High precision optical cavity length and width measurements using double modulation.

We use doubly phase modulated light to measure both the length and the linewidth of an optical resonator with high precision. The first modulation is at RF frequencies and is set near a multiple of the free spectral range, whereas the second modulation is at audio frequencies to eliminate offset errors at DC. The light in transmission or in reflection of the optical resonator is demodulated while sweeping the RF frequency over the optical resonance. We derive expressions for the demodulated power in transmission, and show that the zero crossings of the demodulated signal in transmission serve as a precise measure of the cavity linewidth at half maximum intensity. We demonstrate the technique on two resonant cavities, with lengths 16 m and a 4 km, and achieve an absolute length accuracy as low as 70 ppb. The cavity width for the 16 m cavity was determined with an accuracy of approximately 6000 ppm. Through an analysis of the systematic errors we show that this result could be substantially improved with the reduction of technical sources of uncertainty.

Stabilized high-power laser system for the gravitational wave detector advanced LIGO.

An ultra-stable, high-power cw Nd:YAG laser system, developed for the ground-based gravitational wave detector Advanced LIGO (Laser Interferometer Gravitational-Wave Observatory), was comprehensively characterized. Laser power, frequency, beam pointing and beam quality were simultaneously stabilized using different active and passive schemes. The output beam, the performance of the stabilization, and the cross-coupling between different stabilization feedback control loops were characterized and found to fulfill most design requirements. The employed stabilization schemes and the achieved performance are of relevance to many high-precision optical experiments.

The Advanced LIGO photon calibrators.

The two interferometers of the Laser Interferometry Gravitational-wave Observatory (LIGO) recently detected gravitational waves from the mergers of binary black hole systems. Accurate calibration of the output of these detectors was crucial for the observation of these events and the extraction of parameters of the sources. The principal tools used to calibrate the responses of the second-generation (Advanced) LIGO detectors to gravitational waves are systems based on radiation pressure and referred to as photon calibrators. These systems, which were completely redesigned for Advanced LIGO, include several significant upgrades that enable them to meet the calibration requirements of second-generation gravitational wave detectors in the new era of gravitational-wave astronomy. We report on the design, implementation, and operation of these Advanced LIGO photon calibrators that are currently providing fiducial displacements on the order of 10-18m/Hz with accuracy and precision of better than 1%.

Gilbert's syndrome and drug metabolism.

Gilbert's syndrome is an inherited disorder which is characterised by unconjugated hyperbilirubinaemia. In patients with Gilbert's syndrome, both bilirubin clearance and in vitro hepatic microsomal uridine diphosphoglucuronyl transferase (UDPGT) activity are reduced. In addition, there is evidence suggesting impaired hepatic uptake of bilirubin in Gilbert's syndrome. Glucuronidation of a number of substrates appears to be impaired in Gilbert's syndrome, but the significance of the reported changes in oxidation and acetylation are less clear.

Survey of neurological problems with amiodarone in the New Zealand Intensive Medicines Monitoring Programme.

Early in the monitoring of amiodarone it was evident that neurological events were unexpectedly frequent. A survey was then undertaken to measure the frequency of such events and to gain some impression of their clinical importance. The method of survey was the completion of questionnaires by doctors when patients were being reviewed. There was a 63.6% response rate and questionnaires were evaluated for 408 patients. There were 192 events assessed as being adverse reactions from a group of nine types of neurological events in 112 patients. Paraesthesiae, ataxia, vertigo and tremor were the most common (7-9%). The overall rate of neurological reactions was 27.5%. The individual reactions are examined as are dose relationships.

Thermal effects in the Input Optics of the Enhanced Laser Interferometer Gravitational-Wave Observatory interferometers.

We present the design and performance of the LIGO Input Optics subsystem as implemented for the sixth science run of the LIGO interferometers. The Initial LIGO Input Optics experienced thermal side effects when operating with 7 W input power. We designed, built, and implemented improved versions of the Input Optics for Enhanced LIGO, an incremental upgrade to the Initial LIGO interferometers, designed to run with 30 W input power. At four times the power of Initial LIGO, the Enhanced LIGO Input Optics demonstrated improved performance including better optical isolation, less thermal drift, minimal thermal lensing, and higher optical efficiency. The success of the Input Optics design fosters confidence for its ability to perform well in Advanced LIGO.

Pneumonitis associated with leflunomide: a profile of New Zealand and Australian reports.

BACKGROUND: Pneumonitis has very rarely been observed in patients taking leflunomide in clinical trials. Evidence is emerging that it is more frequent in clinical practice. AIM: The aim of this study was to investigate voluntary reports of suspected respiratory reactions to leflunomide held by the New Zealand Pharmacovigilance Centre (NZPhvC) and the Australian Adverse Drug Reactions Unit (ADRU) to ascertain if they fulfilled the criteria for pneumonitis and to define characteristics of this reaction. METHOD: Reports of respiratory adverse reactions attributed to leflunomide and received by the NZPhvC and the ADRU were analysed to identify those that were likely to be pneumonitis based on the criteria of Searles and McKendry. Features of these reports were examined to provide further information about this adverse reaction. RESULTS: The NZPhvC and the ADRU received 14 reports considered to be pneumonitis occurring in patients taking leflunomide. Two case reports fulfilled the Searles and McKendry criteria for definite or probable hypersensitivity pneumonitis. The patients in the remaining reports had radiological evidence of pulmonary infiltrates, an acute respiratory illness and no evidence of precipitating infection. In two cases the patients were taking leflunomide alone; one improved when it was withdrawn. In the other 12 cases, patients were taking leflunomide in combination with methotrexate. In nine of these 12 patients pneumonitis occurred after leflunomide was added to methotrexate, usually within 12-20 weeks. One of the two patients who died had possible previous methotrexate pneumonitis. Leflunomide washout with cholestyramine was used to treat three patients, one with life-threatening illness, with good results. CONCLUSION: This case series supports observations that leflunomide can cause pneumonitis either as monotherapy or in combination with methotrexate. The case histories indicate that prompt recognition is important to avoid life-threatening disease and support the use of cholestyramine to remove leflunomide.

Paracetamol (acetaminophen) kinetics in patients with Gilber's syndrome.

The pahrmacokinetics of paracetamol after intravenous and oral administration has been studied in 6 patients with Gilbert's syndrome, and 6 healthy controls. Paracetamol clearance was significantly less in the patients (255 ml/min SE +/- 23 ml/min) than in the normal subjects (352 ml/min SE +/- 40 ml/min). Moreover, whilst paracetamol concentrations declined monoexponentially in the patients, the decline was biexponential in the controls. No difference in the bioavailability of 500 mg paracetamol given orally was observed between the two groups. The results suggest that not only is paracetamol elimination impaired in Gilbert's syndrome, but that its distribution kinetics are also abnormal. Both these findings could be attributed to a decrease in hepatic glucuronyl transferase activity.

Variation in the risk of peptic ulcer complications with nonsteroidal antiinflammatory drug therapy.

OBJECTIVE: To assess the risk of perforation or hemorrhage of peptic ulcer on treatment with nonsteroidal antiinflammatory drugs (NSAIDs), both as a class and as individual agents. METHODS: A case-control study of medication histories in 494 patients and 972 matched control subjects. RESULTS: The increase in risk (odds ratio) with NSAID therapy was 5.1 times the risk in controls. The odds ratio for piroxicam was 6.3 (95% confidence interval [CI] 3.3-12.0), as compared with 2.9 for diclofenac, ketoprofen, and sulindac combined (95% CI 2.0-4.2). The effect of other risk factors was also considered, and the adjusted odds ratios were 4.1 for all NSAIDs, 6.4 (95% CI 2.8-15.0) for piroxicam, and 3.3 (95% CI 2.0-5.5) for diclofenac, ketoprofen, and sulindac combined. CONCLUSION: The estimate of overall risk of peptic ulcer complications with NSAIDs is similar to that found in other studies. There appear to be differences in risk between agents.

Spatial and temporal filtering of a 10-W Nd:YAG laser with a Fabry--Perot ring-cavity premode cleaner.

We report on the use of a fixed-spacer Fabry-Perot ring cavity to filter spatially and temporally a 10-W laser-diode-pumped Nd:YAG master-oscillator power amplifier. The spatial filtering leads to a 7.6-W TEM (00) beam with 0.1% higher-order transverse mode content. The temporal filtering reduces the relative power fluctuations at 10 MHz to 2.8x10(-9)/ radicalHz, which is 1 dB above the shot-noise limit for 50 mA of detected photocurrent.

Comprehensive clinical drug information service: first year's experience.

A comprehensive clinical drug information service, established in the Northern Region in May 1975, is manned by eight doctors--all clinical pharmacologists--and is available 24 hours a day. In the first year of operation 451 inquiries were received, 354 (78-5%) of which were "consultative." Though junior hospital doctors used the service most, almost half of the inquiries about adverse reactions to drugs came from consultants.