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Pore-forming peptides are of interest due to their antimicrobial activity and ability to form gateways through lipid membranes. Chemical modification of these peptides makes it possible to arrange several peptide monomers into well-defined pore-forming structures using various templating strategies. These templated super-structures can exert antimicrobial activity at significantly lower total peptide concentration than their untemplated equivalents. In addition, the chemical moieties used for templating may be functionalized to interact specifically with targeted membranes such as those of pathogens or cancer cells. A range of molecular templates has been explored, including dimerization of pore-forming monomers, their covalent attachment to cyclodextrin, porphyrin or fullerene scaffolds as well as attachment of amino acid linkers or nucleic acid constructs to generate assemblies of 4 to 26 peptides or proteins. Compared to free peptide monomers, templated pore assemblies showed increased membrane affinity, prolonged open-state lifetimes of the pores and more frequent pore formation due to higher local concentration. These constructs are useful model systems for biophysical studies to understand porin and ion channel proteins and their mechanisms of insertion into lipid membranes. Recently designed DNA-templates are expanding the usefulness of templated pore assemblies beyond applications of cell killing and may include targeted drug delivery and accelerate the emerging field of single-molecule detection and characterization of biomolecules by nanopore-based resistive pulse sensing.

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The development of new materials with reduced noise and vibration levels is an active area of research due to concerns in various aspects of environmental noise pollution and its effects on health. Excessive vibrations also reduce the service live of the structures and limit the fields of their utilization. In oscillations, the viscoelastic moduli of a material are complex and it is their loss part - the product of the stiffness part and loss tangent - that is commonly viewed as a figure of merit in noise and vibration damping applications. The stiffness modulus and loss tangent are usually mutually exclusive properties so it is a technological challenge to develop materials that simultaneously combine high stiffness and high loss. Here we achieve this rare balance of properties by filling a solid polymer matrix with rigid inorganic spheres coated by a sub-micron layer of a viscoelastic material with a high level of internal friction. We demonstrate that this combination can be experimentally realised and that the analytically predicted behaviour is closely reproduced, thereby escaping the often termed 'Ashby' limit for mechanical stiffness/damping trade-off and offering a new route for manufacturing advanced composite structures with markedly reduced noise and vibration levels.

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Classifying a set of objects into clusters can be done in numerous ways, producing different results. They can be visually compared using contingency tables, mosaicplots, fluctuation diagrams, tableplots, (modified) parallel coordinates plots, Parallel Sets plots or circos diagrams. Unfortunately the interpretability of all these graphical displays decreases rapidly with the numbers of categories and clusterings. In his famous book A Semiology of Graphics Bertin writes "the discovery of an ordered concept appears as the ultimate point in logical simplification since it permits reducing to a single instant the assimilation of series which previously required many instants of study". Or in more everyday language, if you use good orderings you can see results immediately that with other orderings might take a lot of effort. This is also related to the idea of effect ordering, that data should be organised to reflect the effect you want to observe. This paper presents an efficient algorithm based on Bertin's idea and concepts related to Kendall's t, which finds informative joint orders for two or more nominal classification variables. We also show how these orderings improve the various displays and how groups of corresponding categories can be detected using a top-down partitioning algorithm. Different clusterings based on data on the environmental performance of cars sold in Germany are used for illustration. All presented methods are available in the R package extracat which is used to compute the optimized orderings for the example dataset.

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Although many PCL injuries are in combination with posterolateral corner (PLC) injuries, there has been little work done on combined injury reconstruction; the literature includes differing recommendations. It was hypothesised that a double-bundle PCL reconstruction would restore both posterior drawer and external rotation laxities closer to normal than an isolated single-bundle reconstruction in combined PCL plus PLC-deficient knees. However, it was also hypothesised that an isolated PCL reconstruction would still leave abnormal rotation laxity. In this controlled laboratory study, cadaver knee kinematics were measured electromagnetically with posterior drawer, external rotation, varus rotation loads applied, at sequential stages: intact; PCL-deficient; PCL plus PLC-deficient; double-bundle PCL reconstruction; single-bundle PCL reconstruction. The grafts were tensed using a posterior drawer laxity matching protocol. There was no significant difference between single- and double-bundle PCL reconstructions at any angle of flexion: both reconstructions restored posterior drawer to normal; neither reconstruction restored external rotation or varus laxity to normal. We concluded that, in combined PCL plus PLC deficiency, isolated PCL reconstruction only controls tibial posterior drawer, but is not sufficient to restore rotational laxity to normal. Double-bundle PCL reconstruction was not better than single-bundle, so the added complexity of double-bundle reconstruction does not seem to be justified by these results.

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Proponents of hamstring anterior cruciate ligament (ACL) reconstruction suggest that anterior knee symptoms (AKS) may be less than following the use of bone-patella-bone autograft. Our aim was to assess the incidence of AKS in a cohort of patients who had undergone hamstring reconstructions. Forty-four of 50 consecutive patients who had undergone arthroscopically assisted four-strand gracilis/semitendinosus hamstring ACL reconstructions were reviewed at a minimum follow-up of 24 months. The frequency and severity of anterior knee pain experienced during activities of daily living, sports, prolonged sitting, stair-climbing and kneeling was recorded by means of the Shelboume and Trumper anterior knee pain questionnaire. The location of both pain and any perceived sensory change was recorded using patient-drawn diagrams. Although mild or moderate symptoms occurred in a proportion of patients, only 2% experienced significant symptoms that caused limitation with daily activity, 7% with strenuous work or sport, 12% with kneeling, 5% with stairs and none with prolonged sitting. The pain was not specifically related to the incision for tendon harvest and drilling of the tibial tunnel. Areas of sensory change over the front of the knee were identifiable in 50% of patients, and of these, 86% demonstrated sensory change in the distribution of the infragenicular branch of the saphenous nerve. Although rarely a cause of limitation of activity, AKS can be a problem after hamstring ACL reconstruction and patients should be counselled accordingly.

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We have reviewed 33 patients undergoing primary reconstruction of the anterior cruciate ligament with a four-strand hamstring graft to assess the analgesic effect of a '3 in 1' lumbar plexus block. Patients were randomised into two groups to determine whether or not they received a catheter infusion of bupivacaine for 24 h after operation. Pain scores and additional analgesic requirements were assessed at 4, 8, 12, 16, 20 and 24 h after surgery. No difference was found between the two groups in terms of pain scores (P=0.884) and the numbers requiring morphine were similar (5/16 and 7/17). There was a trend (2.0 vs. 3.4 tablets) towards a greater coproxamol requirement for the non-block group, although not quite statistically significant (P=0.06). We conclude that the additional risk and cost of '3 in 1' lumbar plexus blockade is not justifiable after this procedure.

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We obtained samples of spinal accessory nerve from patients undergoing radical surgery for tumours or nerve grafting in the neck. These were analysed by light and electron microscopy for the type of fibre. All contained fibres consistent with non-proprioceptive sensory function including pain.

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We surveyed all surgically qualified members of the British Orthopaedic Association as to their views on thromboprophylaxis in routine total hip and knee replacement. The response rate was 92%. In total hip replacement, 13-15% of surgeons used no method of prophylaxis at all, 18-22% did not use a mechanical method of prophylaxis, while 26% did not use a pharamacological agent; 36% believed low-dose anticoagulant thromboprophylaxis to be a medicolegal necessity while 47% disagreed with this. In total knee replacement, 18-33% of surgeons used no method of prophylaxis at all, 20-26% did not use a mechanical method of prophylaxis, while 54-58% did not use a pharmacological agent; 12 believed low-dose anticoagulant thromboprophylaxis to be a medicolegal necessity, while 64% disagreed with this. We conclude that mechanical methods remain a popular method of thromboprophylaxis and pharmacological methods, while commonly used, are not seen as a medicolegal requirement in lower limb arthroplasty and are used less often in total knee replacement.

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We present a method allowing intra-operative monitoring of the common peroneal nerve during total knee arthroplasty using a magnetic stimulator. Previous reports have shown no pre-operative method successful in selecting those patients prone to develop a post-operative palsy. The device, placed beneath the lumbar spine, stimulates the cauda equina; common peroneal nerve function is assessed via the response in extensor digitorum brevis. There is a loss of signal from the nerve with the use of a tourniquet 25 min following its application. The protocol therefore requires that a tourniquet is used at least only for fixation of the prosthetic components. The method is quick, safe, non-invasive and reproducible, and is of use both in at-risk patients and in research work.

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We compared the 3-month dislocation rate for hip hemiarthroplasties inserted via the posterior and direct lateral routes. In all, 2906 primary hemiarthroplasties, performed between 1986 and 1992 in four hospitals on a training hospital rotation, were analysed. The posterior approach was used in 1656 (57%) and the lateral in 1250 (43%). The groups were otherwise comparable. The overall dislocation rate for the posterior approach was 9.0% (149/1656), whereas that for the direct lateral approach was 3.3% (41/2150). The difference is statistically highly significant. In addition, we analysed the dislocation rate for each approach in the three broad groups of surgical trainee. For senior registrars, there was no statistical difference in the dislocation rate. However, for registrars and senior house officers, there were statistically highly significant differences in the dislocation rate for posterior and direct lateral approaches (8.4% vs 3.3% and 14.2% vs 3.6%, respectively). We conclude that, because of the high mortality associated with dislocation of a hemiarthroplasty, the posterior approach for this operation should now be abandoned, especially by surgical trainees early in their careers.

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OBJECTIVE: To compare the classic clomiphene citrate (CC) and hMG regime for ovarian stimulation before IVF in women who received hMG post-long protocol down-regulation with either 3 mg triptorelin [INN] IM or 150 mg buserelin acetate four times daily intranasally. Furthermore, if possible, to determine the preferred method of down-regulation. DESIGN: A prospective study of 150 women randomized blind to the clinician to one of three alternative ovarian stimulation regimes when passing for the first time through an IVF program during 1992. RESULTS: Triptorelin [INN] down-regulated significantly more quickly than buserelin acetate. The non-down-regulated group CC and hMG used significantly less hMG in a shorter time. In these women LH levels at hCG administration were significantly higher. No other intergroup differences were found. Pregnancy and take-home baby rates for the overall study were, respectively, 32%:25% (per cycle) and 42%:33%; (per ET) for the triptorelin [INN] group 28%:22% and 39%:31%; the CC group 32%:24% and 46%:34%; and the buserelin acetate group 34%:28% and 42%:34%. CONCLUSIONS: Triptorelin [INN] and buserelin acetate were comparable in all parameters except down-regulation. The former was significantly quicker and more sure. In none of the clinical end points measured, however, was the classic CC and hMG non-down-regulation regime significantly less effective or troublesome than where down-regulation was used. These results therefore show that although indications for down-regulation before IVF exist, it should not be used on all patients.

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Shot blasted titanium alloy femoral components with a coarse finish were withdrawn from use in 1987 following reports of early component failure. We reviewed all coarse titanium femoral stems used in primary total hip arthroplasty in our institution between 1985 and 1987 and compared them to a similar stem made of vitallium which was also used over the same period. We found that, at an average of 5.2 years following implantation, over two-thirds of titanium components were associated with endosteal lysis. In many of the cases the early lytic changes were asymptomatic with significant bone loss occurring prior to presentation. We discuss our findings in relation to revision surgery. We advocate that all those with coarse stem titanium components should be positively reviewed to detect early lytic change before extensive bone destruction occurs.

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There were 28,600 deliveries of 500 g or more to women at the Rotunda Hospital between January 1st 1985 and December 1st 1989. Of these, 595 were to women aged 40 years and over. Thirty-five variables of clinical significance were analyzed, comparing those of 40 years of age and more with those under 40. The older group had significant increases in gestational diabetes, ante-partum hemorrhage, fetal distress, prematurity, low birth weight and perinatal mortality. Chromosome congenital abnormalities were significantly higher, particularly Down syndrome. There were significantly increased rates of induction and cesarean section in the older women. Some evidence of interaction of age with other factors was found, however these were difficult to separate out in the clinical setting. We therefore recommend it wiser to manage all elderly gravidas in a high risk manner dealing with cases individually within this framework. Intervention should, however, need to be justified in the older as in the younger woman.

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