Modal testing for model validation of structures with discrete nonlinearities.

Model validation using data from modal tests is now widely practiced in many industries for advanced structural dynamic design analysis, especially where structural integrity is a primary requirement. These industries tend to demand highly efficient designs for their critical structures which, as a result, are increasingly operating in regimes where traditional linearity assumptions are no longer adequate. In particular, many modern structures are found to contain localized areas, often around joints or boundaries, where the actual mechanical behaviour is far from linear. Such structures need to have appropriate representation of these nonlinear features incorporated into the otherwise largely linear models that are used for design and operation. This paper proposes an approach to this task which is an extension of existing linear techniques, especially in the testing phase, involving only just as much nonlinear analysis as is necessary to construct a model which is good enough, or 'valid': i.e. capable of predicting the nonlinear response behaviour of the structure under all in-service operating and test conditions with a prescribed accuracy. A short-list of methods described in the recent literature categorized using our framework is given, which identifies those areas in which further development is most urgently required.

Effect of a pathway bundle on length of stay.

BACKGROUND: Pathways to guide clinical care are well accepted and used in many emergency departments. We wanted to introduce a number ("bundle") over a short space of time and involve the whole patient stay in the pathway. It was hypothesised that a more efficient process would result with an overall reduction in length of stay (LoS). METHODS: A "bundle" of 14 evidence-based pathways of care was introduced into a medium-sized district general hospital (DGH) in late 2006/early 2007. These pathways covered emergency department care and acute medical care for a period of up to 48 h. A total of 8184 acute emergency admission episodes were audited, 3852 in the 8 months before introduction of the new pathways and 4332 in the 8 months after their introduction. RESULTS: The overall effect of introducing the pathway bundle had a trend towards reduction in LoS by 0.2 days (95% CI -0.2 to 0.5), but this was not statistically significant (p>0.1). However, in those patients with

Pregnancy and autoimmune thyroid disease.

Immunological and endocrine changes related to pregnancy influence the course and development of autoimmune thyroid disease (AITD). Conversely, the presence of AITD can affect both the mother and her child-both in utero and in the neonatal period. The successful management of AITD in pregnancy requires a knowledge of the differential placental transfer of various hormones, antibodies, and drugs.

Mapping epitope specificities of monoclonal antibodies to thyroid peroxidase using recombinant antigen preparations.

Five separate monoclonal antibodies (MoAbs) to human thyroid peroxidase (hTPO) were raised by immunising Balb/c mice with hTPO purified from detergent solubilised thyroid microsomes by high performance liquid chromatography (HPLC). The epitope specificities of these MoAbs were determined by assessing their ability to bind to purified recombinant fusion protein fragments of human TPO (TPO(r)) generated in E. coli. A total of seven small overlapping fragments (averaging 104 amino acid residues) of hTPO, encompassing over 90% of the extracellular region of the molecule, were generated as glutathione S-transferase (GST) fusion proteins. The sequential epitopes on TPO(r) recognised by these MoAbs were analysed by both immunoblotting and enzyme linked immunosorbent assay (ELISA). Two different MoAbs (A4 and A5) recognised sequential epitopes within the TPO(r) preparation termed R1a + b (residues 1-160) and more specifically, in the case of MoAb A4, within the subfragment R1b (residues 70-160). The inability of the other MoAbs (A1-A3) to recognise recombinant fragments, suggests they either recognise conformational determinants on the TPO molecule or epitopes that are present on the small regions of the TPO molecule which have not been expressed as recombinant proteins.

Mapping of autoantigenic epitopes on recombinant thyroid peroxidase fragments using the polymerase chain reaction.

Cloned cDNA templates of thyroid peroxidase (TPO) have been used in conjunction with the polymerase chain reaction (PCR) to express selected segments of the thyroid microsomal/peroxidase antigen (TMA/TPO) as recombinant protein in E. coli. Six small, different recombinant fragments averaging 120 amino acid residues and one large fragment (269 amino acids) of TPO which together encompass 80% of the extracellular region of the molecule have been produced and autoantibody (aAb) binding sites analysed by immunoblotting. A minimum of six independent, sequential antigenic determinants have been localized on the recombinant proteins and these map to the amino terminal, the central core region and the carboxyl terminal of the TPO molecule. More accurately, the six antigenic sites reside on overlapping recombinant TPO preparations termed R1a + R1b (residues 1 to 160) R1c (residues 145 to 250), R2b (residues 457 to 589), R3a (residues 577-677), R3b (residues 657-767) and R3c (residues 737-845). The large fragment of TPO termed R3 (residues 577-845) encompassing R3a, R3b and R3c also reacts with the aAbs. Different sera from patients with autoimmune thyroid disease contain antibodies to TMA/TPO which differ in their fine specificity. The use of recombinant molecular biological techniques together with PCR to prepare small segments of a large autoantigen as recombinant protein will now allow studies to progress on autoepitope mapping of the precise amino acid sequences of the TPO molecule with the use of synthetic peptides.

Instrumentation to evaluate neural signal recording properties of micromachined microelectrodes inserted in invertebrate nerve.

The design and characterization of instrumentation for application in evaluating the neural signal recording properties of probe-type microelectrodes, micromachined from silicon, are reported. Key aspects include the close matching of gain and frequency response between channels (better than 1%), flexibility in signal conditioning options, the ability to operate with a wide range of (microelectrode) recording site dimensions (4 microm x 4 micrm to 50 microm x 50 microm), and hence impedances, and the facility to monitor and store instrumentation settings on computer along with the recorded signals. Noise levels ranged from 3.7 microV rms for a 50 microm site, to 11.7 microV rms for a microm site, measured in saline. Close matching between channels was required to enable comparisons between different sites and different probes to be made with confidence; however, the instrumentation could be readily applied to less demanding applications.

Comparative analysis of power-line interference between two- or three-electrode biopotential amplifiers.

Differential input amplifiers are commonly used in the measurement of biopotential signals. This is because of their ability to reject common-mode signals, for example power-line interference. Rejection is further enhanced by referencing the subject to the instrumentation system. One such referencing technique uses a third subject electrode connected either to circuit common or to ground. However, these techniques are rarely explained or quantified in the literature. Four recording configurations are examined, isolated and non-isolated amplifiers with two and with three electrodes, and existing models are extended. From a brief assessment of power-line interference sources, it is concluded that only displacement currents induced into the leads and the body need be considered. The effect of these on the four configurations is analysed using SPICE. Results show that interference from displacement currents induced into the leads and into the body is dependent upon the recording configuration used and is significantly lower in three-electrode than in two-electrode amplifiers. Isolation also reduces levels of interference. It is concluded that the choice of referencing may affect interference levels on the biopotential signal significantly. Experimental and further analytical work is planned to confirm this.

Silicon-based microelectrodes for neurophysiology, micromachined from silicon-on-insulator wafers.

A process is described for the fabrication of silicon-based microelectrodes for neurophysiology using bonded and etched-back silicon-on-insulator (BESOI) wafers. The probe shapes are defined without high levels of boron doping in the silicon; this is considered as a step towards producing probes with active electronics integrated directly beneath the electrodes. Gold electrodes, of 4 microns by 4 microns to 50 microns by 50 microns are fabricated on shanks (cantilever beams) 6 microns thick and which taper to an area approximately 100 microns wide and 200 microns long, which are inserted into the tissue under investigation. The passive probes fabricated have been successfully employed to make acute recordings from locust peripheral nerve.

The development of a long, dual-platform triaxial walkway for the measurement of forces and temporal-spatial data in the clinical assessment of gait.

Force-plate measurement of the ground reaction force (GRF) has, for many years, been considered a vital component of the comprehensive assessment of human gait in the clinical context. For example, the data can be used in the adjustment of prostheses and orthoses and in identifying the mechanisms underlying a gait dysfunction. However, commercial force plates are usually only capable of measuring GRF data from one step in a single traverse. That can lead to problems of 'targeting' and, with less able subjects, fatigue before the necessary data have been collected. Previous work at the University of Surrey resulted in a prototype dual-platform force walkway capable of measuring the vertical component of the GRF and estimating the position of application of that force for multiple foot contacts in a single traverse. In addition, temporal-spatial information, e.g. speed and step length, could also be determined. This paper describes the development of a longer walkway that can measure the three orthogonal components of the GRF and provide and a more accurate estimate of the position of application of that force. Software to allow the rapid reduction of gait data to useful clinical information has also been developed.

Computerised updating of clinical summaries: new opportunities for clinical practice and research?

A new type of clinical summary, produced by copying standard descriptions of diseases on to a computer screen and editing them to match a patient's findings and diagnoses, was updated and reprinted as the patient's condition changed in the ward or as an outpatient. When this method was used to produce typed medical discharge summaries over a three month period, 73 out of 91 (80%) were sent out within a week after discharge compared with five out of 56 (9%) conventionally typed summaries received in a single general practice. Even completely new computerised summaries are quicker for the secretary to produce than conventional summaries, and the computerised summaries are designed to be scanned rapidly for relevant information. They can also be used to collect data automatically for research, clinical audit, and resource management.

The incidence and occupational outcome of overuse anterior knee pain during army recruit training.

OBJECTIVES: To determine the incidence and occupational outcome of overuse anterior knee pain (AKP) in Army recruits undergoing basic training. METHODS: A prospective cohort study of 1008 Army recruits. Recruits underwent the 12-week phase 1 training program. Cases of AKP were captured through self-presentation of pain at a primary care medical centre. All recruits medical records were reviewed on leaving training and any other lower limb injuries were recorded for comparison with the AKP group. Training outcomes in terms of medical discharges (MD) and discharges as of right (DAOR) i.e, voluntary discharge, were recorded along with training days lost (TDL) and whether a recruit had been held back in training (BS). RESULTS: 8.75% (95% CI: 6.93-10.57) of recruits reported to the medical centre with AKP. Of these more than half were referred to see a GP and the majority were from patients with no previous history of AKP (91%, 95% CI: 85.2-97.5). The median TDL per AKP case was 3 days (IQR: 3-5 days). The AKP group had a significantly higher (p < 0.01) MD rate (12.5%) than the lower limb injury group (3.3%; 95% CI diff: 1.1-17.2%) and the baseline rate of all other recruits (2.5%; 95% CI diff: 2.3-17.7%). The majority of AKP cases occurred by week 4 (median) of training (IQR: 2.2-64). CONCLUSIONS: There was a high incidence of AKP, and while the short term prognosis appears relatively good in the majority of cases as reflected in the median TDL, a large minority were medically discharged and held back in training. Further work should examine methods of reducing the disease burden of AKP in the Army, addressing areas such as aetiology, prevention and treatment.

Motor asymmetry and estimation of body-scaled aperture width in Parkinson's disease.

The present study examined how asymmetrical motor symptomatology helps predict the pattern of perceptual judgements of body-scaled aperture width in lateralised Parkinson's disease (PD). Eleven patients with PD predominantly affecting the left side of their body (LPD), 16 patients with PD predominantly affecting their right side (RPD), and 16 healthy controls made forced-choice judgements about whether or not they would fit without turning their shoulders through a life-sized schematic doorway shown on a large screen. Whereas control and LPD groups made accurate estimations of body-scaled aperture width, RPD patients significantly underestimated aperture width relative to their body, perceiving doorways on average that were 12% narrower than their bodies as wide enough to allow them to pass through without rotation. Across all patients, estimates of body-scaled aperture width correlated with ratio of right-to-left symptom severity. These perceptual errors may indicate a mismatch between the neural representation of external space and that of body size in PD.

Natural frequency analysis of osseointegration for trans-femoral implant.

Osseointegration trans-femoral implants are a new orthopaedic anchoring method to attach prosthetic limbs. The clinical success of this promising technique depends on the effectiveness of osseointegration achieved after implantation. The aim of this study is to use the resonant characteristics of the implant system to determine the changes in stability as a reflection of boundary condition of the implant. With a small mechanical excitation, Vibration responses of the trans-femoral implant to a small mechanical excitation were measured using an accelerometer and the vibration signal was analyzed using Fast Fourier Transform (FFT) software to obtain the fundamental natural frequency (NF) of the implant system. In-vitro study was conducted using different silicone rubbers to simulate the interface condition. The result showed that a high NF corresponded to a high elastic modulus of the interface material between the implant and bone. A preliminary in-vivo study with one osseointegration trans-femoral implant patient showed that there was a decrease of NF after initial weight bearing rehabilitation. After continued weight bearing, the NF gradually returned to the pre-loading level at around day 24 and the general trend of the NF reached a stable state 38 days after the first weight bearing exercise.

A clinical comparison of the enzyme-linked immunosorbent assay (ELISA) and haemagglutination (TRC) in the routine detection of antithyroglobulin antibodies.

The enzyme-linked immunosorbent assay (ELISA) has been proposed as an alternative to haemagglutination (TRC) in the routine examination of sera for autoantibodies such as thyroglobulin antibody (Anti-Tg). However, very few clinical comparisons of the two tests, incorporating matched controls and an independent standard, have so far been published. We have compared the performance of ELISA and TRC as screening procedures in 814 patients referred to our autoimmune profile laboratory with clinically suspected thyrotoxicosis, Hashimoto's thyroiditis or myxoedema. Radioimmunoassay (RIA) was used as the independent standard, and the normal range for each test was established from 100 carefully age and sex-matched controls. Sixty-five % of the sera were negative in all three tests. The results from ELISA and RIA were very similar (r = 0.88, P less than 0.001), with no major discrepancy. TRC, however, was negative in 101 (40.2%) of 251 RIA positive sera (r = 0.61, P less than 0.001) and in 118 (44.2%) or 267 ELISA positive patients (r = 0.69, P less than 0.001). Some of the TRC negative sera were strongly RIA and ELISA positive. ELISA is fully quantitative, cheap, and was found to be more accurate than TRC in identifying anti-Tg positive individuals. It has the potential to replace TRC in the routine screening of sera for anti-Tg antibodies.

Long pulse biphasic electrical stimulation of denervated muscle.

In recent years a number of studies have employed long pulse biphasic stimulation as a treatment for denervated muscle to improve tissue quality and in some cases to improve contractile capability sufficient to restore function. However, in the U.K., this treatment is yet to be widely adopted clinically. A 5 subject, case based pilot study of long pulse biphasic direct stimulation of peripheral limb denervated muscle is being conducted and its effect on the tissue evaluated by measurement of muscle bulk, limb blood flow, and skin temperature. In cases of partial denervation. trapezoidal shaped pulses are used to minimize sensory and motor nerve fiber recruitment.