I22: SAXS/WAXS beamline at Diamond Light Source - an overview of 10 years operation.

Beamline I22 at Diamond Light Source is dedicated to the study of soft-matter systems from both biological and materials science. The beamline can operate in the range 3.7 keV to 22 keV for transmission SAXS and 14 keV to 20 keV for microfocus SAXS with beam sizes of 240 µm × 60 µm [full width half-maximum (FWHM) horizontal (H) × vertical (V)] at the sample for the main beamline, and approximately 10 µm × 10 µm for the dedicated microfocusing platform. There is a versatile sample platform for accommodating a range of facilities and user-developed sample environments. The high brilliance of the insertion device source on I22 allows structural investigation of materials under extreme environments (for example, fluid flow at high pressures and temperatures). I22 provides reliable access to millisecond data acquisition timescales, essential to understanding kinetic processes such as protein folding or structural evolution in polymers and colloids.

A facility for the analysis of the electronic structures of solids and their surfaces by synchrotron radiation photoelectron spectroscopy.

A synchrotron radiation beamline in the photon energy range of 18-240 eV and an electron spectroscopy end station have been constructed at the 3 GeV Diamond Light Source storage ring. The instrument features a variable polarisation undulator, a high resolution monochromator, a re-focussing system to form a beam spot of 50 × 50 µm2, and an end station for angle-resolved photoelectron spectroscopy (ARPES) including a 6-degrees-of-freedom cryogenic sample manipulator. The beamline design and its performance allow for a highly productive and precise use of the ARPES technique at an energy resolution of 10-15 meV for fast k-space mapping studies with a photon flux up to 2 ⋅ 1013 ph/s and well below 3 meV for high resolution spectra.

Antibiotic use is associated with resistance of environmental organisms in a teaching hospital.

An intensive care unit (ICU), acute stroke unit (ASU) and medical day bed unit (MDBU) underwent a standardized four-month environmental screening programme. The aim was to examine environmental organisms from these wards and compare bacterial resistances in association with antimicrobial usage. Hand-touch and other sites were screened using commercial dip-slides, and staff were asked to provide fingertip cultures. Patient blood isolates were retained throughout the study. Organisms were quantitatively and qualitatively assessed including antimicrobial susceptibility testing. Antibiotic consumption data in defined daily doses/1000 patient-days were obtained for each unit for the previous year. Two hundred and seventy-six staphylococci and 67 Gram-negative bacilli were recovered. Antibiotic resistance was significantly associated with individual wards for staphylococci (P<0.0001) and coliforms (P=0.04), and trends were also demonstrated for other Gram-negative organisms (P=0.06) despite fewer numbers. Antibiotic consumption on the ICU was six-fold higher than on the ASU and MDBU. Associations were found between consumption of selected antibiotic groups and corresponding resistances among staphylococci and Gram-negative bacilli. Antibacterial resistance was the only significant difference between environmental bacteria from different wards, and appeared to reflect prescribing pressure. Visual inspection of a ward may not provide a reliable guide regarding the presence of multi-resistant organisms in the hospital environment or the potential risk of infection. These findings have implications for local antibiotic policies, infection control and cleaning schedules.

Development of a multi-lane X-ray mirror providing variable beam sizes.

Grazing incidence mirrors are used on most X-ray synchrotron beamlines to focus, collimate or suppress harmonics. Increasingly beamline users are demanding variable beam shapes and sizes at the sample position. We have now developed a new concept to rapidly vary the beam size and shape of a focused X-ray beam. The surface of an elliptically figured mirror is divided into a number of laterally separated lanes, each of which is given an additional longitudinal height profile calculated to shape the X-ray beam to a top-hat profile in the focal plane. We have now fabricated two prototype mirrors and present the results of metrology tests and measurements made with one of the mirrors focusing the X-rays on a synchrotron beamline. We envisage that such mirrors could be widely applied to rapid beam-size switching on many synchrotron beamlines.

Molecular imprinting: at the edge of the third millennium.

Molecularly imprinted polymers (MIPs) represent a new class of materials that have artificially created receptor structures (1-3). Since their discovery in 1972, MIPs have attracted considerable interest from scientists and engineers involved with the development of chromatographic adsorbents, membranes, sensors and enzyme and receptor mimics.

Sputum and pulmonary function in asthma.

STUDY OBJECTIVE: To assess the relevance of sputum production to pulmonary function, in particular, persistent obstruction in patients with a primary clinical diagnosis of asthma. DESIGN: Cross-sectional study of all patients currently followed up in secondary care in a defined locality. SETTING: National Health Service and private clinics in north-east England. PATIENTS: All attenders, aged 18 years or older, with asthma, confirmed by reversibility of peak expiratory flow (PEF) by > or =15% and to > or =200 L/min. INTERVENTIONS: Pro forma history. Pulmonary function at attendance. Assessment of best function according to protocol. Measurement of actual FEV1, FVC, and PEF at attendance. MEASUREMENTS AND RESULTS: We studied 772 subjects; 387 (50%) were male; mean age was 55 years; atopic, 51%; current smokers, 11.5%; ex-smokers, 36%; and never smokers, 52.5%. Best pulmonary function was lower in chronic sputum producers (PEF, 83.2 vs 95.8; FVC, 67.9 vs 81.7% predicted). Chronic sputum production and its negative relationship with best function was strongly associated with smoking. There was little relationship between chronic sputum and persistent obstruction in nonsmokers. There were no univariate associations between sputum during attacks, or its color, and pulmonary function, but after allowing for demographic factors, including smoking, green sputum was associated with persistent obstruction. There was little relationship between sputum and actual/best function at attendance. CONCLUSIONS: Chronic sputum production is associated with persistent obstruction principally in those who have smoked, suggesting that the association reflects smoking rather than asthma. There is no interaction with atopy. After allowance for cigarette smoking, there is an association between green sputum production during exacerbations and persistent obstruction. Green sputum during relapse in asthma may indicate inflammation that is relevant to prognosis.

Clinicians' requirements for chemical sensors for in vivo monitoring: a multinational survey.

We report on a survey of senior clinicians in 11 countries which asked about what they see as the main areas where in vivo chemical sensors will be most useful in medicine, and about what their operating characteristics should be. This information may help those designing such sensors to match available and new technologies to clinical needs.

The design and development of new chemical sensors for in vivo monitoring.

The latest workshop of the European Community (EC) Concerted Action on 'Chemical sensors for in vivo monitoring' was held in Nauplion, Greece, in April this year. This fifth workshop focused on 'The design and development of new sensors for in vivo monitoring', and was organized into five sessions: design and development of new sensors; operational considerations; performance of analytical systems; novel sensors/tissue heterogeneity; and infra-red spectroscopy.

Monitoring freshwater sediments.

The objectives of the SENSPOL Expert Meeting on 'Monitoring Freshwater Sediments' held in Antwerp, Belgium, 12-13 September, 2001, were firstly to identify and define problems and secondly to develop a realistic strategy to solve these problems. Both of the stakeholder groups (governmental authorities and the dredging industry) present at the workshop participated in detailed discussions to elucidate the role of sensors in the field of sediments and sediment/water interfaces. The 19 invited experts were agreed that in situ monitoring systems are needed to monitor freshwater sediments. New recognised tools for sediment monitoring would help industry to meet the governmental sediment quality criteria and to handle the data concerning historic river contamination and geological background data. The need to monitor by effect-related studies together with chemical monitoring was stressed. The main focus for development of new sensor tools should be for on site determination of certain priority pollutants where there would be advantage over existing methods or where no suitable method exists, and to monitor biological effects (alarm systems and effect-related on site tests). Sensing technologies would also be useful to monitor bioavailability in sediments in situ to provide information for risk assessment. In addition, they could be of use to monitor bioremediation in situ. A useful role was forseen in dredging sediments, for in situ sediment screening and to guide treatment of dredged material. The new sensing tools presented, included determination of metal concentrations in sediments using the diffuse gradients in thin films (DGT) technique (Lancaster University, UK), an analytical protocol for determination of metal speciation in sediments (Universitat Autonoma de Barcelona, Spain), microbiotests for determination of sediment toxicity (University of Ghent, Belgium), a portable whole cell sensors device for heavy metal bioavailability (VITO, Belgium) and a microfabricated sensor array system for Pb concentration profile measurement in the microM range at the liquid-solid interface (University of Geneva, Switzerland).

Atropine acts in the ventral striatum to reduce raclopride-induced catalepsy.

While muscarinic receptor antagonists are used to reduce motor side effects associated with the use of antipsychotic drugs, their site of action remains unclear. The study investigated the site of action of the non-selective muscarinic receptor antagonist atropine on catalepsy induced by the selective dopamine D2 receptor antagonist, raclopride. Initially, catalepsy and striatal muscarinic receptor occupancy was assessed 2 h following subcutaneous injection of raclopride and either atropine or vehicle. Catalepsy was significantly reduced by doses of atropine that occupied more than 69% of muscarinic receptors. Next, atropine was injected bilaterally into the ventral striatum, which produced a significant reduction in catalepsy, while injections into the dorsal striatum and substantia nigra had no effect. The site of atropine's action was localised to a discrete area of the ventral striatum through the use of quantitative autoradiographic techniques. These findings provide further evidence for the importance of the ventral striatum in the expression of behaviours.

The Darlington and Northallerton Prospective Asthma Study: best function predicts mortality during the first 10 years.

The Darlington/Northallerton prospective study of asthmatics referred to secondary care started in 1983, with review and new entry at 5-yr intervals. The principal outcome measures are: mortality (presented here), best function and therapeutic step. All adult asthmatics with > or = 15% peak flow (PEF) reversibility to > or = 200 l min-1 were included. Socio-demographic variables, PEF and spirometry were recorded prospectively. Best vital capacity (FVC) and PEF were assessed according to protocol. The mortality of the original cohort after 10 yr was expressed as standardized mortality ratio (SMR) against the local population, with history and pulmonary function at entry as explanatory variables. Ninety-five per cent follow-up was achieved in 628 subjects, with 173 deaths (29.1% of those traced). The excess death rate was nearly 50% (SMR 1.47, 95% CI 1.26-1.71), with 56% of deaths due to respiratory disease (expected 10%). After allowance for age and sex, there was a consistent inverse relationship between mortality and entry best FVC, increased risk of death 1.51 (95% CI 1.33-1.72) per 10% deficit of best FVC predicted. The risk of respiratory death was eight times greater, and of non-respiratory death three times greater, in the lowest compared with the highest quartile of best FVC. There were no interactions with smoking, but possible enhancement of the effect in the socially deprived. Best FVC was a particularly powerful predictor of mortality in subjects < 65 years at entry, in whom 64% of the excess deaths occurred. Most of the excess in respiratory deaths was not due to acute severe asthma but to the development of chronic obstructive pulmonary disease (COPD), as defined functionally, irrespective of smoking habit which made no further contribution to mortality.

Symptoms and pulmonary function in asthma.

The relationship between symptoms and pulmonary function in asthma is important if the latter is to be held relevant to management guidelines and their audit. Associations between reported symptoms, pulmonary function and therapy were studied in 824 asthmatics (mean FEV1 75.4% predicted; best FEV1 84.6% predicted; and actual/best peak flow (PEF) 87.5%). Bronchodilator usage (reflecting symptomatic wheeze) was evenly distributed up to eight times daily; 22.5% of subjects had nocturnal disturbance and 46.3% persistent daytime symptoms. The univariate relationships between symptoms and function were generally closer with best rather than actual/best. They were further explored using quintiles of function. Symptoms were consistently less as best function increased, but were highly significantly greater in the fifth than in the third and fourth quintiles of actual/best FEV1. There was a trend to a similar U-shaped relationship of actual/best PEF with nocturnal disturbance and daytime symptoms. Best function is a good determinant of expected symptom load in an asthmatic population. Below 85% actual/best function reflects the prevalence of symptoms. In asymptomatic patients a level of at least 85-90% is a useful check of physiological control but will not exclude some symptomatic patients, irrespective of best function.

Actual over best function as an outcome measure in asthma.

Several guidelines for the management of asthma suggest that actual/best function is a useful outcome measure. This implies accurate assessment of best function, and a standard for the proportion of best function to be achieved. Seventeen clinics observed their practice simultaneously during four periods in 1990. The aims of the study included testing a protocol for the assessment of best function, and validating actual/best function as an outcome measure. The proposed target for actual/best function to indicate satisfactory control was 80%. The protocol for assessment of best function required formal trial of steroids if best function was < 70% predicted; with regular recording of peak expiratory flow (PEF) if < 80% predicted. PEF was recorded in 515 and FEV1 in 680 of 767 subjects, following the usual clinic practice. If the protocol for best function was not satisfied, mean actual/best function was no higher than if it was, except when best PEF was < 70% predicted. This suggests the need for a PEF chart in these latter patients. Best function was greater in females than males, but actual/best function was almost identical. Whilst best function declined with increasing intensity of treatment, actual/best function was almost independent of regimen step, particularly in the centre which most closely adhered to the protocol. These results confirm that actual/best function is a valid outcome measure. Mean actual/best was > 80% except for FEV1 in two centres. It is suggested that the target in chronic management of asthma is raised from 80 to 85% of best, when actual/best PEF is used as a spot check in patients believed to be on optimal therapy.

Use of the allogeneic TCR repertoire to enhance anti-tumor immunity.

It is well established that antigen-specific T lymphocytes can inhibit tumor growth in humans and in mice, leading to complete tumor elimination in some cases. However, in many cases T cell immunity is unable to successfully control tumor progression. Since tumors are derived from normal tissues, most antigens are shared with normal tissues, although expression levels are usually elevated in malignant cells. Nevertheless, low-level expression in normal cells can be sufficient to render autologous T cells tolerant and thus unable to mount effective immune responses against tumors. Here, we review how allogeneic T cells can be used to isolate T cells that effectively recognise and kill tumor cells, but not normal cells with low level of antigen expression. The TCR of allogeneic T cells can be introduced into patient T cells to equip them with anti-tumor specificity that may not be present in the autologous T cell repertoire.

New developments in sensor technology for water quality surveillance and early warning.

Sensor technologies offer particular advantages for surveillance, early warning and process control. This work aimed to provide information about practical new sensing devices that can be used for rapid field assessment of water pollution. A questionnaire completed in 2002 gathered information and data for a catalogue of sensors and instruments that can potentially be applied to soils, sediments, surface and groundwater. Demonstrations of practical sensing technologies took place at a former metal mining site near to Sevilla in 2002, and focusing on diffuse pollution in Koblenz in 2003. These exercises have confirmed that sensors and analytical methodologies can be applied on site to determine various analytes. The instruments provided information useful to manage existing water pollution problems. Some of the scientific innovations of the newest technologies consisted of improved sensitivity, the improved relevance of assays based on biomarkers, the reduced impact on the environment and the capability to detect new contaminants. Sensor technologies were also found to be useful to detect the effects of pollutant mixtures. The portability of these instruments is advantageous for on site and in situ analyses. They will help industry and regulators to deal with existing pollution and attain good water quality.

Peritonitis in continuous ambulatory peritoneal dialysis.

The main complication of continuous ambulatory peritoneal dialysis (CAPD) is peritonitis. This paper describes our experience in the diagnosis and management of this complication in 66 patients during the three years to October 1982. The overall incidence of peritonitis was one episode every 6.75 patient months. Staphylococcus albus and Staphylococcus aureus together accounted for 46 per cent of the episodes, and 24 per cent were culture negative. Catheter exit site infections due to Staphylococcus aureus were common and they may have predisposed to peritonitis with gram -ve organisms as well as to staphylococcal peritonitis. Antimicrobial therapy was effective in 60 per cent of peritonitis episodes. The culture negative episodes usually responded to treatment while those due to fungi, though uncommon, did not. Twenty-nine per cent of these CAPD patients were transferred to haemodialysis because of peritonitis which failed to respond to treatment or which recurred repeatedly.