Waveguide lasers in ytterbium-doped tantalum pentoxide on silicon.

A waveguide laser in an ytterbium-doped tantalum pentoxide film is reported. The waveguide is formed of a rib of sputtered tantalum pentoxide on top of oxidized silicon with an over-cladding of silica. Emission at a wavelength of 1025 nm was achieved with an absorbed pump power threshold and slope efficiency of ≈29 mW and 27%, respectively, for a cavity formed by a high reflector mirror and an estimated 12% Fresnel reflection from the bare end-face at the output.

Hollow-bottle optical microresonators.

Selective excitation of whispering-gallery and bottle modes in a robust hollow-bottle optical microresonator, fabricated from a silica microcapillary by a pressure-compensated, "soften-and-compress" method, is demonstrated. Characteristic resonance spectra of bottle modes were obtained by using a tapered fiber coupled at different locations along the hollow bottle. The spectral characteristics (Q-factor, excitation efficiency) are shown to have high tolerance to angular misalignment of the tapered fiber. In addition, introduction of localized losses on the outer surface of the resonator results in selective clean-up of the transmission spectrum and superior performance. A theoretical analysis of modal turning points and associated resonant wavelengths is used to explain the mechanism of mode-suppression and the resultant spectral cleaning.

Whispering gallery mode spectra of channel waveguide coupled microspheres.

Evanescent coupling of light from glass channel waveguides into the whispering gallery modes of glass microspheres of radius 15?m and 100?m is studied experimentally at wavelengths near 1550 nm. Fitting the positions, widths and heights of resonances in the experimental spectra to the characteristic equation for microsphere modes and to universal coupled microresonator theory, we establish sphere radius and index, identify mode numbers, and determine losses. The results provide detailed information for the design of optical devices incorporating microsphere resonators in planar lightwave circuits.

Submicron patterning of DNA oligonucleotides on silicon.

The covalent attachment of DNA oligonucleotides onto crystalline silicon (100) surfaces, in patterns with submicron features, in a straightforward, two-step process is presented. UV light exposure of a hydrogen-terminated silicon (100) surface coated with alkenes functionalized with N-hydroxysuccinimide ester groups resulted in the covalent attachment of the alkene as a monolayer on the surface. Submicron-scale patterning of surfaces was achieved by illumination with an interference pattern obtained by the transmission of 248 nm excimer laser light through a phase mask. The N-hydroxysuccinimide ester surface acted as a template for the subsequent covalent attachment of aminohexyl-modified DNA oligonucleotides. Oligonucleotide patterns, with feature sizes of 500 nm, were reliably produced over large areas. The patterned surfaces were characterized with atomic force microscopy, scanning electron microscopy, epifluorescence microscopy and ellipsometry. Complementary oligonucleotides were hybridized to the surface-attached oligonucleotides with a density of 7 x 10(12) DNA oligonucleotides per square centimetre. The method will offer much potential for the creation of nano- and micro-scale DNA biosensor devices in silicon.

The Cambridge Breast Intensity-modulated Radiotherapy Trial: Comparison of Clinician- versus Patient-reported Outcomes.

AIMS: Breast radiotherapy-associated toxicity is often reported using clinical and photographic assessments. The addition of patient-reported outcome measures (PROMs) is becoming more common. This study investigated the concordance between clinician- and patient-reported outcomes. MATERIALS AND METHODS: The Cambridge Breast Intensity-modulated Radiotherapy (IMRT) trial prospectively collected data on clinician assessment and PROMs at 2 and 5 years after breast radiotherapy. Clinician assessment included physical examination and photographic assessment. PROMs included European Organization for Research and Treatment of Cancer (EORTC) BR23 questionnaire and four breast radiotherapy-specific questions. The correlation between patient and clinician scores were analysed on an independent patient basis using percentage agreement, Cohen's kappa coefficient (k) and Bowker's test of symmetry. The analysis was repeated after stratifying patients based on age, baseline Hospital Anxiety and Depression Score (HADS) and baseline body image score. RESULTS: At 2 and 5 years, a weak level of concordance was seen between the clinician-based assessment and PROMS for all the five toxicity end points (k = 0.05-0.21), with individual patient-based agreement of 32.9-78.3% and a highly discordant Bowker's test of symmetry (P < 0.001). The most frequently reported moderate-severe toxicity by patients was change in breast appearance (14% at both 2 and 5 years), whereas it was breast induration (36% and 25% at 2 and 5 years, respectively) by the clinicians. The lack of concordance was not affected by patient's age, baseline HADS and baseline body image score. CONCLUSIONS: This study found that moderate-severe toxicity reported by patients is low and the overall concordance between clinicians and patients is low. This could be due to methodological limitations or alternatively reflects the subjective nature of PROMs. Incorporation of a patient's perception on treatment-related toxicity will have important implications for treatment decisions and follow-up care.

Integrated optical surface plasmon resonance immunoprobe for simazine detection.

This paper presents the detailed design and characterisation of a regenerable integrated optical surface plasmon resonance immunoprobe as a detector for the triazine herbicide simazine. A sensor design theoretically optimised for use in the aqueous environment is presented and its fabrication described. Experimental results on the sensitivity to changes in bulk refractive index of the analyte and on non-specific binding of ovalbumin are presented. Binding inhibition immunoassays were conducted for simazine and the lower limit of detection determined to be 0.16 microgram/l using anti-simazine IgG antibodies and 0.11 microgram/l using anti-simazine Fab fragments. A sample test cycle of 20 min was established.

Dialysis-induced change in erythrocyte volume: effect on change in blood volume calculated from packed cell volume.

Blood volume (BV) change during hemodialysis is often monitored by packed cell volume (PCV). This assumes erythrocyte volume is constant. We tested this by dialyzing 5 patients for 2 hours against high (154 mmol/l), normal (140 mmol/l) and low (126 mmol/l) dialysate sodium concentrations. Erythrocyte water content, calculated from measured blood and plasma water contents, decreased with high and increased with low dialysate sodium concentrations. Erythrocyte volume, calculated from mean corpuscular hemoglobin concentration (MCHC) decreased 3.8% with high concentration dialysate and increased 2.5% when dialysate concentration was low. These changes correlated significantly (r = 0.80, p less than 0.01) with alterations in plasma sodium. Mean corpuscular volume (MCV), measured with a Coulter-S Plus Counter did not alter because of a methodological artefact. BV change can be calculated from PCV when plasma concentrations of osmotically active substances are changed only if allowance is made for altered erythrocyte volume.

Blood pressure reduced by methylene chloride. A study in spontaneously hypertensive rats.

Effects of methylene chloride (CH2Cl2) on blood pressure (BP), body weight, plasma renin activity, hepatic histological structure of spontaneously hypertensive rats (SHRs) and normotensive control rats (NCRs) were studied. Administration of 0.15 mL/100 g/day CH2Cl2 to SHRs for five days reduced the BP from 172 +/- 7 mm Hg (mean +/- SEM) to 155 +/- 6 mm Hg without changing the plasma renin activity. The same regimen did not change the BP of NCRs. A weekly injection of 0.15 mL/100 g/day of CH2Cl2 for five consecutive weeks failed to significantly alter the BP of either SHRs or NCRs. The polyhalogen, whether administered daily or weekly, did not affect the body weight of either SHRs or NCRs. Administration of CH2Cl2 daily for five days produced an extensive but reversible hepatic centrolobular loss of glycogen in both SHRs and NCRs. No other changes were observed in the livers.

A non-invasive continuous method of measuring blood volume during haemodialysis using optical techniques.

Hypotension during haemodialysis and fluid overload between treatments are major problems for haemodialysis patients. Clinical means of assessing hydration state can be relatively imprecise. We describe a non-invasive method of measuring absolute blood volume (BV) during a mock in vitro haemodialysis session which adds objective information to that assessment. As fluid is removed by ultrafiltration, haemoglobin concentration [Hb] rises proportionately with the fall in BV. An optical monitor clamped across the transparent dialysis tubing gives a continuous readout of near infra-red light transmitted through the blood, and this can be converted to [Hb] values. The net change in BV is the difference between the volume of fluid ultrafiltered and the volume which refills the vascular compartment from the extravascular space. By analysing the change in [Hb] and therefore the change in BV at two different rates of fluid removal, the absolute BV can be determined. The accuracy of this method was tested in vitro. This optical method accurately measures the change in BV over a range of [Hb] from 4 to 15 g/dl and blood circulation pump speeds of 150-300 ml/min. A series of 10 in vitro experiments was performed. The mean relative difference between the measured BV and the calculated BV, was 5.7 +/- 2.5%. This readily repeatable technique can accurately measure BV during a mock in vitro haemodialysis session, thus providing information for the clinical assessment of the hydration state. Information from these experiments will assist in future in vivo studies.

A preliminary study of the measurement of plasma osmotic pressure in equine medicine.

The normal plasma osmotic pressure was established in 205 Thoroughbred horses. Samples taken from horses suffering from a variety of diseases showed that measurement of this parameter might prove a valuable non specific test for assessing the severity of some diseases in which there are alterations in metabolism.

A clinincal evaluation of abdominal paracentesis in the horse.

This paper evaluates the usefulness of abdominal paracentesis as a diagnostic aid in abdominal disease in the horse and in particular considers whether or not it can be effectively utilised as an indication for surgical intervention in cases of colic. The results are based upon peritoneal fluid samples collected from 20 normal horses and from 20 cases of colic and peritonitis. Peritoneal fluid was collected from standing horses by inserting a bovine teat cannula into the horses abdomen through the linea alba after desensitisation of the skin on the ventral midline with local anaesthetic. Usually, from 3-5 ml of fluid could be collected from a normal horse. This was either clear or cloudy white or yellow in colour and contained 3310 +/- 703 leucocytes/ml consisting of 63.81% neutrophils, 1.4 +/- 1.3% monocytes, 13.5 +/- 4.3% mesothelial cells and 21.25% +/- 6.2% lymphocytes. Protein content was 1.29 +/- .4g/100ml. Changes in the volume, colour, cellular constituents and protein content of fluid, characterised abdominal disease. In cases of colic, discolouration of the abdominal fluid was found to be the most consistent, reliable and useful indication of bowel necrosis. This in turn indicated the need for urgent surgical intervention rather than conservative treatment. Discolouration commenced early in the course of the disease even while the segment of bowel involved was still viable. Increased volume of fluid, elevated leucocyte count (statistically significant at the 5% level), increased neutrophil percentage and elevated protein levels were less useful criteria for determining the integrity of the bowel. Similar changes from the normal were also found in cases of peritonitis. Here, however, microscopic examination of cells in a smear of the fluid was more useful, as phagocytosis and abnormal cell types indicating infection or inflammation could be seen readily, and a diagnosis based upon these findings. It was concluded that abdominal paracentesis, although no substitute for thorough clinical examination, was a valuable diagnostic aid for abdominal conditions of the horse.

Blood lead and urinary delta aminolevolonic acid (U-ALA) in the diagnosis of lead toxicosis of dogs.

A comparative evaluation of the usefulness of blood lead and urinary delta aminolevolonic acid estimations in the diagnosis of canine lead poisoning was made in 2 dogs which were given increasing quantities of lead by mouth for extended periods. In both lead administered dogs the blood lead levels remained elevated throughout the experimental period of 18 weeks. This contrasted with the results of U-ALA determinations in which elevated levels were detected only infrequently and at erratic intervals lacking relationship to lead exposure.

Hyperlipaemia in ponies.

The case histories and clinical findings of 15 ponies with hyperlipaemia are presented. The disease was characterised by hyperlipidaemia with inappetance, progressing somnolence, muscle fasciculation, diarrhoea, and ventral oedema as the predominant clinical findings. Post mortem examinations of 12 ponies showed extensive lipidosis and vascular thrombosis with widespread secondary changes. Most cases occurred in late pregnant and early lactating mares in the summer months and it is postulated that the disease was initiated in this group by a falling nutritional plane in the face of high nutrient requirements.

Clinical signs, radiology and tissue lead distribution of dogs administered a mixture of lead chloride, lead bromide and lead sulphate.

Eight-month-old dogs maintained on a high-fat-low-calcium diet were administered a mixture of lead chloride, lead bromide and lead sulphate for prolonged periods at 4 different dose levels. Dogs on high levels of leads showed marked weight loss and gastrointestinal symptoms followed by death. Two dogs on low lead levels developed neurological signs. Radiological investigations showed radiopaque particles in 27 per cent of abdominal radiographs and "lead lines' in the distal radius of 3 dogs. Highest tissue lead levels were found in bones followed by liver and kidney, brain and spinal cord.

Association of breast tumour bed seroma with post-operative complications and late normal tissue toxicity: results from the Cambridge Breast IMRT trial.

AIMS: There are two main surgical techniques for managing the tumour bed after breast cancer excision. Firstly, closing the defect by suturing the cavity walls together and secondly leaving the tumour bed open thus allowing seroma fluid to collect. There is debate regarding which technique is preferable, as it has been reported that a post-operative seroma increase post-operative infection rates and late normal tissue side effects. METHODS: Data from 648 patients who participated in the Cambridge Breast IMRT trial were used. Seromas were identified on axial CT images at the time of radiotherapy planning and graded as not visible/subtle or easily visible. An association was sought between the presence of seroma and the development of post-operative infection, post-operative haematoma and 2 and 5 years normal tissue toxicity (assessed using serial photographs, clinical assessment and self assessment questionnaire). RESULTS: The presence of easily visible seroma was associated with increased risk of post-operative infection (OR = 1.80; p = 0.004) and post-operative haematoma (OR = 2.1; p = 0.02). Breast seroma was an independent risk factor for whole breast induration and tumour bed induration at 2 and 5 years. The presence of breast seroma was also associated with inferior overall cosmesis at 5 years. There was no significant association between the presence of seroma and the development of either breast shrinkage or breast pain. CONCLUSION: The presence of seroma at the time of radiotherapy planning is associated with increased rates of post-operative infection and haematoma. It is also an independent risk factor for late normal tissue toxicity. This study suggests that full thickness surgical closure may be desirable for patients undergoing breast conservation and radiotherapy.

The Cambridge Breast Intensity-modulated Radiotherapy Trial: patient- and treatment-related factors that influence late toxicity.

AIMS: The effect of patient- and treatment-related factors in the development of late normal tissue toxicity after radiotherapy is not yet fully established. The aim of this study was to elucidate the relative importance of such factors in the development of late toxicity after breast-conserving surgery and adjuvant breast radiotherapy. MATERIALS AND METHODS: Patient- and treatment-related factors were analysed in 1014 patients who had received adjuvant radiotherapy to the breast in the Cambridge Breast Intensity-modulated Radiotherapy (IMRT) Trial. Late toxicity data were collected using photographic and clinical assessments and patient-reported questionnaires at 2 years after radiotherapy. RESULTS: On multivariate analysis, a larger breast volume was statistically significantly associated with the development of breast shrinkage assessed by serial photographs (odds ratio per litre increase in breast volume = 1.98, 95% confidence interval 1.41, 2.78; P < 0.0005), telangiectasia (odds ratio = 3.94, 95% confidence interval 2.49, 6.24; P < 0.0005), breast oedema (odds ratio = 3.65, 95% confidence interval 2.54, 5.24; P < 0.0005) and pigmentation (odds ratio = 1.75, 95% confidence interval 1.21, 2.51; P = 0.003). Current smokers had an increased risk of developing pigmentation (odds ratio = 2.09, 95% confidence interval 1.23, 3.54; P = 0.006). Patients with a moderate or poor post-surgical cosmesis had a greatly increased risk of moderate or poor overall cosmesis (odds ratio = 38.19; 95% confidence interval 21.9, 66.7; P < 0.0005). Postoperative infection requiring antibiotics was associated with increased risk of telangiectasia (odds ratio = 3.39, 95% confidence interval 1.94, 5.91; P < 0.0005) and breast oversensitivity (odds ratio = 1.78, 95% confidence interval 1.27, 2.49; P = 0.001). CONCLUSIONS: In this study, the greatest risk factors for the development of late toxicity 2 years after breast-conserving surgery and adjuvant radiotherapy were larger breast volume, baseline pre-radiotherapy surgical cosmesis, postoperative infection and possibly smoking. These factors seem to be more important than relatively small differences in dose inhomogeneity and the addition of boost radiotherapy at 2 years after the completion of radiotherapy. The modification of potentially preventable risk factors, such as postoperative infection and smoking, may limit the development of late toxicity after breast radiotherapy.

Multi-modal particle manipulator to enhance bead-based bioassays.

By sequentially pushing micro-beads towards and away from a sensing surface, we show that ultrasonic radiation forces can be used to enhance the interaction between a functionalised glass surface and polystyrene micro-beads, and identify those that bind to the surface by illuminating bound beads using an evanescent field generated by guided light. The movement towards and immobilisation of streptavidin coated beads onto a biotin functionalised waveguide surface is achieved by using a quarter-wavelength mode pushing beads onto the surface, while the removal of non-specifically bound beads uses a second quarter-wavelength mode which exhibits a kinetic energy maximum at the boundary between the carrier layer and fluid, drawing beads towards this surface. This has been achieved using a multi-modal acoustic device which exhibits both of these quarter-wavelength resonances. Both 1-D acoustic modelling and finite element analysis has been used to design this device and to investigate the spatial uniformity of the field. We demonstrate experimentally that 90% of specifically bound beads remain attached after applying ultrasound, with 80% of non-specifically bound control beads being successfully removed acoustically. This approach overcomes problems associated with lengthy sedimentation processes used for bead-based bioassays and surface (electrostatic) forces, which delay or prevent immobilisation. We explain the potential of this technique in the development of DNA and protein assays in terms of detection speed and multiplexing.