Diverse psychotropic substances detected in drug and drug administration equipment samples submitted to drug checking services in Toronto, Ontario, Canada, October 2019-April 2020.

BACKGROUND: The overdose crisis has generated innovative harm reduction and drug market monitoring strategies. In Toronto, Ontario, Canada, a multi-site drug checking service (DCS) pilot project was launched in October 2019. The project provides people who use drugs with information on the chemical composition of their substances, thereby increasing their capacity to make more informed decisions about their drug use and avoid overdose. DCS also provides real-time market monitoring to identify trends in the unregulated drug supply. METHODS: Sample data were obtained through analyses of drug and used drug administration equipment samples submitted anonymously and free of charge to DCS in downtown Toronto from October 10, 2019, to April 9, 2020, representing the first six months of DCS implementation. Analyses were conducted in clinical laboratories using liquid chromatography- and/or gas chromatography-mass spectrometry (LC-MS, GC-MS) techniques. RESULTS: Overall, 555 samples were submitted, with 49% (271) of samples that were found to contain high-potency opioids, of which 87% (235) also contained stimulants. Benzodiazepine-type drugs were found in 21% (116) of all samples, and synthetic cannabinoids in 1% (7) of all samples. Negative effects (including overdose, adverse health events, and extreme sedation) were reported for 11% (59) of samples submitted for analysis. CONCLUSIONS: Toronto's DCS identified a range of high-potency opioids with stimulants, benzodiazepine-type drugs, and a synthetic cannabinoid, AMB-FUBINACA. This information can inform a range of evidence-informed overdose prevention efforts.

Xylazine detected in unregulated opioids and drug administration equipment in Toronto, Canada: clinical and social implications.

BACKGROUND: The North American opioid overdose crisis is driven in large part by the presence of unknown psychoactive adulterants in the dynamic, unregulated drug supply. We herein report the first detection of the psychoactive veterinary compound xylazine in Toronto, the largest urban center in Canada, by the city's drug checking service. METHODS: Toronto's Drug Checking Service launched in October 2019. Between then and February 2021, 2263 samples were submitted for analysis. The service is offered voluntarily at harm reduction agencies that include supervised consumption services. Samples were analyzed using gas chromatography-mass spectrometry or liquid chromatography-high resolution mass spectrometry. Targeted and/or untargeted screens for psychoactive substances were undertaken. RESULTS: In September 2020, xylazine was first detected by Toronto's Drug Checking Service. Among samples analyzed from September 2020 to February 2021 expected to contain fentanyl in isolation (610) or in combination with methamphetamine (16), xylazine was detected in 46 samples (7.2% and 12.5% of samples, respectively). Samples were predominantly drawn from used drug equipment. Three of the samples containing xylazine (6.5%) were associated with an overdose. CONCLUSION: We present the first detection of xylazine in Toronto, North America's fourth-largest metropolitan area. The increased risk of overdose associated with use of xylazine and its detection within our setting highlights the importance of drug checking services in supporting rapid responses to the emergence of potentially harmful adulterants. These data also highlight the clinical challenges presented by the dynamic nature of unregulated drug markets and the concomitant need to establish regulatory structures to reduce their contribution to overdose morbidity and mortality.

Carfentanil structural analogs found in street drugs by paper spray mass spectrometry and their characterization by high-resolution mass spectrometry.

Carfentanil is one of the most potent synthetic opioids ever developed, with an estimated analgesic potency approximately 20-100 times that of fentanyl and 10,000 times that of morphine. Carfentanil has been appearing in the illicit drug supply in many regions and has been linked to fatal overdose events. A subset of 59 street drug samples obtained in Victoria, B.C., that were confirmed to contain carfentanil were analyzed by mass spectrometry for this study. Carfentanil quantitation by paper spray mass spectrometry ranged from 0.05 to 2.95 w/w% (median = 0.32%) in the original drug sample. Paper spray mass spectrometry analysis also detected two unknown peaks at m/z 380.2 and 381.2 in 31 of these 59 samples (53%). Initial tandem mass spectrometry experiments revealed structural similarities between these unknown compounds and carfentanil, suggesting they were potential structural analogs, possibly arising from incomplete purification during synthesis. High-resolution mass spectrometry determined the chemical formulas of these compounds as C23 H29 N3 O2 (m/z 380.2333) and C23 H29 N2 O3 (m/z 381.2137). Literature and tandem mass spectrometry results were used to determine the identity of these potential new psychoactive substances, C23 H29 N3 O2 as desmethylcarfentanil amide and C23 H29 N2 O3 as desmethylcarfentanil acid. µ-Opioid receptor binding modeling determined that the binding poses of these analogs were nearly identical to that of carfentanil with relative binding energy calculations of 0.544 kJ/mol (desmethylcarfentanil amide) and -0.171 kJ/mol (desmethylcarfentanil acid); these data suggest they may share the toxic effects of carfentanil and have similar potencies.

Routine Assessment of Patient Index Data 3 (RAPID3) in Patients with Rheumatoid Arthritis Treated with Long-Term Upadacitinib Therapy in Five Randomized Controlled Trials.

INTRODUCTION: The Routine Assessment of Patient Index Data 3 (RAPID3) is a patient-reported outcome tool recommended for the assessment of disease activity in patients with rheumatoid arthritis (RA) in clinical practice. This analysis evaluated the long-term effect of upadacitinib vs. comparators on RAPID3 scores in patients with RA in the phase 3 SELECT clinical trial program. METHODS: This post hoc analysis included data from five randomized controlled trials (RCTs) in patients receiving upadacitinib 15 mg or 30 mg once daily (QD) as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). The proportions of patients reporting RAPID3 remission (scores ≤ 3) were assessed at week 60. Correlations between absolute scores for RAPID3 and Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), and 28-joint Disease Activity Score with C-reactive protein (DAS28[CRP]) at week 60 were assessed using Spearman correlation coefficients. RESULTS: A total of 3117 patients were included from the SELECT-NEXT, -BEYOND, -MONOTHERAPY, -COMPARE, and -EARLY trials. By week 60, 32-52% of methotrexate-naïve and csDMARD inadequate responder (IR) patients treated with either upadacitinib 15 mg QD or upadacitinib 30 mg QD reported RAPID3 scores consistent with remission. The proportions were slightly lower in the biologic DMARD-IR SELECT-BEYOND population (19-28%). RAPID3 scores highly correlated (Spearman correlation values ≥ 0.58) with CDAI, SDAI, and DAS28(CRP) scores through week 60 (all p < 0.001). CONCLUSIONS: Upadacitinib, as monotherapy or in combination with csDMARDs, was associated with patient-reported remission assessed by RAPID3 over 60 weeks across the SELECT RCTs in patients with RA. TRIAL REGISTRATION: SELECT-BEYOND (NCT02706847); SELECT-NEXT (NCT02675426); SELECT-MONOTHERAPY (NCT02706951); SELECT-EARLY (NCT02706873); SELECT-COMPARE (NCT02629159).

Rheumatoid arthritis (RA) is a disease that causes inflammation of the joints. Doctors have several ways of assessing how bad a patient's disease is, and these often use a combination of signs and symptoms to develop a 'score'. One method is called RAPID3, which is a score based on an overall assessment of the disease by the patient, the level of pain, and the amount of physical disability. An advantage of RAPID3 is that it is quick and easy to use, and since it uses only patient-reported symptoms, it can be measured easily via telemedicine, without the need for an in-person consultation. In this study, we decided to look into the effect of upadacitinib, a drug used for the treatment of RA, on RAPID3 score in patients with RA. We also investigated whether RAPID3 correlates with other ways of measuring RA severity, including scores that use physician-measured factors such as number of affected joints, as this can help show whether RAPID3 is a valid and useful tool. We found that upadacitinib led to long-term improvements in RAPID3 score, and that results were the same in different studies and patient groups, including patients who had not responded well to other treatments. We also found that RAPID3 correlated well with other measures, i.e., improvements in RAPID3 happened in parallel with improvements in other scores. Overall, these results suggest that RAPID3 can be a useful tool in patients with RA.

Evaluation of an IgM/IgG sensitive enzyme immunoassay and the utility of index values for the screening of syphilis infection in a high-risk population.

BACKGROUND: Increasing interest in the use of enzyme immunoassays (EIA) for syphilis screening has generated a considerable need for data on the performance of such tests. METHODS: We compared the performance of 1 EIA, the TREP-SURE EIA to that of the Venereal Disease Research Laboratory (VDRL) and Treponema pallidum particle agglutination assay (TPPA) in the detection of infection with Treponema pallidum. In total, 674 specimens were tested by VDRL and EIA (356 VDRL-nonreactive and 318 VDRL-reactive). All specimens that were found to be reactive by either the VDRL or EIA were subsequently analyzed by TPPA. RESULTS: We found that the TREP-SURE EIA was marginally less sensitive than the VDRL test for screening, but was significantly more specific. All EIA-TPPA discordant specimens were analyzed by multiple tests, including Immunoglobulin M- and G-specific Western blots and an IgM-specific EIA. Signal-to-cutoff ratios (index values) generated by the TREP-SURE EIA were also investigated. It was found that these values may be instructive regarding the interpretation of test results, as they were found to correlate strongly with the probability of positivity on a TPPA assay. Specimens that reacted positively on the EIA with very high index values were found overwhelmingly to be reactive by TPPA, perhaps obviating the need for the testing of most EIA positive specimens with a secondary treponemal test. CONCLUSIONS: An IgM/IgG sensitive EIA would be an effective alternative to VDRL for syphilis screening. Using the EIA index values may provide additional, helpful information to the diagnostic process.

Erosive rheumatoid arthritis in a young patient with mirror hand.

Mirror hand is a congenital anomaly characterised by duplication of the ulnar ray, resulting in polydactyly and functional disability of the hand. It can cause arthralgias and weakness in intrinsic muscles of the hand. We present a young woman who had a surgically corrected mirror hand and subsequently developed aggressive rheumatoid arthritis, which increased her limitations to a significant degree. Early diagnosis and treatment in such cases is very important to prevent long-term disability.

Assessment of rapid tests for detection of human immunodeficiency virus-specific antibodies in recently infected individuals.

We have evaluated four current Food and Drug Administration-cleared rapid tests for human immunodeficiency virus (HIV)-specific antibodies with a panel of specimens from recently infected individuals. Recent infection was detected by RNA-based screening coupled with enzyme immunoassay-based testing. We found that the sensitivities of the various rapid tests vary greatly with regard to their ability to detect HIV-specific antibodies in recently infected individuals.

Hazards posed by a banned drug--phenformin is still hanging around.

The Hospital Authority Toxicology Reference Laboratory confirmed six cases of phenformin use, with or without complications, from July 2005 to November 2006. Two of the patients presented with potentially fatal phenformin-induced lactic acidosis. Phenformin was found (or suspected to be) adulterating Chinese proprietary medicine in five of the six cases. We report these six cases to highlight the underrecognised hazards posed by phenformin, a banned drug in Hong Kong.

Performance of a transcription-mediated-amplification HIV-1 RNA assay in pooled specimens.

BACKGROUND: Very limited data exist on the comparative performance of nucleic acid amplification tests (NATs) for the screening of pooled specimens for acute human immunodeficiency virus (HIV) infection. STUDY DESIGN: In this study, we compared a transcription-mediated-amplification assay (Procleix HIV-1 Discriminatory Assay, [TMA]) with a branched DNA assay (Bayer Versant HIV-1 RNA 3.0 assay, [bDNA]). RESULTS: After re-testing 1552 samples that were negative for HIV RNA by bDNA, we found one additional positive sample with the TMA assay. CONCLUSION: Our results suggest that TMA could potentially detect acute HIV infections missed by other technologies.

The implications of biologic therapy for elective foot and ankle surgery in patients with rheumatoid arthritis.

INTRODUCTION: Rheumatoid arthritis (RA) is one of a number of inflammatory arthropathies resulting in foot pain and deformity. Patients with this disease may require surgical intervention as part of their management. Many of these patients are now taking biologic agents which pose several risks to patients in the perioperative phase. The surgical team therefore need to be aware of these associated complications and how to manage these cases. AIM: This paper aims to review the current literature about perioperative needs (foot and ankle surgery) associated with patients with rheumatoid arthritis receiving biologic therapy. MAIN FINDINGS: The majority of the literature discusses the perioperative complications associated with patients on anti-TNFα therapy with few studies investigating the other biologics in common use. There is conflicting evidence as to the safety of continuing or stopping biologic drug therapy prior to orthopaedic procedures. The British Society for Rheumatology (BSR) have produced guidelines for the management of patients on anti-TNFα therapy or the biologic agent Tocilizumab. These recommendations suggest the risks of post-operative infection need to be balanced against the risk of a post-operative disease flare. In essence, it is suggested anti-TNFα therapy is stopped 3-5 times the half-life of the drug whilst Tocilizumab is stopped 4 weeks prior to surgery. CONCLUSION: Good communication is needed between the surgical team and the local Rheumatology department managing the patient's disease in order to optimise perioperative care. Local pathways may vary from the BSR recommendations to determine the most suitable course of action with regards to continuing or stopping biologic therapy prior to foot and ankle surgery.

The effects of buspirone on occupancy of dopamine receptors and the rat gambling task.

BACKGROUND: The dopamine D3 receptor (DRD3) has been proposed as a target for drug development for the treatment of addictive disorders. Recently, the anxiolytic buspirone has been shown to have affinity for DRD3 and DRD4, and interest in repurposing it for addictive disorders has grown. METHODS: Binding of [3H]-(+)-PHNO in the rat cerebellum and striatum was used to measure occupancy by buspirone of DRD3 or DRD2, respectively. Effects of buspirone in the rat gambling task (rGT) and the five-choice serial reaction time task (5-CSRTT) were examined. RESULTS: Buspirone occupied both the DRD2 and DRD3 at high doses and the DRD3, but not the DRD2, in the narrow dose range of 3 mg/kg. At 10 mg/kg, a disruption of performance on rGT was observed. All measures of performance on the rGT, except for perseverations, were affected at 3 mg/kg. On the 5-CSRTT, omissions were increased. Impairments in the rGT were not mimicked by the effects induced by satiation. Further, buspirone did not impair food-maintained responding under a progressive ratio schedule of reinforcement at any dose, suggesting that the effects of buspirone on the rGT cannot be explained by non-selective actions. CONCLUSIONS: Although buspirone had effects on the rGT at the dose that selectively occupied the DRD3, the effects found do not parallel those found in previous studies of the effects of selective DRD3 antagonists on the rGT. Thus, buspirone may impair performance on the rGT through actions at multiple receptor sites.

Routine surveillance for the detection of acute and recent HIV infections and transmission of antiretroviral resistance.

OBJECTIVE: To estimate the rate of acute and recent HIV infections and the prevalence of primary antiretroviral resistance. DESIGN, SETTING, AND SUBJECTS: A consecutive sample of individuals presenting for HIV testing at the San Francisco municipal sexually transmitted diseased (STD) clinic in 2004 (n = 3789). MAIN OUTCOME MEASURES: HIV antibody-positive specimens were screened by BED IgG capture enzyme immunoassay to identify recent infections. HIV antibody-negative specimens were screened by nucleic acid amplification testing (NAAT) to detect acute infections. Newly detected infections were genotyped to detect primary antiretroviral resistance. RESULTS: There were 11 acute and 44 recent HIV infections among the total 136 newly detected cases. NAAT increased case identification by 8.08% over standard antibody testing. Acute HIV infections were associated with having a known HIV-positive partner, and a history of hepatitis B, syphilis, and chlamydia. The prevalence of primary antiretroviral resistance was 13.2%, with drug-resistant mutations detected in 17 of 129 cases genotyped. Mutations conferring resistance to non-nucleoside reverse transcriptase inhibitors (NNRTI) were present in 11 of 17 cases. CONCLUSION: The integration of HIV nucleic acid amplification, recent infection, and antiretroviral resistance testing enhanced HIV/STD surveillance. The high proportion of NNRTI mutations detected suggests they may be more common in source partners or more fit for transmission than other forms of drug-resistant HIV-1. Primary antiretroviral resistance monitoring in STD clinic patients may guide the selection of treatment and post-exposure prophylaxis regimens active against viruses being transmitted in the community, and provide health departments with surveillance data in a sentinel population at risk of HIV transmission.

Real-Time PCR for detection of herpes simplex virus without nucleic acid extraction.

BACKGROUND: The speed and sensitivity of real-time polymerase chain reaction (PCR) have made it a popular method for the detection of microbiological agents in both research and clinical specimens. For the detection and genotyping of herpes simplex virus (HSV) in clinical specimens, real-time PCR has proven to be faster, more sensitive and safer than earlier methods which included isolation of the virus in cell culture followed by immunofluorescence microscopy. While PCR-based assays for HSV detection posses clear advantages over these earlier techniques, certain aspects of the PCR method remain onerous. The process of extraction and purification of nucleic acid from clinical specimens prior to PCR is particularly cumbersome. Nucleic acid extraction is expensive, time-consuming and provides a step whereby specimens can become contaminated prior to their analysis. Herein, we investigate the necessity of nucleic acid extraction from swab-based clinical specimens for HSV detection by real-time PCR. We find that nucleic acid extraction is unnecessary for specific and sensitive detection of HSV in clinical specimens using real-time PCR. METHODS: Prospective (n = 36) and retrospective (n = 21) clinical specimens from various anatomical sites were analyzed for the presence of herpes simplex virus 1 or 2 by real-time PCR using the RealArt HSV 1/2 LC PCR Kit. Specimens were analyzed by PCR both before and following automated nucleic acid extraction. PCR using extracted and unextracted specimens was also compared to cell culture as a means of detecting HSV. RESULTS: Detection of HSV 1/2 DNA in clinical specimens by real-time PCR did not require that the specimen be subjected to nucleic acid extraction/purification prior to analysis. Each specimen that was detectable by real-time PCR when analyzed in the extracted form was also detectable when analyzed in the unextracted form using the methods herein. The limit of detection of HSV-1 and HSV-2 particles when analyzed in the unextracted form was found to be approximately 17 and 32 virus particles respectively, compared to a sensitivity of 10 copies, for analysis of purified DNA. Omission of the nucleic acid extraction step shortened both the assay time and cost. CONCLUSION: Omission of the nucleic acid extraction step prior to real-time PCR for detection of herpes simplex virus resulted in a more rapid and cost-effective assay, with little impact upon the sensitivity of detection.

Feasibility, acceptability, and cost of tuberculosis testing by whole-blood interferon-gamma assay.

BACKGROUND: The whole-blood interferon-gamma release assay (IGRA) is recommended in some settings as an alternative to the tuberculin skin test (TST). Outcomes from field implementation of the IGRA for routine tuberculosis (TB) testing have not been reported. We evaluated feasibility, acceptability, and costs after 1.5 years of IGRA use in San Francisco under routine program conditions. METHODS: Patients seen at six community clinics serving homeless, immigrant, or injection-drug user (IDU) populations were routinely offered IGRA (Quantiferon-TB). Per guidelines, we excluded patients who were <17 years old, HIV-infected, immunocompromised, or pregnant. We reviewed medical records for IGRA results and completion of medical evaluation for TB, and at two clinics reviewed TB screening logs for instances of IGRA refusal or phlebotomy failure. RESULTS: Between November 1, 2003 and February 28, 2005, 4143 persons were evaluated by IGRA. 225(5%) specimens were not tested, and 89 (2%) were IGRA-indeterminate. Positive or negative IGRA results were available for 3829 (92%). Of 819 patients with positive IGRA results, 524 (64%) completed diagnostic evaluation within 30 days of their IGRA test date. Among 503 patients eligible for IGRA testing at two clinics, phlebotomy was refused by 33 (7%) and failed in 40 (8%). Including phlebotomy, laboratory, and personnel costs, IGRA use cost $33.67 per patient tested. CONCLUSION: IGRA implementation in a routine TB control program setting was feasible and acceptable among homeless, IDU, and immigrant patients in San Francisco, with results more frequently available than the historically described performance of TST. Laboratory-based diagnosis and surveillance for M. tuberculosis infection is now possible.

Electromyographic and laboratory findings in acute Solanum torvum poisoning.

CONTEXT: Solanum torvum berries, known as susumber or turkey berries, are prepared as part of traditional Jamaican dishes usually served with cod and rice. Poisoning is rare. Although toxic compounds have never been definitively isolated, previous reports suggest toxicity results from inhibition of acetylcholinesterases. We present a case of susumber berry poisoning with detailed electromyographic studies and laboratory analysis. CASE DETAILS: A 54-year-old woman presented to the Emergency Department (ED) complaining of vision, speech, and gait changes; emesis; and diffuse myalgias following consumption of susumber berries. The physical examination demonstrated an intact, lucid mental status, miosis, opsoclonus, severe dysarthria, dysmetria, mild extremity tenderness and weakness, and inability to ambulate. Her symptom constellation was interpreted as a stroke. DISCUSSION: Electromyography demonstrated a pattern of early full recruitment as well as myotonia during the period of acute toxicity. Additionally, solanaceous compounds, in particular solasonine and solanidine, were identified in leftover berries and the patient's serum. Store-bought commercial berries and subsequent serum samples were free of such toxic compounds. EMG studies, together with a laboratory analysis of berries or serum can assist in the differential diagnosis of stroke, and provide both a prognostic screening and confirmation of suspected glycoside toxicity.

Rhenium(V) and Technetium(V) Oxo Complexes of an N(2)N'S Peptidic Chelator: Evidence of Interconversion between the Syn and Anti Conformations.

Neutral Re(V) and Tc(V) oxo complexes of the peptide dimethylglycyl-L-seryl-L-cysteinylglycinamide (RP294) were prepared and characterized by HPLC, spectroscopic techniques, and X-ray crystallographic analysis. The peptide was prepared as a single peptide chain using solid phase methods and characterized by HPLC and various spectroscopic techniques. The water-soluble Re(V) oxo complex of dimethylglycyl-L-seryl-L-cysteinylglycinamide [ReO(RP294)] was prepared from the reaction of the peptide with either [ReO(2)(en)(2)]Cl or ReOCl(3)(PPh(3))(2) in the presence of base. The complex exists as two isomers, the serine CH(2)OH group being in the syn oranti conformation with respect to the Re-oxo bond. The ratio of the isomers at room temperature is 1:1.1. The isomers were separated by reverse-phase HPLC, but the isolation of each isomer was complicated by their rapid interconversion in aqueous solution at room temperature. The molecular structure of the syn isomer of the Re complex was determined by X-ray crystallography. Crystals of syn-[ReO(RP294)] (C(12)H(20)N(6)O(5)ReS) are orthorhombic, of space group P2(1)2(1)2(1), with a = 6.954(1) Å, b = 8.0472(1) Å, c = 32.9183(4) Å, and Z = 4. The structure was solved by direct methods and was refined by full-matrix least-squares procedures to R = 0.0327 (R(w) = 0.0838) for 10 447 reflections with I > 2sigma(I). The Re metal was coordinated in a distorted square pyramidal geometry with the oxo moiety in the apical position. The peptide coordinated to ReO(3+) via the N(amine) atom of dimethylglycine, the S(thiolate) atom of cysteine, and the two N(amide) atoms of serine and cysteine (an N(2)N'S donor atom set). The Re atom lies approximately 0.74 Å above the distorted plane formed by the N(2)N'S donor atom set. Variable-pH (1)H NMR spectral data showed the Re complex was stable from pH 5 to 8.5. The reaction of (99)TcO(4)(-) with SnCl(2), sodium gluconate, and RP294 produced the (99)Tc(V) oxo RP294 complex, [(99)TcO(RP294)]. Like the [ReO(RP294)] complex, [(99)TcO(RP294)] also exists in the syn and anti conformations in a ratio of approximately 1:1. The (99m)Tc complex of RP294 was prepared at the tracer level from the reaction of Na[(99m)TcO(4)] with excess SnCl(2), sodium gluconate, and RP294. The (99m)Tc and Re RP294 complexes behaved similarly under identical HPLC conditions.

Design and numerical evaluation of a volume coil array for parallel MR imaging at ultrahigh fields.

In this work, we propose and investigate a volume coil array design method using different types of birdcage coils for MR imaging. Unlike the conventional radiofrequency (RF) coil arrays of which the array elements are surface coils, the proposed volume coil array consists of a set of independent volume coils including a conventional birdcage coil, a transverse birdcage coil, and a helix birdcage coil. The magnetic fluxes of these three birdcage coils are intrinsically cancelled, yielding a highly decoupled volume coil array. In contrast to conventional non-array type volume coils, the volume coil array would be beneficial in improving MR signal-to-noise ratio (SNR) and also gain the capability of implementing parallel imaging. The volume coil array is evaluated at the ultrahigh field of 7T using FDTD numerical simulations, and the g-factor map at different acceleration rates was also calculated to investigate its parallel imaging performance.