specimen is immersed in the cold solution on the slide, and the slide is then placed on the heater. The requisite amount of current is supplied to the heating element and clearing of the specimen to the exact degree desired can be obtained in a short time while the process is observed through a binocular dissecting microscope.

DIMETHYLDINITROÖXAMIDE

A practical low-cost method is described for the preparation of the explosive dimethyldinitroöxamide. Dimethyloxamide is prepared in 94% yield from an oxalic ester and methylamine, and then is nitrated in 98% yield with slightly more than the requisite amount of nitric acid. The nitrating acid can be recovered safely. The optimum yield is obtained when the waste acid has the composition sulphuric acid monohydrate.

The structure and activation of the phosgene molecule. Part II.—The Raman spectrum of phosgene

The vessel in which the phosgene was contained for illumination was a glass tube 3 cm. diameter and 10 cm. long, closed at one end and ending at the other in a “tail” bent at right angles. The tail had a bulb of about 25 c. c. capacity to allow for subsequent expansion of the liquid after filling at low temperature, and it was coated with black wax to prevent reflection from this end of the vessel. This Raman tube was filled in the following way. A stream of phosgene from a bomb (supplied by Messrs. Siegfried, of Zofingen) was led through a glass coil cooled in a freezing mixture of ice and salt. The condensed phosgene was received in a bulb of about 120 c. c. capacity cooled in ether and carbon dioxide ice. The bulb was joined to the Raman tube and a side tube was provided for evacuation. When a sufficient quantity of liquid had been collected, the receiving bulb was sealed off from the condenser coil, the two bulbs were evacuated through calcium chloride tubes by means of a water-pump and the side tube was sealed off. The Raman tube was then cooled in alcohol and carbon dioxide ice and the receiving bulb allowed to warm slowly, so that the phosgene distilled over quietly without ebullition. When the requisite amount was present, the tube was sealed off. The liquid produced in the initial condensation was somewhat cloudy but on redistillation into the Raman tube it was obtained perfectly clear.

Ionisation potentials of mercury, cadmium, and zinc, and the single- and many-lined spectra of these elements

In a paper by Frank and Hertz in the ‘Physikalische Zeitschrift,’ these investigators have shown that the minimum energy required to ionise an atom of mercury is that acquired by an electron in passing through a fall of potential of 4·9 volts. These writers have also shown in a later communication that when heated mercury vapour is traversed by electrons possessing energy slightly above this amount the vapour is stimulated to the emission of the single spectral line λ = 2536·72 Å. U. This result constitutes a new and most interesting application of the quantum theory, for it will be seen that in the relation V e = hv , where h = 6·6 x 10 -27 erg sec. 4·9 volts is the potential fall which corresponds to the frequency v of the line λ = 2636·72 Å. U. If the relation just pointed out be applicable generally to all the elements it follows that if the vapour of an element can be shown to be capable of exhibiting a single-line spectrum, the frequency of this single spectral line may be used to deduce the minimum amount of energy required to ionise the atoms of that element. With the object of establishing such a generalisation, if possible, some experiments were recently made by the writers, and it has been found that the vapours of cadmium and zinc as well as that of mercury can be stimulated to the emission of single-line spectra when traversed by electrons possessing the requisite amount of energy. With cadmium vapour the wave-length of the line constituting this single-line spectrum is λ = 3260·17 Å. U., while that of the single-line spectrum of zinc vapour is λ = 3075·99 Å. U. By the quantum theory it follows then that the minimum ionising potential for cadmium and zinc vapours are respectively 3·74 volts and 3·96 volts.

I.—Eminent Living Geologists

William Boyd Dawkins, who has recently resigned the Professorship of Geology and Palæontology at the Manchester University, belongs to the comparatively rare, and now dwindling, group of naturalists who have extended their energies across the borderlands of their main subjects, and have become recognized as authorities also in neighbouring territories. If Boyd Dawkins had not been famous in the realm of Geology, he would still have been a prominent figure among anthropologists and archæologists; and if he had not established for himself a name among those whose researches have enriched the data and philosophy of science, he would still have been prominent as a teacher, an organizer, and a public-spirited citizen. Forty years ago, when there were two small collections of natural-history objects in Manchester, the late Professor Huxley nominated young Dawkins as the man with the requisite amount of energy, business capacity, and scientific knowledge to organize a central institution, which, now, under the control of the new University of Manchester, is an institution of importance as much to the student who requires reference materials as to the general public. Although the Manchester Museum has now attained dimensions requiring the superintendence by specialists in the three main branches of Natural History, the organization is the direct outcome of its first Curator, through whose influence mainly the money required for buildings has been obtained, and through whose attraction unique collections of materials have been secured.