Coherent combining of mid-infrared difference frequency generators.

We report what is, to the best of our knowledge, the first experimental demonstration of coherent combining of two mid-infrared difference frequency generators by active phase control in the continuous-wave regime. Using the phase relation that is inherent to the nonlinear process, we are able to phase lock and combine the idler waves by the sole phase control of one of the pump waves. This control is done by an all-fiber electro-optic modulator. Combining is achieved with an excellent efficiency with a residual phase error of λ/28.

Coherent combining of second-harmonic generators by active phase control of the fundamental waves.

Coherent beam combining by active phase control could be useful for power scaling fiber-laser-pumped optical frequency converters. However, a fast phase modulator operating at the frequency-converted wavelength, a non-standard component, would be necessary. Fortunately, nonlinear conversion processes rely on a phase-matching condition allowing for indirect phase control using standard phase modulators. In this Letter, coherent combining of second-harmonic generators is demonstrated in both birefringent and quasi-phase-matching schemes in CW regime. Phase control operates at the fundamental wavelength, using all-fiber electro-optic modulators. An excellent beam combination is achieved with a residual phase error of λ/30 on the second-harmonic wave.

Multicenter study of environmental contamination with antineoplastic drugs in 33 Canadian hospitals.

PURPOSE: No occupational exposure limit exists for antineoplastic drugs. The main objective of this study was to describe environmental contamination with cyclophosphamide, ifosfamide and methotrexate in pharmacy and patient care areas of Canadian hospitals in 2012. The secondary objective was to compare the 2012 environmental monitoring results with the 2008-2010 results. METHODS: Six standardized sites in the pharmacy and six sites on patient care areas were sampled in each participating center. Samples were analyzed for the presence of cyclophosphamide, ifosfamide and methotrexate by UPLC-MS-MS. The limit of detection (LOD) was 1.8 pg/cm² for cyclophosphamide, 2.2 pg/cm² for ifosfamide and 8.0 pg/cm² for methotrexate. The comparison of surface contamination between the 2008-2010 and 2012 studies was made with the 75th percentile of cyclophosphamide concentration. RESULTS: A total of 33 hospitals participated in the study and 363 samples were collected. Overall, 40 % (147/363) of the samples were positive for cyclophosphamide, 18 % (68/363) were positive for ifosfamide and 5 % (17/363) were positive for methotrexate. In 2012, the 75th percentile value of cyclophosphamide surface concentration was of 9.4 pg/cm², which is four times lower than the 2008-2010 75th percentile of 40 pg/cm². In both studies, the 75th percentile for ifosfamide and methotrexate concentration was lower than the LOD. CONCLUSIONS: Surface contamination by cyclophosphamide, ifosfamide and methotrexate in Canadian hospitals is improving both in terms of the proportions of positive samples and in terms of the surface concentration of antineoplastic drugs. A local 75th percentile value should be use to assess local contamination and interpret local results.

Microsecond fiber laser pumped, single-frequency optical parametric oscillator for trace gas detection.

We report on the first microsecond doubly resonant optical parametric oscillator (OPO). It is based on a nested cavity OPO architecture allowing single longitudinal mode operation and low oscillation threshold (few microjoule). The combination with a master oscillator-power amplifier fiber pump laser provides a versatile optical source widely tunable in the 3.3-3.5 µm range with an adjustable pulse repetition rate (from 40 to 100 kHz), high duty cycle (~10(-2)) and mean power (up to 25 mW in the idler beam). The potential for trace gas sensing applications is demonstrated through photoacoustic detection of atmospheric methane.

Environmental contamination with methotrexate in Canadian community pharmacies.

OBJECTIVES: To evaluate environmental contamination with methotrexate, cyclophosphamide, and ifosfamide in Quebec, Canada, community pharmacies and to describe hazardous drug handling practices in these pharmacies. METHODS: Three standardized sites were sampled in each participating community pharmacy. Samples were analyzed for the presence of cyclophosphamide, ifosfamide, and methotrexate by high-performance liquid chromatography tandem mass spectrometry. The limits of detection were 0.10, 0.12, and 0.41 ng/mL for cyclophosphamide, ifosfamide, and methotrexate, respectively. Nine working practices were assessed. RESULTS: 20 community pharmacies participated in the study, and 60 samples were analyzed. No traces of cyclophosphamide or ifosfamide were detected. Traces of methotrexate were found in 12 of 20 pharmacies (60%). Of the 20 pharmacies, 8 (40%) had a storage space reserved for hazardous drugs and none had a preparation area reserved for handling methotrexate tablets. All of the participating community pharmacies had a tablet counter reserved for the handling of hazardous drugs, and all pharmacies cleaned their tablet counter reserved for handling hazardous drugs after use. None of the pharmacies cut or crushed methotrexate tablets. CONCLUSION: The growing number of hazardous drugs represents a challenge for community pharmacies. Community pharmacists must be made aware of their presence and the need to comply with personal protection measures to reduce staff occupational exposure to hazardous drugs.

Environmental contamination with hazardous drugs in quebec hospitals.

BACKGROUND: Since publication of the US National Institute for Occupational Safety and Health alert on hazardous drugs in 2004, many health care organizations have reviewed their procedures for handling hazardous drugs. Occupational exposure may occur when handling, compounding, or administering a drug considered to be hazardous, at any stage from storage to waste management. OBJECTIVES: To describe environmental contamination with cyclophosphamide, ifosfamide, and methotrexate in pharmacy and patient care areas of Quebec hospitals. METHODS: Sixty-eight hospitals were invited to participate. At each hospital, 12 prespecified measurement sites (6 each within pharmacy and patient care areas) were sampled once (midweek, end of day). The samples were analyzed by ultra-performance liquid chromatography tandem mass spectrometry to determine the presence of the 3 drugs. The limits of detection (LODs) were 0.0015 ng/cm(2) for cyclophosphamide, 0.0012 ng/cm(2) for ifosfamide, and 0.0060 ng/cm(2) for methotrexate. RESULTS: Twenty-five (37%) of the hospitals agreed to participate. Samples from sites other than the 12 prespecified sites were excluded. Overall, 259 valid samples were collected between April 2008 and January 2010 (147 samples from pharmacy areas in 25 hospitals and 112 samples from patient care areas in 24 hospitals). No hospital was using a closed-system drug transfer device at the time of the study. The median (minimum, maximum) number of sites per hospital with at least 1 positive sample for at least 1 of the 3 hazardous drugs was 6 (1, 12). A total of 135 (52%) samples were positive for cyclophosphamide, 53 (20%) for ifosfamide, and 7 (3%) for methotrexate. The median (minimum, maximum) concentration in positive samples was 0.0035 ng/cm(2) (below LOD, 28 ng/cm(2)) for cyclophosphamide, below LOD (below LOD, 8.6 ng/cm(2)) for ifosfamide, and below LOD (below LOD, 0.58 ng/cm(2)) for methotrexate. CONCLUSIONS: The levels of environmental contamination with 3 hazardous drugs in this multicentre study were similar to or below those in most published studies. Periodic measurement of surface contamination is necessary to ensure that current practices limit occupational exposure to hazardous drugs.

Picosecond tunable mode locking of a Cr2+:ZnSe laser with a nonlinear mirror.

We report on a nonlinear mirror (NLM) scheme that enables, for the first time to the best of our best knowledge, tunable mode locking of a Cr2+:ZnSe laser in the picosecond regime. The NLM-used as the output coupler of the laser cavity-consists of a periodically poled lithium niobate (PPLN) crystal with a fan-out grating coupled with a dichroic mirror and a wedged dispersive YAG plate. The Cr2+:ZnSe laser, pumped by a CW thulium-doped fiber laser, delivers 85 ps pulses at a repetition rate of 220 MHz with a 300 mW average power. Thanks to the use of a fan-out PPLN crystal, we benefit from the wide tunability of the Cr2+:ZnSe laser and achieve mode locking over the whole 2.44-2.55 µm range while maintaining a narrow-linewidth emission suitable for time-resolved nonlinear spectroscopy applications.

Management of thermal effects in high-repetition-rate pulsed optical parametric oscillators.

We report on the investigation of thermal effects in high-repetition-rate pulsed optical parametric oscillators emitting in the mid-IR. We find that the thermal load induced by the nonresonant idler absorption plays a critical role in the emergence of thermally induced bistability. We then demonstrate a significant improvement of the conversion efficiency (more than 30%) when a proper axial temperature gradient is applied to the nonlinear crystal by use of a two-zone temperature-controlled oven.

Picosecond synchronously pumped ZnGeP2 optical parametric oscillator.

We report on the experimental operation of a picosecond, singly resonant, synchronously pumped optical parametric oscillator (SPOPO) based on a ZnGeP(2) (ZGP) crystal. The ZGP SPOPO is pumped with the idler radiation from a diffraction-grating-tuned periodically poled lithium niobate SPOPO emitting a continuous picosecond pulse train (Delta tau approximately 8 ps, f=76 MHz). The noncritically 90 degree phase-matched ZGP SPOPO is tuned in the 3.8-5.6 microm range by tuning the pump wavelength (2.25-2.5 microm). As high as approximately 800 mW of average power is emitted at 4 microm.

Evaluation of the usefulness of an oxycodone immunoassay in combination with a traditional opiate immunoassay for the screening of opiates in urine.

Oxycodone is a semisynthetic opioid analgesic largely prescribed for post-operative and chronic pain management. The introduction of a slow release formulation of oxycodone has led to its frequent abuse and to an increase in emergency cases related to oxycodone overdose. Until recently, oxycodone testing has been confined to gas chromatography-mass spectrometry (GC-MS) analysis because the widely used automated opiate immunoassays poorly react to this compound. We investigated the utility of a new oxycodone immunoassay as a screening procedure to eliminate inappropriate GC-MS testing of negative urine specimens. We analyzed 96 urine specimens using GC-MS and two immunoassays, CEDIA((R)) opiates and DRI((R)) oxycodone assays from Microgenics, on a Hitachi 917 analyzer. The GC-MS allowed us to detect codeine, hydrocodone, hydromorphone, morphine, oxycodone, and oxymorphone following enzymatic hydrolysis and derivation by acetylation. The combination of the two immunoassays gave the best performance (98% sensitivity and specificity) when considering a positive result from GC-MS for any of the opiates. Considering positive GC-MS results for oxycodone or oxymorphone only, the oxycodone immunoassay resulted in two false-positives and one false-negative (50 ng/mL cutoff). Using these immunoassays for screening before GC-MS analysis provides a reduced opiate GC-MS workload without compromising quality.

Pilot study comparing the efficacy of two cleaning techniques in reducing environmental contamination with cyclophosphamide.

OBJECTIVE: Compare the efficacy of the cleaning technique usually employed in our healthcare facility to eliminate environmental contamination with cyclophosphamide with that of the Surface Safe commercial kit. METHODS: This is a three-step evaluative and comparative study involving: (i) the voluntary contamination of the surface of a hood with a pre-established quantity of cyclophosphamide (20,000,000 ng), (ii) the cleaning of the work surface of the hood using a cleaning technique usually employed in our healthcare facility or that of the product Surface Safe, and (iii) the quantification of cyclophosphamide detected on the work surface. The usual cleaning technique involves the use of a mixture of 0.05% chlorhexidine and 70% ethyl alcohol to clean surfaces, whereas the product Surface Safe involves a combined two-step sodium hypochlorite and sodium thiosulfate wash. RESULTS: The median concentrations of cyclophosphamide detected after the use of the usual technique and the product Surface Safe came to 165 ng cm(-2) (40-570) and 65 ng cm(-2) (57-110), respectively. The results obtained showed an average 99.5% efficacy in reducing the quantity of cyclophosphamide (ng) detected on the work surface for each of the two techniques that were evaluated. CONCLUSION: The study demonstrates that reducing the residual concentration of cyclophosphamide on work surfaces to levels lower than 1 ng cm(-2) remains difficult despite the use of cleaning techniques with a high percentage of efficacy. It stressed the importance of combining two successive cleaning techniques to maximally restrict the residual concentration of hazardous drugs and suggests the use of a combination of sodium hypochlorite and sodium thiosulfate to best reduce environmental contamination levels.

High-energy single-longitudinal mode nearly diffraction-limited optical parametric source with 3 MHz frequency stability for CO2 DIAL.

We report on a 2.05 microm nanosecond master oscillator power amplifier optical parametric source for CO2 differential-absorption lidar. The master oscillator consists of an entangled-cavity nanosecond optical parametric oscillator based on a type II periodically poled lithium niobate crystal that provides highly stable single-longitudinal-mode radiation. The signal emission is amplified by a multistage parametric amplifier to generate up to 11 mJ in a nearly diffraction-limited beam with an M2 quality factor of approximately 1.5 while maintaining single-longitudinal-mode emission with a frequency stability better than 3 MHz rms. This approach can be readily applied to the detection of various greenhouse gases.

Evaluation of surface contamination in a hospital hematology--oncology pharmacy.

OBJECTIVE: To describe environmental contamination with hazardous drugs in a hospital pharmacy setting before and after reorganizing a hematology- oncology satellite pharmacy. METHODS: This is a descriptive study of surface contamination with cyclophosphamide, ifosfamide, and methotrexate in two hematology-oncology satellite pharmacies. In order to measure surface contamination with hazardous drugs, samples from four distinct measurement sites within the pharmacy were taken in each of the two phases (pre-and postphases) using a sampling procedure and an analytical method modified from Larson et al. RESULTS: A total of 133 samples from four measurement sites were taken and analyzed over the course of the study (specifically 60 prephase samples and 73 postphase samples). The study showed a significant increase in the number of positive samples (from 66.7% to 90.4%, p<0.001) from the pre- to the postphase. The increase, however, is only significant in terms of the location where completed preparations were placed after they had come out from under the hood (from 0/15 to 21/28, p<0.001) and the work surface (from 8/15 to 15/15, p=0.006) and only in terms of ifosfamide. Furthermore, for the other sites studied, the number of positive samples remained unchanged between the pre- and postphase. A statistically significant difference between the pre- and postphase was observed in terms of ifosfamide for three of the four measurement sites studied and methotrexate for one of the four sites. Average concentrations were higher in the post phase in three of the four cases. CONCLUSION: This study describes environmental contamination with hazardous drugs in a hospital pharmacy setting before and after reorganizing a hematology-oncology satellite pharmacy. The study showed that a refitting of the hemato-oncology pharmacy is not a sufficient strategy to reduce the environmental contamination by ifosfamide because a significant increase in the number of positive samples from the pre- to the postphase have been observed. Many factors can contribute to influence the contamination of hazardous drugs such as the workflow and the training of the personal. Continuous environmental surveillance of hazardous drugs is required to document traces and help reduce risks.

Cyclophosphamide contamination observed on the external surfaces of drug vials and the efficacy of cleaning on vial contamination.

OBJECTIVE: Evaluate contamination on the external surfaces of cyclophosphamide vials available on the Canadian market during storage in pharmacy departments and the efficacy of decontaminating the external surfaces of vials using various cleaning techniques. METHODS: The study consisted of three phases: the quantification of cyclophosphamide on the external surfaces of 10 vials of Procytox and 10 vials of Cytoxan available on the Canadian market with or without prewashing (Phases I and II) and the quantification of cyclophosphamide on the surfaces of 30 deliberately contaminated empty sterile vials cleaned using three different washing techniques (Phase III). The quantification of cyclophosphamide was conducted using ultra performance liquid chromatography with tandem mass spectrometry. RESULTS: In Phase I, we observed that 9 of 10 vials of Procytox and 4 of 10 vials of Cytoxan had traces of cyclophosphamide. The average concentration of cyclophosphamide measured on the vials was higher for Procytox than it was for Cytoxan. In Phase II, we observed that simply by washing vials with water we could effectively eliminate the presence of contamination on 6 of 10 Procytox vials and on 10 of 10 Cytoxan vials. Phase III demonstrated the efficacy of using a cloth soaked in soapy water to clean the contaminated vials. CONCLUSION: This pilot study demonstrates the presence of contamination on the external surfaces of cyclophosphamide vials from two manufacturers on the Canadian market. It suggests that cleaning vials from manufacturers and wholesalers may help to reduce the risk of occupational exposure. There is a need for a pilot study to establish guidelines on decontamination agents and cleaning process to eliminate the presence of contamination on vial surfaces.

Unproven ingestion: an unrecognized bias in toxicological case series.

BACKGROUND: Case series of ingestion in preschool children may include patients without significant exposure if the substance is not measured. METHODS: In order to evaluate the unproven ingestion bias, we conducted, between January 2000 and June 2004, a retrospective analysis of a poison control center-based series of children <6 years old with a history of toxic methanol or ethylene glycol ingestion. RESULTS: Over the 54 month period, 115 children were referred to obtain a level. Of these, 102 children, aged 25 +/- 10 months, actually had a level analyzed. Only 21 patients had positive levels measured a median of 90 minutes post-ingestion. CONCLUSION: Our findings suggest that a significant fraction of purported cases were not confirmed. When a study aims at determining the toxicity of the substance, measurements of the xenobiotic should be required in any case series involving preschool aged children in order to decrease the unproven ingestion bias.

Active mode locking of continuous-wave doubly and singly resonant optical parametric oscillators.

We report on what we believe to be the first active mode locking of near-degenerate, doubly and singly resonant cw-pumped optical parametric oscillators (OPOs). We show experimentally that a steady-state regime of short pulses is reached in a few tens of microseconds under cw pumping. The oscillation buildup dynamics of both OPOs is also explored, evidencing an unusual transient behavior in the mode-locking process.

Actively mode-locked optical parametric oscillator.

We report on what we believe to be the first demonstration of active mode locking of an optical parametric oscillator. An acousto-optic modulator is inserted into a nearly degenerate (approximately 1064 nm) and doubly resonant optical parametric oscillator based on periodically poled LiNbO3 and pumped with the second harmonic of a quasi-continuous-wave single-frequency Nd:YAG laser. When the modulation frequency is matched to the free spectral range of the cavity (120 MHz), a pulsed regime is observed, with pulse durations as short as 700 ps.

Generation of mid-infrared radiation by self-difference frequency mixing in chromium-doped zinc selenide.

We report what we believe to be the first demonstration of mid-infrared generation (approximately 9 microm) by self-difference frequency generation in Fresnel birefringence quasi-phase-matched Cr:ZnSe laser slabs.

Vitamin A concentration in umbilical cord blood of infants from three separate regions of the province of Québec (Canada).

BACKGROUND: Inuit women from Northern Québec have been shown to consume inadequate quantities of vitamin A. This study was conducted to evaluate the prevalence of blood vitamin A deficiency in newborns from 3 distinct populations of the province of Québec. METHODS: 594 newborns were included in this study (375 Inuit newborns from northern Québec (Nunavik), 107 Caucasian and Native newborns from the Lower Northern Shore of the Saint-Lawrence River (LNS) and 112 newborns from Southern Québec where clinical vitamin A deficiency is uncommon). Mothers were recruited at delivery and vitamin A (retinol) was analyzed from umbilical cord blood samples by reversed-phase high-pressure liquid chromatography. RESULTS: Nunavik and LNS newborns had significantly lower mean vitamin A concentrations in cord blood compared to Southern Québec participants (15.7 microg/dL, 16.8 microg/dL and 20.4 microg/dL respectively). The differences observed were similar when adjusted for sex and birthweight. Results also showed that 8.5% of Nunavik newborns and 12.2% of LNS newborns were below 10.0 microg/dL, a level thought to be indicative of blood vitamin A deficiency in neonates. CONCLUSION: These data suggest that a carefully planned vitamin A supplementation program during pregnancy in Nunavik and LNS might be indicated to promote healthy infant development.