A contact binary satellite of the asteroid (152830) Dinkinesh.

Asteroids with diameters less than about 5 km have complex histories because they are small enough for radiative torques (that is, YORP, short for the Yarkovsky-O'Keefe-Radzievskii-Paddack effect)1 to be a notable factor in their evolution2. (152830) Dinkinesh is a small asteroid orbiting the Sun near the inner edge of the main asteroid belt with a heliocentric semimajor axis of 2.19 AU; its S-type spectrum3,4 is typical of bodies in this part of the main belt5. Here we report observations by the Lucy spacecraft6,7 as it passed within 431 km of Dinkinesh. Lucy revealed Dinkinesh, which has an effective diameter of only 720 m, to be unexpectedly complex. Of particular note is the presence of a prominent longitudinal trough overlain by a substantial equatorial ridge and the discovery of the first confirmed contact binary satellite, now named (152830) Dinkinesh I Selam. Selam consists of two near-equal-sized lobes with diameters of 210 m and 230 m. It orbits Dinkinesh at a distance of 3.1 km with an orbital period of about 52.7 h and is tidally locked. The dynamical state, angular momentum and geomorphologic observations of the system lead us to infer that the ridge and trough of Dinkinesh are probably the result of mass failure resulting from spin-up by YORP followed by the partial reaccretion of the shed material. Selam probably accreted from material shed by this event.

Balanced Nonopioid General Anesthesia With Lidocaine Is Associated With Lower Postoperative Complications Compared With Balanced Opioid General Anesthesia With Sufentanil for Cardiac Surgery With Cardiopulmonary Bypass: A Propensity Matched Cohort Study.

BACKGROUND: There are no data on the effect of balanced nonopioid general anesthesia with lidocaine in cardiac surgery with cardiopulmonary bypass. The main study objective was to evaluate the association between nonopioid general balanced anesthesia and the postoperative complications in relation to opioid side effects. METHODS: Patients undergoing cardiac surgery with cardiopulmonary bypass between 2019 and 2021 were identified. After exclusion of patients for heart transplantation, left ventricular assistance device, and off-pump surgery, we classified patients according to an opioid general balanced anesthesia or a nonopioid balanced anesthesia with lidocaine. The primary outcome was a collapsed composite of postoperative complications that comprise respiratory failure and confusion, whereas secondary outcomes were acute renal injury, pneumoniae, death, intensive care unit (ICU), and hospital length of stay. RESULTS: We identified 859 patients exposed to opioid-balanced general anesthesia with lidocaine and 913 patients exposed to nonopioid-balanced general anesthesia. Propensity score matching yielded 772 individuals in each group with balanced baseline covariates. Two hundred thirty-six patients (30.5%) of the nonopioid-balanced general anesthesia versus 186 patients (24.1%) presented postoperative composite complications. The balanced lidocaine nonopioid general anesthesia group was associated with a lower proportion with the postoperative complication composite outcome OR, 0.72 (95% CI, 0.58-0.92; P = .027). The number of patients with acute renal injury, death, and hospital length of stay did not differ between the 2 groups. CONCLUSIONS: A balanced nonopioid general anesthesia protocol with lidocaine was associated with lower odds of postoperative complication composite outcome based on respiratory failure and confusion.

Reproductive tract size and position score: Estimation of genetic parameters for a novel fertility trait in dairy cows.

The dairy industry is moving toward selecting animals with better fertility to decrease the economic losses linked to reproductive issues. The reproductive tract size and position score (SPS) was recently developed in physiological studies as an indicator of pregnancy rate and the number of services to conception. Cows are scored as SPS 1, 2, or 3 based on the size of their reproductive tract and its position in the pelvis, as determined by transrectal palpation. The objective of this study was to estimate genetic parameters for SPS to assess its potential as a novel fertility trait. Phenotypes were collected at the University of British Columbia's research herd from 2017 to 2020, consisting of 3,247 within- and across-lactation SPS records from 490 Holstein cows. A univariate animal model was used to estimate the variance components for SPS. Both threshold and linear models were fit under a Bayesian approach and the results were compared using the Spearman rank correlation (r) between the estimated breeding values. The 2 models ranked the animals very similarly (r = 0.99), and the linear model was selected for further analysis. Genetic correlations with other currently evaluated traits were estimated using a bivariate animal model. The posterior means (± posterior standard deviation) for heritability and repeatability within- and across-lactation were 0.113 (± 0.013), 0.242 (± 0.012), and 0.134 (± 0.014), respectively. The SPS showed null correlations with production traits and favorable correlations with traditional fertility traits, varying from -0.730 (nonreturn rate) to 0.931 (number of services). Although preliminary, these results are encouraging because SPS seems to be more heritable than and strongly genetically correlated with number of services, nonreturn rate, and first service to conception, indicating potential for effective indirect selection response on these traits from SPS genetic selection. Therefore, further studies with larger data sets to validate these findings are warranted.

Agreement between different non-invasive methods of ventricular elastance assessment for the monitoring of ventricular-arterial coupling in intensive care.

Ventricular-arterial coupling is calculated as the arterial elastance to end systolic elastance ratio (EA/Ees). Although the gold standard is invasive pressure volume loop analysis, Chen method is the clinical reference non-invasive method for estimating end systolic elastance (Ees). Several simplified methods calculate Ees from the end systolic pressure to volume ratio (ESP/ESV). The objective of the present study was to determine whether ESP/ESV simplification can be used instead of the Chen formula to measure ventricular-arterial coupling and to monitor changes following therapeutic intervention. In this retrospective, single-center study, 3 non-invasive EA/Ees calculation methods were applied to 86 cardiac ICU patients. The Chen method was used as the reference method. Ees was also calculated according to method 1: Ees1 = 0.9 × SAP/ESV and method 2: Ees2= EA/(1/LVEF) - 1. EA was estimated as 0.9 × SAP/SV (mmHg ml-1). After simplification: EA/Ees1 = EA/Ees2 = (1/LVEF) - 1, with the stroke volume estimated as the product of the aortic velocity-time integral (VTIAo) and the aortic area or as the difference between the end diastolic volume (EDV) and the ESV. All patients received fluid infusion, norepinephrine, or dobutamine. At baseline, the concordance correlation coefficient with EA/EesChen was 0.13 [- 0.07; 0.31] for EA/Ees1 and 0.32 [0.19; 0.44] for EA/Ees2. Bias and limit of agreement were 0.28 [- 0.02; 0.36] and [- 5.8; 2.6] for EA/Ees1 and of 0.44 [0.31; 0.53] and [- 3.2; 2.6] for EA/Ees2. When used to follow variations in EA/Ees following therapeutic interventions, only 65% (for EA/Ees1) and 70% (for EA/Ees2) of measures followed the same trend as EA/EesChen. Our results do not support the use of ESP/ESV based method as substitute for Chen method to measure and assess changes in ventriculo-arterial coupling (EA/Ees) in cardiac intensive care patients. Further investigations are needed to establish the most reliable non-invasive method.

Complications in patients with intramedullary nails: a case series from a single Cambodian surgical clinic.

PURPOSE: Since its development in 1999, the SIGN nail has been used in over 190,000 surgeries spanning 55 countries. To date, however, evaluation of SIGN nail outcomes has been limited to small prospective studies or large retrospective studies using SIGN's online database. This study uses the experience of a single, independent Cambodian surgical clinic to characterize common complications, provide commentary on ways to reduce the risk of those complications, and determine whether several observed nail fractures were due to metallurgic defects. METHODS: Clinic medical records were queried to identify complications in patients with SIGN nails. Data was abstracted including age, sex, mechanism of injury, and latency between injury, primary implantation, and presentation with a complication. Two nails that fractured in vivo were analyzed by light microscopy, scanning electron microscopy, and polarized light microscopy after chemical etching. RESULTS: Fifty-four complications in 51 patients were identified. The most common complications were non-union (n = 26, 48%), infection (n = 16, 30%), flexion limitation (n = 11, 20%), nail fracture (n = 4, 7%), delayed union (n = 4, 7%), and malunion (n = 4, 7%). Other complications included broken or floating screws. Fractography revealed that two of the fractured nails most likely failed by fatigue followed by fast fracture at the site of non-union. We found no evidence of intrinsic nail defects. We identified multiple inconsistencies between SIGN's database and independent clinic records. CONCLUSIONS: Non-union and infection were common relative to all complications. Based on radiographic review, risk for non-union and malunion can be minimized by selecting an appropriate nail diameter, using multiple interlocking screws, and employing the correct implant and approach for fracture morphology when using SIGN nails. Nail fractures were unlikely to be caused by metallurgical flaws. Further study is necessary to determine the appropriate management of non-unions based on radiographic and clinical factors.

The ABC transporter Rv1272c of Mycobacterium tuberculosis enhances the import of long-chain fatty acids in Escherichia coli.

Mycobacterium tuberculosis (Mtb), which causes tuberculosis, is capable of accumulating triacylglycerol (TAG) by utilizing fatty acids from host cells. ATP-binding cassette (ABC) transporters are involved in transport processes in all organisms. Among the classical ABC transporters in Mtb none have been implicated in fatty acid import. Since the transport of fatty acids from the host cell is important for dormancy-associated TAG synthesis in the pathogen, mycobacterial ABC transporter(s) could potentially be involved in this process. Based on sequence identities with a bacterial ABC transporter that mediates fatty acid import for TAG synthesis, we identified Rv1272c, a hitherto uncharacterized ABC-transporter in Mtb that also shows sequence identities with a plant ABC transporter involved in fatty acid transport. We expressed Rv1272c in E. coli and show that it enhances the import of radiolabeled fatty acids. We also show that Rv1272c causes a significant increase in the metabolic incorporation of radiolabeled long-chain fatty acids into cardiolipin, a tetra-acylated phospholipid, and phosphatidylglycerol in E. coli. This is the first report on the function of Rv1272c showing that it displays a long-chain fatty acid transport function.

Assessment of Corrosion, Fretting, and Material Loss of Retrieved Modular Total Knee Arthroplasties.

BACKGROUND: Modular junctions in total hip arthroplasties have been associated with fretting, corrosion, and debris release. The purpose of this study is to analyze damage severity in total knee arthroplasties of a single design by qualitative visual assessment and quantitative material loss measurements to evaluate implant performance and patient impact via material loss. METHODS: Twenty-two modular knee retrievals of the same manufacturer were identified from an institutional review board-approved database. Junction designs included tapers with an axial screw and tapers with a radial screw. Constructs consisted of 2 metal alloys: CoCr and Ti6Al4V. Components were qualitatively scored and quantitatively measured for corrosion and fretting. Negative values represent adhered material. Statistical differences were analyzed using sign tests. Correlations were tested with a Spearman rank order test (P < .05). RESULTS: The median volumetric material loss and the maximum linear depth for the total population were -0.23 mm3 and 5.84 µm, respectively. CoCr components in mixed metal junctions had higher maximum linear depth (P = .007) than corresponding Ti components. Fretting scores of Ti6Al4V alloy components in mixed metal junctions were statistically higher than the remaining groups. Taper angle did not correlate with material loss. CONCLUSION: Results suggest that CoCr components in mixed metal junctions are more vulnerable to corrosion than other components, suggesting preferential corrosion when interfacing with Ti6Al4V. Overall, although corrosion was noted in this series, material loss was low, and none were revised for clinical metal-related reaction. This suggests the clinical impact from corrosion in total knee arthroplasty is low.

Fatigue failure of reverse shoulder humeral tray components of a single design.

BACKGROUND: Modularity in shoulder arthroplasty provides surgical flexibility and facilitates less-complex revision surgery. Modular designs must fit in the glenohumeral joint space, necessitating minimal thickness and careful material selection. The potential for fatigue fracture is higher, and fatigue fracture has been experienced by patients. The purpose of this study was to determine the impact of geometry and materials used for modular humeral trays from a single manufacturer. METHODS: We consecutively retrieved 8 humeral trays of nearly identical designs: 4 Ti-6Al-4V (Ti) and 4 CoCrMo (CoCr). Optical microscopy and scanning electron microscopy were used, along with metallurgical techniques. Finite element and fatigue analyses of the stresses at the humeral tray taper informed observation interpretation. RESULTS: Two Ti devices were revised for in vivo fracture. Scanning electron microscopy showed cracking in the other 2 Ti trays and no evidence of cracking in the CoCr components. A geometric difference in the CoCr devices resulted in a 25% decreased stress under simulated activities of daily living. Accounting for the tray material properties, the fatigue failure envelope ranged from 1000 to 1 million cycles for Ti and from 30,000 to >10 million cycles for CoCr. CONCLUSIONS: All Ti humeral tray retrievals fractured in vivo or were cracked at the taper fillet. No CoCr retrievals showed signs of cracking. Finite element and fatigue analyses predict a 10-fold lifetime increase for the CoCr devices compared with the Ti devices. This study shows that fatigue failure is possible for some reverse shoulder components and is likely exacerbated by fillet radius, tray thickness, and material choice.

Analysis of severely fractured glenoid components: clinical consequences of biomechanics, design, and materials selection on implant performance.

BACKGROUND: The longevity of total shoulder replacement is primarily limited by the performance of the ultrahigh-molecular-weight polyethylene (UHMWPE) glenoid component in vivo. Variations in glenoid design (conformity, thickness), biomechanics (joint kinematics), and UHMWPE material selection (sterilization, cross-linking) distinguish total shoulder replacements from hip and knee arthroplasty devices. These variables can lead to severe mechanical failures, including gross fracture. METHODS: Sixteen retrieved glenoids with severe fracture were analyzed. The explant cohort included 3 material groups (gamma-sterilized Hylamer; gamma-sterilized UHMWPE; and gas plasma-sterilized, remelted, highly cross-linked UHMWPE [HXL]) and a range of conformities (0- to 10-mm radial mismatch). Analysis included fractography (optical and scanning electron microscopy) and Fourier transform infrared spectroscopy for oxidative analysis. RESULTS: Fracture primarily occurred along the exterior rim for all 16 explants. Fourier transform infrared analysis and fractography revealed significant oxidative embrittlement for all gamma-sterilized glenoids. Fatigue striations and internal flaws were evident on the fracture surface of the HXL glenoid, with little oxidation detected. CONCLUSIONS: Fracture initiated at the external rim of all devices. Elevated oxidation levels and visible material distortion for representative gamma-sterilized conventional and Hylamer devices suggest oxidative embrittlement as a driving force for crack inception and subsequent fracture. Brittle fracture of theHXL glenoid resulted from a combination of elevated contact stress due to a nonconforming surface, an internal flaw, and reduced resistance to fatigue crack growth. This demonstrates that glenoid fracture associated with oxidation has not been eliminated with the advent of modern materials (HXL) in the shoulder domain. LEVEL OF EVIDENCE: Basic Science Study; Implant Retrieval Study.

Lenalidomide is safe and active in Waldenström macroglobulinemia.

Lenalidomide is manageable and effective in multiple myeloma, particularly in elderly patients. Surprisingly, the combination of lenalidomide with rituximab produced clinically significant anemia at 25 mg/day for 21/28 days, the highest possible dose, in Waldenström's Macroglobulinemia (WM). We aimed to determine the maximum tolerated dose (MTD) of single agent lenalidomide and determine its impact on WM. RV-WM-0426 is a multicenter dose escalation open label phase 1/2 study of lenalidomide in relapsed/refractory WM (RRWM). Lenalidomide was given orally 21/28 days per cycle for 1 year, at escalated dose of 15 to 20 mg during phase 1 to determine the MTD; the phase 2 part was conducted at the MTD. Seventeen RRWM patients were included. The MTD was established at 15 mg/day 21/28. By ITT analysis, the overall response rate was 29%. With a median follow-up of 36 months, median TTP was 16 months (95% CI 5.5-26), the 5-year OS was 91%. The most frequent adverse events ≥ grade 3 at 15 mg were 14% anemia and 43% neutropenia. The MTD of lenalidomide is 15 mg/day 21/28 days in RRWM. Lenalidomide is active in the treatment of RRWM and the safety profile appears manageable. Future studies may look into combinations of lenalidomide and continuous dosing.

Estrogenic control of reward prediction errors and reinforcement learning.

Gonadal hormones act throughout the brain 1 , and nearly all neuropsychiatric disorders vary in symptom severity with hormonal fluctuations over the reproductive cycle, gestation, and perimenopause 2-4 . Yet the mechanisms by which hormones influence mental and cognitive processes are unclear. Exogenous estrogenic hormones modulate dopamine signaling in the nucleus accumbens core (NAcc) 5,6 , which instantiates reward prediction errors (RPEs) for reinforcement learning 7-16 . Here we show that endogenous estrogenic hormones enhance RPEs and sensitivity to previous rewards by regulating expression of dopamine reuptake proteins in the NAcc. We trained rats to perform a temporal wagering task with different reward states; rats adjusted how quickly they initiated trials across states, balancing effort against expected rewards. Dopamine release in the NAcc reflected RPEs that predicted and causally in-fluenced subsequent initiation times. When fertile, females more quickly adjusted their initiation times to match reward states due to enhanced dopaminergic RPEs in the NAcc. Proteomics revealed reduced expression of dopamine transporters in fertile stages of the reproductive cycle. Finally, genetic suppression of midbrain estrogen receptors eliminated hormonal modulation of behavior. Estrogenic hormones therefore control the rate of reinforcement learning by regulating RPEs via dopamine reuptake, providing a mechanism by which hormones influence neural dynamics for motivation and learning.

Differential deployment of paralogous Wnt genes in the mouse and chick embryo during development.

Genes encoding Wnt ligands are crucial in body patterning and are highly conserved among metazoans. Given their conservation at the protein-coding level, it is likely that changes in where and when these genes are active are important in generating evolutionary variations. However, we lack detailed knowledge about how their deployment has diverged. Here, we focus on four Wnt subfamilies (Wnt2, Wnt5, Wnt7, and Wnt8) in mammalian and avian species, consisting of a paralogous gene pair in each, believed to have duplicated in the last common ancestor of vertebrates. We use three-dimensional imaging to capture expression patterns in detail and carry out systematic comparisons. We find evidence of greater divergence between these subgroup paralogues than the respective orthologues, consistent with some level of subfunctionalization/neofunctionalization in the common vertebrate ancestor that has been conserved. However, there were exceptions; in the case of chick Wnt2b, individual sites were shared with both mouse Wnt2 and Wnt2b. We also find greater divergence, between paralogues and orthologues, in some subfamilies (Wnt2 and Wnt8) compared to others (Wnt5 and Wnt7) with the more highly similar expression patterns showing more extensive expression in more structures in the embryo. Wnt8 genes were most restricted and most divergent. Major sites of expression for all subfamilies include CNS, limbs, and facial region, and in general there were more similarities in gene deployment in these territories with divergent patterns featuring more in organs such as heart and gut. A detailed comparison of gene expression patterns in the limb showed similarities in overall combined domains across species with notable differences that may relate to lineage-specific morphogenesis.

Rational development and evaluation of novel formulations for urinary health.

OBJECTIVE: Urinary tract infections (UTI) among women form a substantial part of medical practice and both patients and medical professionals have an interest in non-antibiotic treatments and preventative measures. This research provides preliminary data on a multi-functional composition, DAPAD, which explored several biologic activities of relevance to UTI. STUDY DESIGN: This formulation included D-mannose, citric acid, three prebiotic compounds, and extracts of dandelion and astragalus. Studies performed employed 4 bacterial strains that have relevance to UTI including E. coli, Proteus mirabilis, Streptococcus agalactiae and Enterococcus faecalis. RESULTS: Key findings from in vitro studies included: DAPAD at full- and half-strength inhibited growth of all UTI bacteria. Evidence for D-mannose agglutination of E. coli was demonstrated. D-mannose also showed unexpected effects on bacterial membrane integrity with vital staining and modest growth restriction. We did not demonstrate growth inhibition by dandelion or astragalus extracts but the latter showed diminished cytokine elaboration by bladder epithelial cells. CONCLUSION: DAPAD is a multifunctional composition that may warrant further development as a UTI treatment or preventive if supported by clinical evaluation.

Unravelling the genetics of non-random fertilization associated with gametic incompatibility.

In the dairy industry, mate allocation is dependent on the producer's breeding goals and the parents' breeding values. The probability of pregnancy differs among sire-dam combinations, and the compatibility of a pair may vary due to the combination of gametic haplotypes. Under the hypothesis that incomplete incompatibility would reduce the odds of fertilization, and complete incompatibility would lead to a non-fertilizing or lethal combination, deviation from Mendelian inheritance expectations would be observed for incompatible pairs. By adding an interaction to a transmission ratio distortion (TRD) model, which detects departure from the Mendelian expectations, genomic regions linked to gametic incompatibility can be identified. This study aimed to determine the genetic background of gametic incompatibility in Holstein cattle. A total of 283,817 genotyped Holstein trios were used in a TRD analysis, resulting in 422 significant regions, which contained 2075 positional genes further investigated for network, overrepresentation, and guilt-by-association analyses. The identified biological pathways were associated with immunology and cellular communication and a total of 16 functional candidate genes were identified. Further investigation of gametic incompatibility will provide opportunities to improve mate allocation for the dairy cattle industry.

Vasopressor-Sparing Strategies in Patients with Shock: A Scoping-Review and an Evidence-Based Strategy Proposition.

Despite the abundant literature on vasopressor therapy, few studies have focused on vasopressor-sparing strategies in patients with shock. We performed a scoping-review of the published studies evaluating vasopressor-sparing strategies by analyzing the results from randomized controlled trials conducted in patients with shock, with a focus on vasopressor doses and/or duration reduction. We analyzed 143 studies, mainly performed in septic shock. Our analysis demonstrated that several pharmacological and non-pharmacological strategies are associated with a decrease in the duration of vasopressor therapy. These strategies are as follows: implementing a weaning strategy, vasopressin use, systemic glucocorticoid administration, beta-blockers, and normothermia. On the contrary, early goal directed therapies, including fluid therapy, oral vasopressors, vitamin C, and renal replacement therapy, are not associated with an increase in vasopressor-free days. Based on these results, we proposed an evidence-based vasopressor management strategy.

Human breath analysis: methods for sample collection and reduction of localized background effects.

Solid-phase microextraction (SPME) was applied, in conjunction with gas chromatography-mass spectrometry, to the analysis of volatile organic compounds (VOCs) in human breath samples without requiring exhaled breath condensate collection. A new procedure, exhaled breath vapor (EBV) collection, involving the active sampling and preconcentration of a breath sample with a SPME fiber fitted inside a modified commercial breath-collection device, the RTube, is described. Immediately after sample collection, compounds are desorbed from the SPME fiber at 250 degrees C in the GC-MS injector. Experiments were performed using EBV collected at -80 degrees C and at room temperature, and the results compared to the traditional method of collecting exhaled breath condensate at -80 degrees C followed by passive SPME sampling of the collected condensate. Methods are compared in terms of portability, ease-of-use, speed of analysis, and detection limits. The need for a clean air supply for the study subjects is demonstrated using several localized sources of VOC contaminants including nail polish, lemonade, and gasoline. Various simple methods to supply clean inhaled air to a subject are presented. Chemical exposures are used to demonstrate the importance of providing cleaned air (organic vapor respirator) or an external air source (tubing stretched to a separate room). These techniques allow for facile data interpretation by minimizing background contaminants. It is demonstrated herein that this active SPME breath-sampling device provides advantages in the forms of faster sample collection and data analysis, apparatus portability and avoidance of power or cooling requirements, and performance for sample collection in a contaminated environment.

Pupillometry pain index decreases intraoperative sufentanyl administration in cardiac surgery: a prospective randomized study.

Pupillometry has proven effective for the monitoring of intraoperative analgesia in non-cardiac surgery. We performed a prospective randomized study to evaluate the impact of an analgesia-guided pupillometry algorithm on the consumption of sufentanyl during cardiac surgery. Fifty patients were included prior to surgery. General anesthesia was standardized with propofol and target-controlled infusions of sufentanyl. The standard group consisted of sufentanyl target infusion left to the discretion of the anesthesiologist. The intervention group consisted of sufentanyl target infusion based on the pupillary pain index. The primary outcome was the total intraoperative sufentanyl dose. The total dose of sufentanyl was lower in the intervention group than in the control group and (55.8 µg [39.7-95.2] vs 83.9 µg [64.1-107.0], p = 0.04). During the postoperative course, the cumulative doses of morphine (mg) were not significantly different between groups (23 mg [15-53] vs 24 mg [17-46]; p = 0.95). We found no significant differences in chronic pain at 3 months between the 2 groups (0 (0%) vs 2 (9.5%) p = 0.49). Overall, the algorithm based on the pupillometry pain index decreased the dose of sufentanyl infused during cardiac surgery.Clinical trial number: NCT03864016.

Use of single particle aerosol mass spectrometry for the automated nondestructive identification of drugs in multicomponent samples.

In this work, single particle aerosol mass spectrometry (SPAMS) was used to identify the active drug ingredients in samples of multicomponent over-the-counter (OTC) drug tablets with minimal damage to the tablets. OTC drug tablets in various formulations were analyzed including single active ingredient tablets and multi-ingredient tablets. Using a sampling apparatus developed in-house, micrometer-sized particles were simultaneously dislodged from tablets and introduced to the SPAMS, where dual-polarity mass spectra were obtained from individual particles. Active ingredients were identified from the parent ions and fragment ions formed from each sample, and alarm files were developed for each active ingredient, allowing successful automated identification of each compound in a mixture. The alarm algorithm developed for SPAMS correctly identified all drug compounds in all single-ingredient and multi-ingredient tablets studied. A further study demonstrated the ability of this technique to identify the active ingredient in a single tablet analyzed in the presence of several other nonidentical tablets. In situ measurements were also made by sampling directly from a drug sample in its original bottle. A single tablet embedded in 11 identical tablets of different composition was detected in this manner. Overall, this work demonstrates the ability of the SPAMS technique to detect a target drug compound both in complex tablets, i.e., multidrug ingredient tablets, and complex sampling environments, i.e., multitablet sampling sources. The technique is practically nondestructive, leaving the characteristic shape, color, and imprint of a tablet intact for further analysis. Applications of this technique may include forensic and pharmaceutical analysis.

Reagentless detection of Mycobacteria tuberculosis H37Ra in respiratory effluents in minutes.

Two similar mycobacteria, Mycobacteria tuberculosis H37Ra and Mycobacteria smegmatis are rapidly detected and identified within samples containing a complex background of respiratory effluents using single-particle aerosol mass spectrometry (SPAMS). M. tuberculosis H37Ra (TBa), an avirulent strain, is used as a surrogate for virulent tuberculosis; M. smegmatis (MSm) is utilized as a near-neighbor confounder for TBa. Bovine lung surfactant and human exhaled breath condensate are used as first-order surrogates for infected human lung expirations from patients with pulmonary tuberculosis. This simulated background sputum is mixed with TBa or MSm and nebulized to produce conglomerate aerosol particles, single particles that contain a bacterium embedded within a background respiratory matrix. Mass spectra of single conglomerate particles exhibit ions associated with both respiratory effluents and mycobacteria. Spectral features distinguishing TBa from MSm in pure and conglomerate particles are shown. SPAMS pattern matching alarm algorithms are able to distinguish TBa-containing particles from background matrix and MSm for >50% of the test particles, which is sufficient to enable a high probability of detection and a low false alarm rate if an adequate number of such particles are present. These results indicate the potential usefulness of SPAMS for rapid, reagentless tuberculosis screening.

Autonomous, broad-spectrum detection of hazardous aerosols in seconds.

Actual or surrogate chemical, biological, radiological, nuclear, and explosive materials and illicit drug precursors can be rapidly detected and identified when in aerosol form by a Single-Particle Aerosol Mass Spectrometry (SPAMS) system. This entails not only the sampling of such particles but also the physical analysis and subsequent data analysis leading to a highly reliable alarm state. SPAMS hardware is briefly reviewed. SPAMS software algorithms are discussed in greater detail. A laboratory experiment involving actual threat and surrogate releases mixed with ambient background aerosols demonstrates broad-spectrum detection within seconds. Data from a field test at the San Francisco International Airport demonstrate extended field operation with an ultralow false alarm rate. Together these data sets demonstrate a significant and important advance in rapid aerosol threat detection.