Halstead Hospital

The Centenary Meeting of the Royal Medico-Psychological Association should have taken place in 1940. I was honoured in 1939 by the Association nominating me as President-Elect. Much has happened since then, and for five years we have met under the able presidency of Dr. T. C. Graves, whose inaugural meeting had necessarily to be a short one; it was held in London and was limited to the delivery of his presidential address. I feel that we owe a great debt to Dr. Graves for his constant attendance and work, often under difficult war conditions.

We present a complete phylogeny of macroperforate planktonic foraminifer species of the Cenozoic Era (∼65 million years ago to present). The phylogeny is developed from a large body of palaeontological work that details the evolutionary relationships and stratigraphic (time) distributions of species-level taxa identified from morphology ('morphospecies'). Morphospecies are assigned to morphogroups and ecogroups depending on test morphology and inferred habitat, respectively. Because gradual evolution is well documented in this clade, we have identified many instances of morphospecies intergrading over time, allowing us to eliminate 'pseudospeciation' and 'pseudoextinction' from the record and thereby permit the construction of a more natural phylogeny based on inferred biological lineages. Each cladogenetic event is determined as either budding or bifurcating depending on the pattern of morphological change at the time of branching. This lineage phylogeny provides palaeontologically calibrated ages for each divergence that are entirely independent of molecular data. The tree provides a model system for macroevolutionary studies in the fossil record addressing questions of speciation, extinction, and rates and patterns of evolution.

Abstract This paper is concerned with the axially symmetric plastic flow of a rigid-plastic nonhardening material which obeys the Tresca yield criterion of constant maximum shearing stress and the associated flow rule. A general discussion of the basic equations is given. The discussion shows that the hypothesis of Haar and von Kármán is likely to be of great importance in the solution of axially symmetric problems. This conclusion is substantiated by the remainder of the work which considers problems in which the hypothesis is satisfied, i.e. problems in which the circumferential stress is equal to one of the principal stresses in the meridional planes. Possible plastic velocity fields in a circular cylindrical bar stressed to yielding in compression or tension are obtained in §3. Section 4 examines plastic stress fields in the neighbourhood of stress-free conical surfaces. In the final sections of the paper, the plastic stress field and a permissible deformation mode for the problem of the indentation of the plane surface of a semi-infinite body by a circular flat-ended rigid punch are obtained. It is shown that the plastic stress field near the punch can be extended into the rigid region without violating the yield criterion.

This article provides a review of the published literature describing the use of biosensors and biologically-inspired systems for explosives detection. The review focusses on the use of antibodies, enzymes, biologically-inspired synthetic ligands and whole-cell biosensors, providing a flavour of the range of technology, formats and approaches that can be used to detect explosives using biological systems.

Abstract An original method of integration is described for quasi-linear hyperbolic equations in three independent variables. The solution is constructed by means of a step-by-step procedure, employing difference relations along four bicharacteristics and one time-like ordinary curve through each point. From these difference relations the derivatives of the dependent variables at the unknown point are eliminated. The solution at any point can then be com­puted, with an error proportional to the step size cubed, without referring to conditions outside its domain of dependence. The application of the method to the systems of equations governing unsteady plane motion and steady supersonic flow of an inviscid, non-conducting fluid is discussed in detail. As an example of the use of the method, the flow over a particular delta-shaped body has been computed.

Ninety patients with rheumatoid arthritis completed a double-blind crossover trial comparing fenoprofen, ibuprofen, ketoprofen, and naproxen. Fenoprofen and naproxen were slightly more effective than the other two drugs but there were striking individual variations in response. Groups of patients could be identified who preferred each of the four drugs. The commonest side effects were those related to the upper gastrointestinal tract; these showed individual variation and seldom occurred with more than one or two of the drugs. Side effects were least common with ibuprofen and naproxen. Since naproxen combined greater effectiveness with a lower incidence of side effects it must be regarded as the first choice among these drugs. It may be necessary to try several drugs before finding the right one for a particular patient.

The present volume is written from the author's large surgical and pathological experience with patients having disorders of the thyroid gland. Sections are devoted to the normal morphology of the thyroid gland and its general pathology. The various manifestations of thyroid gland disorders in childhood, non-toxic and toxic nodular goiters, and diffuse toxic goiter are treated in regard to pathogenesis, pathology, clinical manifestations, and treatment. In addition accounts of the inflammatory states of the thyroid gland, myxedema, thyroidal neoplasms, and aberrant goiters are given. A special chapter is devoted to the important relationship between toxic goiter and heart disease under the designation “cardiotoxic goiter.” The hospital management of goiter patients, including pre- and post-operative care, the complications of surgery, and the after-course of the patients are treated at length. Finally there are sections on surgical anatomy and the technique of operative procedures.

The detection and quantification of triacetone triperoxide (TATP) using LC/MS is investigated. GC/MS analysis of TATP is hindered by stationary phase activation in very short periods of time. Due to the lower temperatures used in LC. this problem is not encountered. This study presents a method that is suitable for the detection of TATP at levels as low as 100 pg microl(-1) (10 ng per 100 microl). Initial findings are also reported for the investigation of a secondary chromatographic peak, which is thought to be caused by separation of two conformers. This study concludes that LC/MS is a suitable technique for the analysis of trace levels of TATP.

Langstroth and Gillespie have determined experimentally the rate of change of particle number in ammonium chloride smokes in still and moving air, and have analysed their results into deposition on the walls and coagulation inside the aerosol cloud It is shown here that the empirical constants describing these processes can be explained on theoretical grounds, both in order of magnitude and as regards their variation with the rate of stirring

Abstract The principles behind the use of polymeric binders in composite propellants and explosives are described with emphasis on the properties which they should possess in order to satisfy the requirements for inclusion in a composition. The desirability of using energetic polymers as binders in terms of both performance and safety, and the problems associated with their preparation and properties, are discussed. The contributions of chemical synthesis within DRA to overcome these problems will be shown. Preparation of energetic polymers both by polymer modification and by polymerization of an energetic monomer is described. We have developed three energetic polymers: poly‐3‐nitratomethyl‐3‐methyloxetane (polyNIMMO), polyglycidyl nitrate (polyG‐LYN) and nitrated hydroxy‐terminated polybutadiene (NHTPB). Two of these (polyNIMMO and polyGLYN) have shown excellent properties in propellant and explosive formulations and proved that low‐vulnerability, high‐performance compositions are possible. The properties of the products from our work are compared with those of other groups and a glimpse of the future in this area is given to show the potential for new energetic polymers.

Abstract A computational analysis is performed of self-sustained oscillatory flow over a cavity driven by a shear layer at Mach 1·5. The unsteady flow is studied through solutions of the Reynolds-averaged Navier-Stokes equations with turbulence modelled by a two-equation k-ω model. The trailing edge (face) of a baseline rectangular cavity is modified using wedge and ramp shapes to investigate means for the suppression and attenuation of the self-sustained oscillation. Through modification of the shear layer impingement, both wedge and ramp are effective in reducing the level of oscillation. The time-averaged pressure (form) drag coefficient of the cavity is also reduced significantly. The main cause of the drag reduction is the elimination or reduction of the high pressure area near the downstream corner of the cavity due to the presence of a vortex. Two types of unsteady flow exist when a curved ramp is employed: ‘regular’ and ‘random’. The use of a h = 0·6D ramp generates a random type pressure fluctuation with lower rms pressure compared with the h = 0·2D and 0·4D ramps.

To use porous silicon as an optical interferometric biosensor, the pores must be sufficiently large to allow easy ingress of reagents and the layer must also display Fabry-Perot optical cavity modes. Here the detection antibody is rabbit IgG and the analyte is α-rabbit IgG conjugated to horseradish peroxidase (HRP). For this model system, the pores should be >50 nm in diameter. Such diameters have been obtained in 0.05 Ω cm n-type silicon using anodisation followed by chemical etching in ethanolic KOH and also by anodising 0.005 Ω cm p-type material. The latter also displays optical cavity modes. The silicon surface is oxidised in ozone, silanised using aminopropylmethoxysilanes with one, two or three methoxy groups, and cross linked to IgG using glutaraldehyde. High specific binding is found for mono-, di- and tri-methoxy silanes, but the lowest non-specific binding is found for silanisation with the tri-methoxy silane.

Differences between training and working contexts have the potential to be a major cause of deficits in performance of searching animals. Detection responses of individuals trained with high rates of target stimulus presentation tend to extinguish when moved to a new context where their rate of target encountering is low. This problem is acute with some contraband and people detection dogs where the rate of target encountering in the work context is significantly lower than during training. While the rate of extinction can be mitigated by planting known targets in the working contexts, this is often logistically difficult, dangerous, or impractical; an alternative solution would therefore be beneficial. Here, we explore the novel approach of adding non-contraband target stimuli to the training set and then presenting these innocuous targets periodically in the work context, thereby avoiding the logistic difficulties attached to the use of real contraband targets. Our rationale is that the search persistence caused by the innocuous targets could generalise to the real targets, thus increasing resistance to extinction in the latter. The potential problem with this approach is that dogs may learn to focus on the innocuous targets in the work context to the detriment of the real targets. In our experiments, 21 dogs were trained with three contraband (explosive) and one innocuous (non-explosive) odours. When they were transferred to a “work” context, they were separated into three groups, as follows: Group “0T” (zero target) were not exposed to any targets in the work environment; Group 1T (one target) were exposed to and rewarded on one innocuous target in the work environment; and Group 3T (three target) were exposed to and rewarded on three contraband targets in the work location. These regimens continued for six weeks during which time all dogs received two refresher training days away from their work location, where they were rewarded on all four target odours. Following this work phase, search and detection performance was tested in the work location for all stimuli. In the work phase, search vigilance in the 0T group dropped considerably compared with the 1T and 3T groups. Critically, when dogs were re-exposed to all four targets in the work location at the end of the work phase, detection rates were significantly reduced for the 0T group, but were maintained on all targets for the 1T and 3T group. Our results show that rewarding search persistence with innocuous stimuli is potentially a successful strategy to maintain detection-dog performance across a range of trained contraband odours.

Neutron diffraction measurements have been made on deuterated methyl alcohol at 20°C using incident wavelengths of 0·7 and 0·5 Å. The cross-section data at large Q-values have been analysed with a molecular form factor to determine the geometrical parameters defining the conformation of the molecules. The results are in good agreement with other measurements on the vapour phase with the exception of the OD distance which is increased. This effect may be explained by the influence of hydrogen bonding between neighbouring molecules and is similar to the behaviour in water. The intermolecular contribution has also been obtained and transformed to give a composite pair correlation function for each dataset. The oscillatory structure extends to 12 Å and provides suitable information for comparison with computer simulation.

The first comprehensive assessment of 34 solid phase extraction sorbents is presented for organic explosive residues in wastewater prior to analysis with liquid chromatography-high resolution accurate mass spectrometry (LC-HRMS). A total of 18 explosives were selected including nitramines, nitrate esters, nitroaromatics and organic peroxides. Three polymeric divinylbenzene-based sorbents were found to be most suitable and one co-polymerised with n-vinyl pyrrolidone offered satisfactory recoveries for 14 compounds in fortified wastewater (77–124%). Limits of detection in matrix ranged from 0.026–23 μg L−1 with R2 ≥ 0.98 for most compounds. The method was applied to eight 24-h composite wastewater samples from a London wastewater works and one compound, 2,4-dinitrotoluene, was determined over five days between 332 and 468 g day−1 (225–303 ng L−1). To further exploit the suspect screening capability, 17 additional explosives, precursors and transformation products were screened in spiked wastewater samples. Of these, 14 were detected with recoveries from 62 to 92%, highlighting the broad applicability of the method. To our knowledge, this represents the first screen of explosives-related compounds in wastewater from a major European city. This method also allows post-analysis detection of new or emerging compounds using full-scan HRMS datasets to potentially identify and locate illegal manufacture of explosives via wastewater analysis.

The detection and quantification of trace amounts of hexamethylenetriperoxidediamine (HMTD), a primary organic peroxide explosive, is investigated by LC/MS. LC/MS is well suited to the analysis of explosive compounds, such as HMTD, that are thermally labile. This property of HMTD has prevented other chromatography separation techniques, such as GC/MS, from being successfully employed for the analysis of HMTD. In this paper, the development of an LC/MS method capable of detecting trace quantities of HMTD is described. Potentially, the method is capable of being used to detect a lower detection limit of 20 pg µl−1 (2 ng per 100 µl) of HMTD. In comparison to other chromatography separation techniques that are used for analysis of explosives and explosive mixtures, e.g. GC/MS and GC/TEA, this represents an extremely valuable technique.

The ideal and actual characteristics of specialist search dogs have been examined in questionnaire surveys of 244 dog handlers and trainers from the six main UK dog-using Government agencies. The ten most important characteristics were (ideal level in brackets): acuity of sense of smell (very high), incentive to find an object which is out of sight (very high), health (very high), tendency to hunt by smell alone (very high), stamina (very high), ability to learn from being rewarded (very high), tendency to be distracted when searching (very low); agility (high), consistency of behaviour from day to day (high), motivation to chase an object (high). Significant differences between actual and ideal levels were found for 22 of the 30 characteristics, predominantly in undesirable attributes, suggesting that there is scope for significant improvement in operational effectiveness.

Many patients with cancer receive multiple chemotherapy agents as well as other medications for coexisting medical conditions. Despite the introduction of 5-HT3 receptor antagonists, the management of nausea and vomiting following cancer treatment and after cancer surgery remains complex, particularly when patients are receiving multiple prescription medications. As a drug class, the 5-HT3 receptor antagonists have good antiemetic efficacy and an improved safety profile over conventional antiemetics. Nevertheless, pharmacologic differences exist between these agents, such as their interaction with the metabolic cytochrome P450 system. This review examines the major metabolic differences between the most frequently prescribed 5-HT3 receptor antagonists, dolasetron, granisetron, ondansetron, and tropisetron. The potential drug interactions that these differences may precipitate and key genetic interindividual variations in drug metabolism are also considered. To avoid or minimize potential drug interactions, the 5-HT3 receptor antagonist with the lowest risk of these interactions should be considered as first choice.

The sensitivity of the optical reflectivity of porous silicon structures to the refractive index of liquid within the pores is studied for a single layer, a Bragg mirror and a microcavity. Sucrose solutions of concentration in the range 0.05 to 1.0% by weight are introduced into the pores within a flow cell in order to change the refractive index of the liquid in the pores from 1.3330 to 1.3344. Optimum wavelengths for detection via reflectivity changes are determined based on a signal to noise analysis. The optical thickness of the single layer is also monitored by measuring the fringe spacing via a Fourier transform technique. It is just possible to detect the effect of a change in refractive index of liquid in the pores of 0.00007 for both the reflectivity and optical thickness approaches.

An immunoperoxidase technique for the histological demonstration of Carcinoembryonic Antigen (CEA) was applied to paraffin sections from 74 breast carcinomas and 43 benign breast lesions. Sixty-six per cent of the carcinomas and the only case of granular cell myoblastoma examined were CEA positive. Two examples of mammary dysplasia (7%) showed foci of CEA positive acini. All tumour tissue found in lymphatics and in metastases in lymph nodes was CEA positive, including two cases where the primary tumour was CEA negative, and all the metastases examined from CEA positive tumours. A significant relationship was found between CEA positivity of the primary tumour and the presence of lymph node metastases.