Results from a Ukrainian-US collaborative study: prevalence and predictors of respiratory symptoms among Ukrainian coal miners.

BACKGROUND: Underground coal mining is an expanding industry in Ukraine, yet little is known about the burden of respiratory disease among Ukrainian miners. METHODS: A Fogarty International Center-supported collaboration between researchers at the University of Illinois and the Institute of Occupational Health in Kyiv, Ukraine formed to improve capacity for conducting and monitoring medical surveillance among Ukrainian coal miners. A cross-sectional survey among a random sample of working and former miners was conducted; demographic, work, and health information were collected using a standardized questionnaire. Weighted prevalence rates were calculated and predictors of respiratory symptoms explored. RESULTS: Improvements in infrastructure, including spirometry and chest radiography testing, transformed medical surveillance among these miners. Results from the health study included that the prevalence of respiratory symptoms was higher among former compared to current miners (shortness of breath 35.6% vs. 5.1%; chronic bronchitis 18.1% vs. 13.9%, respectively). A statistically significant exposure-response relationship was observed between years mining and respiratory symptoms in former miners and between years mining at the coal face and respiratory symptoms among current miners. Evidence of downward bias from the healthy worker survivor effect was observed. CONCLUSIONS: This successful international collaboration built a sustainable infrastructure for conducting workplace medical surveillance and research. The resulting study was the first in the western literature to report on respiratory symptoms in this population; likely underestimation of disease rates due to selection and measurement biases was demonstrated. Efforts should continue to build this collaboration and to characterize and reduce respiratory illness among Ukrainian coal miners.

CD45-null transgenic mice reveal a positive regulatory role for CD45 in early thymocyte development, in the selection of CD4+CD8+ thymocytes, and B cell maturation.

The CD45 transmembrane glycoprotein has been shown to be a protein phosphotyrosine phosphatase and to be important in signal transduction in T and B lymphocytes. We have employed gene targeting to create a strain of transgenic mice that completely lacks expression of all isoforms of CD45. The spleens from CD45-null mice contain approximately twice the number of B cells and one fifth the number of T cells found in normal controls. The increase in B cell numbers is due to the specific expansion of two B cell subpopulations that express high levels of immunoglobulin (IgM) staining. T cell development is significantly inhibited in CD45-null animals at two distinct stages. The efficiency of the development of CD4-CD8- thymocytes into CD4+ CD8+ thymocytes is reduced by twofold, subsequently the frequency of successful maturation of the double positive population into mature, single positive thymocytes is reduced by a further four- to fivefold. In addition, we demonstrate that CD45-null thymocytes are severely impaired in their apoptotic response to cross-linking signals via T cell receptor (TCR) in fetal thymic organ culture. In contrast, apoptosis can be induced normally in CD45-null thymocytes by non-TCR-mediated signals. Since both positive and negative selection require signals through the TCR complex, these findings suggest that CD45 is an important regulator of signal transduction via the TCR complex at multiple stages of T cell development. CD45 is absolutely required for the transmission of mitogenic signals via IgM and IgD. By contrast, CD45-null B cells proliferate as well as wild-type cells to CD40-mediated signals. The proliferation of B cells in response to CD38 cross-linking is significantly reduced but not abolished by the CD45-null mutation. We conclude that CD45 is not required at any stage during the generation of mature peripheral B cells, however its loss reveals a previously unrecognized role for CD45 in the regulation of certain subpopulations of B cells.

Detection of herpes viruses in respiratory secretions of patients undergoing artificial ventilation.

The significance of detection of herpes viruses in respiratory secretions of critically ill patients is controversial. The study aim was to determine the prevalence of herpes virus DNA in respiratory secretions in patients on artificial ventilation. Respiratory secretions taken thrice weekly from 174 patients in a tertiary center intensive therapy unit (ITU) were tested for herpes simplex virus (HSV) by nested PCR. Samples from 61 patients in ITU for 4 days or more were also tested for Epstein Barr Virus (EBV) and cytomegalovirus (CMV) using real-time PCR. HSV positivity increased with ITU stay with 18.6% admission samples positive, 32.5% day 2-5 samples, and 65.9% day 6-39 samples. Being HSV positive on admission did not influence mortality (9/27, 33.3% vs. 38/118, 32.2%) however, subsequently, mortality of those negative but becoming positive was higher than in those remaining negative (10/35, 29% vs. 5/24 21%). At least one sample was EBV positive in 61% and CMV positive in 19% of patients tested. Of 63 patients tested for all three viruses, 4 were positive for three viruses, 23 patients for two viruses, 24 for one virus and 12 were negative for all the above viruses. Detection of HSV, EBV and CMV is common in ITU patients. Becoming HSV positive while in ITU may increase mortality.

Genetic patterns and changes in availability of suitable habitat support a colonisation history of a North American perennial plant.

Climatic fluctuations during the Pleistocene influenced the geographical distribution of plant species across the southern region of California. Following an integrative approach, we combined genetic data analysis with Environmental Niche Models (ENMs) to assess the historical range expansion of Yucca schidigera, a long-lived desert perennial native of the Baja California Peninsula. We genotyped 240 individuals with seven nuclear microsatellite to investigate genetic diversity distribution across 13 populations. Indeed, we used Environmental Niche Models to examine the changes on the distribution of suitable climatic conditions for this species during the LIG (~120 ka), LGM (~22 ka) and Mid Holocene (~6 ka). We detected high genetic diversity across Y. schidigera populations (AR = 9.94 ± 0.38 SE; Hexp = 0.791 ± 0.011 SE) with genetic variation decreasing significantly with latitude (allelic richness: R 2 = 0.38, P = 0.023; expected heterocigosity: R2 = 0.32, P = 0.042). We observed low, but significant genetic differentiation (FST = 0.0678; P < 0.001) which was consistent with the parapatric distribution of the three genetic groupings detected by the Bayesian clustering algorithm. The ENMs suggest that suitable habitat for this species increased since the LGM. Our results support a range expansion of Y. schidigera across northwestern Baja California during the late Quaternary. Genetic data suggest that colonization of the current distribution followed a southward directionality as suitable climatic conditions became widely available in this region. High genetic variation across our sample suggests large historic effective population sizes for this section of the geographical range.

GAP domains responsible for ras p21-dependent inhibition of muscarinic atrial K+ channel currents.

The interaction between the low molecular weight G protein ras p21 and a guanosine triphosphatase activating protein (GAP) uncouples a heterotrimeric G protein (Gk) from muscarinic receptors. Through the use of isolated atrial cell membranes and genetically engineered GAP deletion mutants, the src homology regions (SH2-SH3) at the amino terminus of GAP have been identified as the domains responsible for this effect. Deletion of the domain required to stimulate the guanosine triphosphatase activity of ras p21 relieves the requirement for ras p21 in this system. A model is presented that suggests that ras p21 induces a conformational change in GAP, which allows the SH2-SH3 regions of GAP to function.

Impact of currently used or potentially useful insecticides for canola agroecosystems on Bombus impatiens (Hymenoptera: Apidae), Megachile rotundata (Hymentoptera: Megachilidae), and Osmia lignaria (Hymenoptera: Megachilidae).

Pest management practices may be contributing to a decline in wild bee populations in or near canola (Brassica napus L.) agroecosystems. The objective of this study was to investigate the direct contact toxicity of five technical grade insecticides--imidacloprid, clothianidin, deltamethrin, spinosad, and novaluron--currently used, or with potential for use in canola integrated pest management on bees that may forage in canola: common eastern bumble bees [Bombus impatiens (Cresson); hereafter bumble bees], alfalfa leafcutting bees [Megachile rotundata (F.)], and Osmia lignaria Cresson. Clothianidin and to a lesser extent imidacloprid were highly toxic to all three species, deltamethrin and spinosad were intermediate in toxicity, and novaluron was nontoxic. Bumble bees were generally more tolerant to the direct contact applications > O. lignaria > leafcutting bees. However, differences in relative toxicities between the three species were not consistent, e.g., whereas clothianidin was only 4.9 and 1.3x more toxic, deltamethrin was 53 and 68x more toxic to leafcutting bees than to bumble bees and O. lignaria, respectively. Laboratory assessment of direct contact toxicity, although useful, is only one measure of potential impact, and mortality under field conditions may differ greatly depending on management practices. Research conducted using only honey bees as the indicator species may not adequately reflect the risk posed by insecticides to wild bees because of their unique biology and differential susceptibility. Research programs focused on determining nontarget impact on pollinators should be expanded to include not only the honey bee but also wild bee species representative of the agricultural system under investigation.

CPAN, a human nuclease regulated by the caspase-sensitive inhibitor DFF45.

Induction of apoptosis by death receptors such as Fas or tumour necrosis factor (TNF) R1 leads to distinct changes in cell morphology, activation of the caspase protease cascade, and the degradation of nuclear chromatin by activated nucleases. Here, we describe the purification and cDNA cloning of a novel 40 kDa endonuclease from Jurkat cells that is activated by caspases. This protein, designated caspase-activated nuclease (CPAN), is sufficient to degrade naked DNA and to induce apoptotic morphology and DNA fragmentation in naive nuclei. CPAN is highly homologous to a recently described mouse nuclease, CAD [1], and may represent the human homologue. Our data on the human cDNA as well as additional data on the mouse homologue suggest that a 30 amino-acid portion of the recently published mouse sequence [1] is incorrect. We show that the activity of human CPAN is regulated by DFF45 [2], an inhibitor necessary for CPAN expression and stabilization in an inactive state in living cells. Proteolytic cleavage of DFF45 by caspases in vitro leads to dissociation of DFF45 fragments from CPAN and activation of CPAN as an endonuclease. CPAN is a tightly regulated endonuclease with unique characteristics that might represent a distinctive family of endonucleases.

Localization of the rap1GAP catalytic domain and sites of phosphorylation by mutational analysis.

rap1GAP is a GTPase-activating protein that specifically stimulates the GTP hydrolytic rate of p21rap1. We have defined the catalytic domain of rap1GAP by constructing a series of cDNAs coding for mutant proteins progressively deleted at the amino- and carboxy-terminal ends. Analysis of the purified mutant proteins shows that of 663 amino acid residues, only amino acids 75 to 416 are necessary for full GAP activity. Further truncation at the amino terminus resulted in complete loss of catalytic activity, whereas removal of additional carboxy-terminal residues dramatically accelerated the degradation of the protein in vivo. The catalytic domain we have defined excludes the region of rap1GAP which undergoes phosphorylation on serine residues. We have further defined this phosphoacceptor region of rap1GAP by introducing point mutations at specific serine residues and comparing the phosphopeptide maps of the mutant proteins. Two of the sites of phosphorylation by cyclic AMP (cAMP)-dependent kinase were localized to serine residues 490 and 499, and one site of phosphorylation by p34cdc2 was localized to serine 484. In vivo, rap1GAP undergoes phosphorylation at four distinct sites, two of which appear to be identical to the sites phosphorylated by cAMP-dependent kinase in vitro.

Requirement for posttranslational processing of Rac GTP-binding proteins for activation of human neutrophil NADPH oxidase.

Rac1 and Rac2 are closely related, low molecular weight GTP-binding proteins that have both been implicated in regulation of phagocyte NADPH oxidase. This enzyme system is composed of multiple membrane-bound and cytosolic subunits and when activated catalyzes the one-electron reduction of oxygen to superoxide. Superoxide and its highly reactive derivatives are essential for killing microorganisms. Rac proteins undergo posttranslational processing, primarily the addition of an isoprenyl group to a carboxyl-terminal cysteine residue. We directly compared recombinant Rac1 and Rac2 in a human neutrophil cell-free NADPH oxidase system in which cytosol was replaced by purified recombinant cytosolic components (p47-phox and p67-phox). Processed Rac1 and Rac2 were both highly active in this system and supported comparable rates of superoxide production. Under different cell-free conditions, however, in which suboptimal amounts of cytosol were present in the assay mixture, processed Rac2 worked much better than Rac1 at all but the lowest concentrations. This suggests that a factor in the cytosol may suppress the activity of Rac1 but not of Rac2. Unprocessed Rac proteins were only weakly able to support superoxide generation in either system, but preloading of Rac1 or Rac2 with guanosine 5'-O-(3-thio-triphosphate) (GTP gamma S) restored activity. These results indicate that processing is required for nucleotide exchange but not for interaction with oxidase components.

Aspergillus surveillance project at a large tertiary-care hospital.

A one-year surveillance project was conducted at a large tertiary hospital, which had extensive indoor renovation and extensive demolition/building at several nearby sites. This study collected viable fungi samples in the hospital every six days and analysed 74 duct dust samples for Aspergillus fumigatus mycelial asp f1 protein. Mean total fungi were 257.8 cfu/m3 outdoors, 53.2 cfu/m3 in all indoor samples and 83.5 cfu/m3 in the bone marrow transplant patient rooms. Mean total aspergillus was 6.8 cfu/m3 outdoors, 12.1 cfu/m3 in all indoor samples and 7.3 cfu/m3 in the bone marrow transplant patient rooms. The five most prevalent Aspergillus species collected inside the hospital (mean cfu/m3) were Aspergillus niger 7.57 cfu/m3, Aspergillus candidus 1.72 cfu/m3, Aspergillus flavus 0.97 cfu/m3, A. fumigatus 0.88 cfu/m3 and Aspergillus glaucus 0.45 cfu/m3. In rooms undergoing duct cleaning, mean A. fumigatus concentrations were 11.0 cfu/m3. Forty-eight of 74 (65%) duct dust samples had measurable levels of asp f1 protein, with a mean level of 0.41 ppm and maximum level of 1.94 ppm. Three major incidents involved increased hospital aspergillus concentrations. A. niger levels reached 680 cfu/m3 in an organ transplant room after a water leak from a ceiling pipe. Total aspergillus concentrations rose to 77 cfu/m3 in a bone marrow transplant patient room after improper sealing and water infiltration of the unit's dedicated high-efficiency particulate air filter system. Total aspergillus levels of 160 cfu/m3 were recorded in a renovation area during wood cutting. The higher concentrations of aspergillus seen inside the hospital compared with outdoors and the various moisture/HEPA filter/renovation incidents suggest that numerous small to moderate sources of aspergillus exist in the hospital.

The role of intracellular signalling pathways regulating thymocyte and leukemic T cell apoptosis.

Apoptosis plays a critical role during T cell development, both in the generation of functionally competent T cells in the thymus and the regulation of peripheral T cell populations. The fate of any T cell, whether it is developing in the thymus, or functioning in the peripheral immune system, is dependent on T cell receptor (TCR) specificity for antigens presented by MHC molecules and on the consequences of TCR-generated intracellular signalling pathways which lead to activation, anergy or apoptosis. This review describes data that have elucidated the way in which these highly regulated TCR-derived signalling pathways lead to such diverse final outcomes in thymocytes. Contributions to the induction of apoptosis in thymocytes by signalling pathways and receptors such as Fas, CD45 and CD28 are summarized, particularly with regard to the analysis of relevant transgenic mice. Developments concerning regulation of apoptosis by bcl-2 family members and the possible effectors of apoptosis, proteases, are assessed. Finally, this information is contrasted with the relatively scarce data on signalling pathways in thymic-derived T-ALL cells together with potential explanations of how transformation might occur by perturbation of apoptotic mechanisms. Precise understanding of these pathways may lead to the development of novel therapeutic reagents.

The role of interleukin 6 and interleukin 1 in megakaryocyte development.

The effect of human interleukin 6 (IL-6) and interleukin 1 (IL-1) on cells of the megakaryocyte lineage from murine bone marrow was examined. In bone marrow liquid culture, IL-6 but not IL-1 increases the amount of acetylcholinesterase, a megakaryocyte marker. In semisolid colony assays, a low level of interleukin 3 (IL-3) was used as a growth factor, and IL-6 and IL-1 were tested for their ability to potentiate the activity of IL-3 to stimulate megakaryocyte colony formation. IL-6 and/or IL-1 had no effect on megakaryocyte colony formation in the absence of IL-3. However, IL-6 was able to stimulate increased megakaryocyte colonies in the presence of IL-3. IL-1 was able to potentiate colony formation only in the presence of both IL-3 and IL-6.

Generation of monoclonal antibodies to human lymphocyte cell surface antigens using insect cells expressing recombinant proteins.

We have expressed human CD40 and human B7 in insect cells using the baculovirus expression system and have used these insect cells to immunize mice for the generation of monoclonal antibodies. We demonstrate here that specific monoclonal antibodies to human CD40 and human B7 were obtained using this approach. One significant advantage of this method is that immunizing mice with insect cells did not evoke an immune response to human cells and, therefore, EBV-transformed human B cells could be used to screen for specific antibody production by the hybridoma clones.

Defective depletion of CD45-null thymocytes by the Staphylococcus aureus enterotoxin B superantigen.

The development of a normal T-cell repertoire is critically dependent on the negative and positive selection events which occur at the CD4+CD8+ (double positive, DP) stage of thymic development. Depending on the avidity of the T-cell antigen receptor (TCR) for peptides presented within the thymus, DP thymocytes are either positively selected for maturation to CD4+/CD8+ single positive cells or are depleted by apoptosis. The addition of superantigen to thymocytes within foetal thymic organ culture (FTOC) mimics the negative selection signal of potentially autoreactive thymocytes and induces the responding population of thymocytes to apoptose. Here we present evidence that the transmembrane phosphotyrosine phosphatase CD45 critically regulates TCR-induced signals in thymic differentiation and present data to show defective depletion of CD45-null transgenic TCR-Vbeta8 DP thymocytes in FTOC by the Staphylococcus aureus Enterotoxin B (SEB) superantigen.

Positive tuberculin skin test reactions among house staff at a public hospital in the era of resurgent tuberculosis.

BACKGROUND: The number and significance of tuberculin skin test reactions were compared with self-reported baseline values among house staff working in a public hospital. High-risk medical specialties, locations, and infection control practices were examined. METHODS: House staff interviews, tuberculin skin test applications, review of employee health service records, and environmental monitoring of high-risk areas were performed. RESULTS: Among house staff self-reported as having negative tuberculin skin test status, 46.2% (95% CI 27.0% to 65.4%) of internal medicine house staff, compared with 4.8% (95% CI 4.3% to 13.9%) of house staff from other areas (p < 0.005), had positive results on a repeat tuberculin skin testing before graduation. These differences were not entirely explained by the use of surgical masks, year of training, or previous vaccination with bacille Calmette-Guérin. Most skin test reactions (69%) occurred among house staff who had not been vaccinated with bacille Calmette-Guérin. Increased skin reactivity probably represented excess conversions from unprotected exposure. Tuberculosis transmission was facilitated by delays in diagnosis, inadequate isolation facilities, and suboptimal ventilation. House staff did not comply with recommended tuberculosis surveillance because of time constraints, fear, and misunderstandings about tuberculin skin test interpretations in light of previous bacille Calmette-Guérin vaccination. CONCLUSIONS: House staff in high-exposure settings with suboptimal environmental controls are at increased risk for tuberculosis infection. Participation in surveillance programs can be increased by enlisting the participation and advocacy of respected medical colleagues, screening house staff differentially according to exposure and job classifications, and more accurately interpreting subsequent test results from baseline two-step testing.

Mycobacterium tuberculosis DNA Not Detected by Polymerase Chain Reaction In Air Samples From Hospital Rooms of Tuberculosis Patients.

Background: As the incidence of tuberculosis (TB) increased in the United States, the risk of occupational and nosocomial TB also increased. Airborne Mycobacterium tuberculosis (MTB) is difficult to measure directly. Quantifying MTB DNA by polymerase chain reaction in air samples obtained from isolation rooms of patients with TB would provide a measure of the number of airborne organisms produced by a patient and the efficacy of ventilation, and might predict when an individual patient is no longer infectious. Methods and Results: The air was sampled through cellulose ester filters from the isolation room of a patient with newly diagnosed pulmonary TB, from a patient on therapy for 14 days, and from adjacent offices, and an attempt was made to detect MTB DNA; however, MTB DNA was detected only on positive control filters. Conclusions: Mycobacterium tuberculosis was not detected by polymerase chain reaction in air samples from the rooms of two patients with pulmonary TB. This may have been due to the large number of room air changes with resultant rapid clearance of airborne droplet nuclei or to the limited air volume sampled. A sensitive molecular assay of airborne MTB could be used to monitor the efficacy of infection control measures by sampling a sufficient volume of isolation room air and could aid in determining when an individual patient was no longer infectious.

Fatal falls in the US construction industry, 1990 to 1999.

The Occupational Safety and Health Administration's (OSHA's) Integrated Management Information System (IMIS) database allows for the detailed analysis of risk factors surrounding fatal occupational events. This study used IMIS data to (1) perform a risk factor analysis of fatal construction falls, and (2) assess the impact of the February 1995 29 CFR Part 1926 Subpart M OSHA fall protection regulations for construction by calculating trends in fatal fall rates. In addition, IMIS data on fatal construction falls were compared with data from other occupational fatality surveillance systems. For falls in construction, the study identified several demographic factors that may indicate increased risk. A statistically significant downward trend in fatal falls was evident in all construction and within several construction categories during the decade. Although the study failed to show a statistically significant intervention effect from the new OSHA regulations, it may have lacked the power to do so.

Determination of VOC emission rates and compositions for offset printing.

The release rates of volatile organic compounds (VOC) as fugitive emissions from offset printing are difficult to quantify, and the compositions are usually not known. Tests were conducted at three offset printing shops that varied in size and by process. In each case, the building shell served as the test "enclosure," and air flow and concentration measurements were made at each air entry and exit point. Emission rates and VOC composition were determined during production for (1) a small shop containing three sheetfed presses and two spirit duplicators (36,700 sheets, 47,240 envelopes and letterheads), (2) a medium-size industrial in-house shop with two webfed and three sheetfed presses, and one spirit duplicator (315,130 total sheets), and (3) one print room of a large commercial concern containing three webfed, heatset operations (1.16 x 10(6) ft) served by catalytic air pollution control devices. Each test consisted of 12 one-hour periods over two days. Air samples were collected simultaneously during each period at 7-14 specified locations within each space. The samples were analyzed by gas chromatography (GC) for total VOC and for 13-19 individual organics. Samples of solvents used at each shop were also analyzed by GC. Average VOC emission rates were 4.7-6.1 kg/day for the small sheetfed printing shop, 0.4-0.9 kg/day for the industrial shop, and 79-82 kg/day for the commercial print room. Emission compositions were similar and included benzene, toluene, xylenes, ethylbenzene, and hexane. Comparison of the emission rates with mass balance estimates based on solvent usage and composition were quite consistent.(ABSTRACT TRUNCATED AT 250 WORDS)

Lead, chromium, and cadmium exposure during abrasive blasting.

An evaluation of lead, cadmium, and chromium exposure was conducted during abrasive blasting of a steel bridge to remove paint in preparation for repainting. Airborne lead concentrations were measured at several locations inside the containment structure, as well as near the workers' breathing zones. Airborne cadmium and chromium were also measured in the containment area. Blood lead levels were monitored in each worker. Airborne lead and cadmium levels in containment exceeded the Occupational Safety and Health Administration's permissible exposure limits by factors of 219 and 3.1, respectively. The use of supplied air-blasting helmets will not effectively reduce workers' lead exposure to the permissible exposure limits when airborne levels are as high as were measured in this study. Studies are needed to evaluate additional engineering controls and alternative paint removal methods. Evaluation of workers' exposure to lead and other hazardous metals is needed for projects involving abrasive blasting. Medical surveillance for cadmium and lead may be necessary for similar projects.

Effects of immediate-release opioid on memory functioning: a randomized-controlled study in patients receiving sustained-release opioids.

BACKGROUND: The effects of opioid medication on cognitive functioning in patients with cancer and non-cancer pain remain unclear. METHOD: In this mechanistic randomized, double-blind, placebo-controlled, cross-over study of patients (n = 20) receiving sustained-release and immediate-release opioid medication as part of their palliative care, we examine memory effects of an additional dose of participants' immediate-release medication (oxycodone or morphine) or placebo. Immediate prose recall and recall of related and unrelated word pairs was assessed pre-and post-drug (placebo or immediate-release opioid). Memory for these stimuli was also tested after a delay on each testing occasion. Finally, performance on an 'interference' word pair task was assessed on the two testing occasions since proactive interference has been posited as a mechanism for acute opioid-induced memory impairment. RESULT: Unlike previous work, we found no evidence of memory impairment for material presented before or after individually tailored, 'breakthrough' doses of immediate-release opioid. Furthermore, immediate-release opioid did not result in increased memory interference. On the other hand, we found enhanced performance on the interference word pair task after immediate-release opioid, possibly indicating lower levels of interference. CONCLUSION: These results suggest that carefully titrated immediate-release doses of opioid drugs may not cause extensive memory impairment as previously reported, and in fact, may improve memory in certain circumstances. Importantly, our findings contrast strikingly with those of a study using the same robust design that showed significant memory impairment. We propose that factors, such as depressive symptoms, education level and sustained-release opioid levels may influence whether impairment is observed following immediate-release opioid treatment.