279 results on '"Murray DL"'
Search Results
2. Water Balance of Narrow - Leaved Snow Tussock
- Author
-
Hydrology and Water Resources Symposium (1989 : Christchurch, N.Z.), Campbell, DI, and Murray, DL
- Published
- 1989
3. Chemoprophylaxis for household contacts of index cases of invasive non-type b Haemophilus influenzae disease
- Author
-
Murray Dl and Gilsdorf
- Subjects
Microbiology (medical) ,Adult ,Male ,medicine.medical_specialty ,Index (economics) ,Haemophilus Infections ,Disease ,medicine.disease_cause ,Chemoprevention ,Haemophilus influenzae ,Internal medicine ,medicine ,Disease Transmission, Infectious ,Humans ,Child ,Family Health ,Family Characteristics ,Infection Control ,business.industry ,Infant ,Anti-Bacterial Agents ,Infectious Diseases ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Chemoprophylaxis ,Female ,Rifampin ,business - Published
- 2001
4. Topographic influence on the pattern of flow through Bass Strait
- Author
-
Baines, PG, primary and Murray, DL, additional
- Published
- 1995
- Full Text
- View/download PDF
5. Laboratory persistence and clinical progression of small monoclonal abnormalities.
- Author
-
Murray DL, Seningen JL, Dispenzieri A, Snyder MR, Kyle RA, Rajkumar SV, Katzmann JA, Murray, David L, Seningen, Justin L, Dispenzieri, Angela, Snyder, Melissa R, Kyle, Robert A, Rajkumar, S Vincent, and Katzmann, Jerry A
- Abstract
Monoclonal gammopathy of undetermined significance (MGUS) that presents with no quantifiable M spike on immunofixation electrophoresis (IFE) can be termed IFE MGUS. We retrospectively identified patients with IFE MGUS who were monitored with at least 1 subsequent assessment that included an IFE, and evaluated the persistence of the monoclonal protein and the progression of disease. Although the monoclonal proteins persisted in the majority of patients, 16% did not experience this persistence, and had no documented immunomodulatory therapy. After a median follow-up of 3.9 years, the disease clinically progressed in 14 patients (3.2%). Eight of these 14 patients with clinical progression had an immunoglobulin (Ig) A IFE M protein and 6 had an IgG M protein. This study demonstrates that in some patients with IFE MGUS, the M proteins are transient and that IgA IFE MGUS is more likely to persist and progress to myeloma. [ABSTRACT FROM AUTHOR]
- Published
- 2012
6. Rabies.
- Author
-
Mani CS, Murray DL, Mani, Chitra S, and Murray, Dennis L
- Published
- 2006
- Full Text
- View/download PDF
7. Triage decisions in child care for sick children.
- Author
-
Desguin BW and Murray DL
- Published
- 1990
- Full Text
- View/download PDF
8. Preventing and managing pneumococcal disease.
- Author
-
Murray DL
- Abstract
The new conjugate vaccine is a promising tool for preventing pneumococcal disease in children. Until its benefits are fully realized, however pediatricians need to know the best ways to treat increasingly resistant disease. [ABSTRACT FROM AUTHOR]
- Published
- 2001
9. Varicella infection in adults reporting prior varicella.
- Author
-
Murray DL and Murray, D L
- Published
- 1998
- Full Text
- View/download PDF
10. Recommended childhood immunization schedule.
- Author
-
Halsey NA, Chesney PJ, Gerber MA, Gromisch DS, Kohl S, Marcy SM, Marks MI, Murray DL, Overall JC Jr., Pickering LK, Whitley RJ, Yogev R, and American Academy of Pediatrics. Committee on Infectious Diseases
- Published
- 1996
11. Comparison of 2 Free Light Chain Assays: Performance of the Free Light Chain Ratio as a Risk Factor for MGUS Progression.
- Author
-
Wang Q, Andress BD, Pazdernik VMK, Larson DR, Coker JD, Dasari S, Rajkumar V, Dispenzieri A, Murray DL, and Willrich MAV
- Abstract
Background: New immunoglobulin free light chain (FLC) assays are available. Despite analytical differences, it seems possible to use free light chain ratios (FLCr) generated by different assays and apply similar cut-points for the diagnosis of multiple myeloma. It is still unknown if we can use different assays for risk stratification of patients with monoclonal gammopathy of undetermined significance (MGUS)., Methods: Patients diagnosed with MGUS (N = 923) had FLC tested using a nephelometric FreeLite (Binding Site) assay on BNII instruments (Siemens) and a Sebia FLC assay (Sebia) on a DS2 ELISA analyzer (Dynex). Patients were followed up for progression to any plasma cell dyscrasia (PCD) for several decades. The Mayo MGUS risk stratification model for progression was assessed with both assays (M-spike >1.5 g/dL; non-IgG isotype and abnormal FLCr), using package insert reference intervals (RI) and a new metric called principal component 2 (PC2)., Results: There were 94 events of progression to PCD in the cohort during a median of 38 years of follow-up. Freelite and Sebia FLC showed similar hazard ratios in the risk models for elevated FLCr. An alternative clinical decision point lower than the package insert RI was evaluated for the Sebia assay, which improved risk stratification for patients with a low FLCr. The PC2 metric showed similar performance to the FLCr in models, without superior benefit., Conclusions: The Sebia ELISA-based FLC assay can be employed in an MGUS risk stratification model with similar performance to the original 2005 risk stratification model using the FreeLite assay., (© Association for Diagnostics & Laboratory Medicine 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
- Published
- 2024
- Full Text
- View/download PDF
12. Myeloma Therapy for Monoclonal Gammopathy of Thrombotic Significance.
- Author
-
Salmasi G, Murray DL, and Padmanabhan A
- Subjects
- Humans, Paraproteinemias complications, Thrombosis etiology, Male, Middle Aged, Aged, Female, Multiple Myeloma complications, Multiple Myeloma drug therapy
- Published
- 2024
- Full Text
- View/download PDF
13. Correction: Value of bone marrow examination in determining response to therapy in patients with multiple myeloma in the context of mass spectrometry-based M-protein assessment.
- Author
-
Claveau JS, Murray DL, Dispenzieri A, Kapoor P, Binder M, Buadi F, Dingli D, Fonder A, Gertz M, Gonsalves W, Hayman S, Hobbs M, Hwa YL, Kourelis T, Lacy M, Leung N, Lin Y, Warsame R, Kyle RA, Rajkumar V, and Kumar SK
- Published
- 2024
- Full Text
- View/download PDF
14. In Reply to Serum Free Light Chain and Drift: Calibrator Adjustment Needed?
- Author
-
Murray DL
- Subjects
- Humans, Calibration, Immunoglobulin Light Chains
- Published
- 2024
- Full Text
- View/download PDF
15. Infliximab Therapeutic monitoring by tryptic peptide LC-MS/MS method improvements lead to improved accuracy with decreased imprecision and turnaround time.
- Author
-
Ladwig PM, Rivard AL, Barbeln A, Maus A, Murray DL, Snyder MR, and Willrich MAV
- Abstract
Introduction: Therapeutic drug monitoring of infliximab has become the standard of care for inflammatory bowel disease in the setting of loss of response to therapy, and occasionally in proactive therapy personalization. Measurement of infliximab by tryptic peptide HPLC-MS/MS has been available since 2015, mostly in reference laboratories., Objectives: Here, we present method improvements to our original published method leading to a more efficient, robust, and high throughput tryptic peptide HPLC-MS/MS assay for infliximab quantitation., Methods: Deidentified residual serum samples submitted for clinical testing were used for method comparison and infliximab was spiked into normal human serum for performance studies. Improvements included the addition of a stable isotope labeled full length infliximab internal standard (IS) replacing a surrogate IS, and immunoenrichment using Melon Gel for immunoglobulins replacing the saturated ammonium sulfate precipitation. Digestion and chromatography were optimized, and automation was added. The method improvements were validated to include precision, accuracy, reportable range, linearity, and analytical sensitivity., Results: The digestion time was reduced from overnight to 1 h. The assay analytical measuring range (AMR) remained the same throughout improvements, 1-100 µg/mL, with linearity of 0.98x + 0.50, R
2 = 1.00. Intra- and inter-assay imprecision were less than 5 % CV at four different concentrations. Accuracy was assessed with 106 patients within the AMR; Passing-Bablok Regression yielded a slope of 1.00 and a y-intercept of 0.25. Turnaround time was reduced by 1 day, and imprecision of three levels of quality control trended down after new method implementation., Conclusions: Method improvements including automation have allowed for assay completion in half a day, improving robustness and turnaround time., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mayo Clinic has financial interest related to this research, and patents to the infliximab test have been issued. The remaining authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 THE AUTHORS.)- Published
- 2024
- Full Text
- View/download PDF
16. Clinical specificity of two assays for immunoglobulin kappa and lambda free light chains.
- Author
-
Farnsworth CW, Roemmich B, Spears GM, Murray DL, Dispenzieri A, and Willrich MAV
- Subjects
- Humans, Immunoglobulin kappa-Chains, Immunoglobulin lambda-Chains, Immunoglobulin Light Chains, Paraproteinemias diagnosis, Kidney Diseases
- Abstract
Objectives: Free light chain (FLC) assays and the ratio of κ/λ are recommended for diagnosis, prognosis and monitoring of plasma cell dyscrasias (PCD). Limited data exists on FLC clinical specificity in patients diagnosed with other conditions., Methods: We assessed the κ, λ, and κ/λ FLC ratio using the FreeLite assay and the Sebia FLC ELISA assay in 176 patients with clinical presentations of fatigue, anemia, polyclonal hypergammaglobulinemia, joint disorders, kidney disease and non PCD-cancers with no monoclonal protein observed on serum protein electrophoresis or MASS-FIX immunoglobulin isotyping. Manufacturer defined reference intervals (RI) and glomerular filtration rate (GFR) specific RI (renal RI) were utilized., Results: For the κ/λ ratio, 68.7 % (121/176) of specimens on the FreeLite and 87.5 % (154/176) of specimens on the Sebia assay were within RI. For κ, 68.2 % (120/176) and 72.2 % (127/176) of results were outside RI for FreeLite and Sebia respectively. For λ, 37.5 % (66/176) and 84.1 % (148/176) of FreeLite and Sebia results were outside RI. With FreeLite and Sebia, patients with kidney disease (n=25) had the highest κ/λ ratios. 44 patients (25.0 %) had GFR <60 mL/min/BSA. When renal RI were applied, 13.6 % had a FLCr outside the renal RI with FreeLite, and 4.5 % with Sebia., Conclusions: In a cohort of patients with signs and symptoms suggestive of PCDs, but ultimately diagnosed with other conditions, Sebia FLC had improved clinical specificity relative to FreeLite, if one was using an abnormal κ/λ ratio as a surrogate for monoclonality., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)
- Published
- 2023
- Full Text
- View/download PDF
17. Effects of temperature heterogeneity on freshwater turtle habitat selection at their northern range limit.
- Author
-
Auge AC, Blouin-Demers G, and Murray DL
- Subjects
- Animals, Temperature, Ecosystem, Body Temperature Regulation, Fresh Water, Turtles physiology
- Abstract
Environmental temperature is a crucial resource for ectotherms, affecting their physiology, behaviour and fitness. To maintain body temperatures within a suitable performance range, ectotherms select thermally-favourable locations, but this selection may be challenging in environments with high spatio-temporal heterogeneity. We assessed thermal habitat selection in two freshwater turtles (Emydoidea blandingii; Chrysemys picta) within a thermally heterogeneous environment at two spatial scales (selection of home ranges within the landscape, selection of locations within home ranges) and across seasons, by comparing temperatures at turtle locations vs. those available in the environment. Turtles selected warmer locations compared to those available in aquatic and terrestrial habitats only within home ranges, but did not show any temperature preferences when selecting home ranges at the larger scale. Turtles selected locations that were less thermally-variable than their surroundings, both at the home range scale and within home ranges. Thermal habitat selection was strongest during colder and more thermally-variable pre-nesting season compared to later periods. Despite differences in thermal mass between species, both species responded similarly to temperature variation. We conclude that freshwater turtles at their northern range margin select suitable microclimates within the suite of conditions that are naturally available., Competing Interests: Declaration of competing interest The authors declare there are no conflicts of interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
18. Diversity and composition of mixed-ploidy unisexual salamander assemblages reflect the key influence of host species.
- Author
-
Bare EA, Bogart JP, Wilson C, Murray DL, and Hossie TJ
- Subjects
- Male, Animals, Ambystoma, Biodiversity, Ploidies, Urodela, Semen
- Abstract
Understanding processes that govern and sustain biological diversity is a central goal of community ecology. Unisexual complexes, where reproduction depends on sperm from males of one or more bisexual host species, are rare and the processes driving their diversity and structure remain poorly understood. Unisexual Ambystoma salamanders produce distinct biotypes ('genomotypes') depending on which bisexual species they 'steal' sperm from. This reproductive mode should generate distinct assemblages depending on the locally available bisexual host species. Yet, how availability and relative abundance of multiple bisexual hosts influences composition and diversity of natural unisexual assemblages at local or regional scales remains unknown. We hypothesize that host identity most directly drives local assemblage composition, with host variation associated with increased beta and gamma diversity within unisexuals. We collected genetic samples from Ambystoma salamanders across Pelee Island, Ontario, Canada (2015-2022). Two host species were identified (A. texanum and A. laterale) with nine sites having a single host and one site having both. Unisexual assemblages were grouped into four clusters by similarity, with host identity being a key determinant. Gamma diversity increased as a result of distinct host-specific assemblages forming at different sites on the island (i.e., high beta diversity). Assemblage composition, but not diversity, was correlated with relative host abundance, which may reflect matching niche requirements between host and unisexual forms they produce. Our results demonstrate that diversity and structure of unisexual assemblages are clearly shaped by their host(s) and such systems may serve as models for studying how biotic interactions shape ecological communities., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
- Published
- 2023
- Full Text
- View/download PDF
19. Utilizing Mass Spectrometry to Detect and Isotype Monoclonal Proteins in Urine: Comparison to Electrophoretic Methods.
- Author
-
Moonen DH, Kohlhagen M, Dasari S, Willrich MA, Kourelis T, Dispenzieri A, and Murray DL
- Subjects
- Humans, Immunoglobulin kappa-Chains, Mass Spectrometry, Immunoelectrophoresis methods, Antibodies, Monoclonal, Immunoglobulin Light Chains, Paraproteinemias
- Abstract
Background: Matrix assisted laser desorption ionization time of flight mass spectrometry coupled to immune enrichment (MASS-FIX) as an alternative to serum immunofixation electrophoresis has demonstrated increased sensitivity in monoclonal protein (MP) detection with improved laboratory workflow. This study explored similar replacement of urine immunofixation electrophoresis (u-IFE) with urine MASS-FIX (u-MASS-FIX) by method comparison., Methods: Residual urine (n = 1008) from Mayo Clinic patients with a known plasma cell disease were assayed neat by u-MASS-FIX analysis. Each sample was paired with the following: u-IFE, urine total protein, urine protein electrophoresis, serum κ/λ free light chain (LC) ratio (rFLC), and serum MASS-FIX (s-MASS-FIX). Analytical sensitivities were measured in pooled urine spiked with daratumumab., Results: u-IFE and u-MASS-FIX had 91% agreement in determining the presence/absence of MPs (Cohen kappa = 0.8200). In discrepant cases, serum rFLC statistically aligned more closely with positive u-MASS-FIX cases than u-IFE. Patients positive by both s-MASS-FIX and u-MASS-FIX had matching MP masses (±20 daltons) in 94% of cases. The u-MASS-FIX spectra further identified κ/λ LC fragments and glycosylated LCs not appreciated on u-IFE. The unconcentrated u-MASS-FIX limit of detection of 0.156 mg/mL was determined equivalent to 100× concentrated u-IFE., Conclusion: u-MASS-FIX is a reliable alternative to u-IFE with the added benefits of LC glycosylation detection and MP mass tracking between serum and urine. Furthermore, u-MASS-FIX is performed using neat urine. Eliminating the need to concentrate urine for u-IFE has potential to increase productivity by decreasing labor minutes per test., (© American Association for Clinical Chemistry 2023.)
- Published
- 2023
- Full Text
- View/download PDF
20. Kappa Free Light Chain Drift Prompts the Need for a New Upper Limit of Normal Free Light Chain Ratio to Avoid an Epidemic of Kappa Light Chain Monoclonal Gammopathy of Undermined Significance.
- Author
-
Rozenova K, Willrich M, Snyder M, Dasari S, Kourelis T, Rajkumar SV, Kumar S, Dispenzieri A, and Murray DL
- Subjects
- Humans, Retrospective Studies, Immunoglobulin lambda-Chains, Sensitivity and Specificity, Immunoglobulin Light Chains, Immunoglobulin kappa-Chains, Antibodies, Monoclonal, Paraproteinemias diagnosis, Monoclonal Gammopathy of Undetermined Significance diagnosis
- Abstract
Background: Multiple laboratory tests are employed for detection of monoclonal proteins in patients and include serum protein electrophoresis (SPEP), immunofixation electrophoresis, free light chain (FLC) immunoassay, and mass spectrometry (Mass-Fix). Recently, reports on a drift in FLC quantitation results have been brought to light., Methods: We studied a cohort of 16 887 patients whose sera were tested for a monoclonal protein by a FLC assay, serum protein electrophoresis, and Mass-Fix. This is a retrospective study designed to assess the impact of a drift on the performance of FLC ratio (rFLC) in groups of patients with and without detectable plasma cell disorders (PCDs)., Results: The results demonstrated that 63% of patients with monoclonal protein equal or higher than 2 g/L (by SPEP) had an abnormal rFLC (reference range 0.26-1.65). Conversely, 16% of patients with undetectable monoclonal protein by other methods (i.e., SPEP and Mass-Fix) who also had no record of treated PCD had an abnormal rFLC. In these cases, there was an imbalance in the number of kappa high rFLCs to lambda low rFLCs of 201 to 1., Conclusions: The results of this study suggest decreased specificity of rFLC for a monoclonal kappa FLC in the 1.65 to 3.0 range., (© American Association for Clinical Chemistry 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2023
- Full Text
- View/download PDF
21. When death comes: linking predator-prey activity patterns to timing of mortality to understand predation risk.
- Author
-
Shiratsuru S, Studd EK, Boutin S, Peers MJL, Majchrzak YN, Menzies AK, Derbyshire R, Jung TS, Krebs CJ, Boonstra R, and Murray DL
- Subjects
- Animals, Ecosystem, Predatory Behavior, Hares, Lynx
- Abstract
The assumption that activity and foraging are risky for prey underlies many predator-prey theories and has led to the use of predator-prey activity overlap as a proxy of predation risk. However, the simultaneous measures of prey and predator activity along with timing of predation required to test this assumption have not been available. Here, we used accelerometry data on snowshoe hares ( Lepus americanus ) and Canada lynx ( Lynx canadensis ) to determine activity patterns of prey and predators and match these to precise timing of predation. Surprisingly we found that lynx kills of hares were as likely to occur during the day when hares were inactive as at night when hares were active. We also found that activity rates of hares were not related to the chance of predation at daily and weekly scales, whereas lynx activity rates positively affected the diel pattern of lynx predation on hares and their weekly kill rates of hares. Our findings suggest that predator-prey diel activity overlap may not always be a good proxy of predation risk, and highlight a need for examining the link between predation and spatio-temporal behaviour of predator and prey to improve our understanding of how predator-prey behavioural interactions drive predation risk.
- Published
- 2023
- Full Text
- View/download PDF
22. Mass spectrometry-based assessment of prostate cancer-associated crystalloids reveals enrichment for growth and differentiation factor 15.
- Author
-
Tekin B, Dasari S, Theis JD, Vrana JA, Murray DL, Oglesbee D, Thompson RH, Leibovich BC, Boorjian SA, Whaley RD, Hernandez LH, Jimenez RE, Cheville JC, Karnes RJ, Sukov WR, and Gupta S
- Subjects
- Male, Humans, Chromatography, Liquid, Proteomics, Tandem Mass Spectrometry, Crystalloid Solutions, Prostatic Neoplasms metabolism, Adenocarcinoma pathology
- Abstract
Intraluminal crystalloids are a common finding within malignant prostatic acini and are infrequently identified within benign glands. The proteomic composition of these crystalloids remains poorly understood and may provide insight regarding prostate cancer pathogenesis. Laser microdissection-assisted liquid chromatography-tandem mass spectrometry (LMD-LC-MS/MS) was performed to compare proteomic composition of corpora amylacea within benign acini (n = 9), prostatic adenocarcinoma-associated crystalloids (n = 8), benign (n = 8), and malignant prostatic acini (n = 6). The expression of candidate biomarkers was then measured in urine specimens from patients with (n = 8) and without prostate cancer (n = 10) using ELISA, and immunohistochemistry-based expression in adjacent prostate cancer and benign glands was assessed in 56 whole-slide sections from radical prostatectomy specimens. LMD-LC-MS/MS revealed enrichment for the C-terminal portion of growth and differentiation factor 15 (GDF15) in prostatic crystalloids. Although urinary GDF15 levels were higher in patients with prostatic adenocarcinoma compared to those without (median: 1561.2 versus 1101.3, arbitrary units), this did not meet statistical significance (P = 0.07). Immunohistochemistry for GDF15 revealed occasional positivity in benign glands (median H-score: 30, n = 56), and diffuse positivity in prostatic adenocarcinoma (median H-score: 200, n = 56, P < 0.0001). No significant difference was identified within different prognostic grade groups of prostatic adenocarcinoma, or within malignant glands with large cribriform morphology. Our results show that the C-terminal portion of GDF15 is enriched in prostate cancer-associated crystalloids, and higher GDF15 expression is seen in malignant rather than benign prostatic acini. Improved understanding of the proteomic composition of prostate cancer-associated crystalloids provides the rationale for evaluating GDF15 as a urine-based biomarker of prostate cancer., (Copyright © 2023 Elsevier Inc. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
23. Analysis of monoclonal immunoglobulins from bone marrow plasma cells using immunopurification and LC-MS.
- Author
-
Barnidge DR, Dispenzieri A, Jevremovic D, and Murray DL
- Abstract
Introduction: Clonal plasma cells secrete immunoglobulins, each with the exact same amino acid sequence, that are referred to as monoclonal immunoglobulins. The monoclonal heavy chain and light chain secreted from clonal plasma cells have the same molecular mass prior to the addition of post-translational modifications (PTMs) since their amino acid sequences are the same., Objective: To examine the molecular masses of monoclonal light chains and heavy chains isolated directly from the cytoplasm of bone marrow (BM) plasma cells and compare them to the serum derived monoclonal heavy and light chains., Methods: Using immunopurification and LC-MS we compared the molecular masses of immunoglobulins immunopurified from a patient's serum to those immunopurified from the cytoplasm of their BM plasma cells., Results: Our findings demonstrate that the light chain molecular masses were identical whether they were obtained from serum or plasma cell cytoplasm. However, the heavy chain molecular masses did not match in bone marrow and serum due to differences in glycosylation, a common post-translational modification (PTM) found on the heavy chain., Conclusion: The data presented here show that by using LC-MS to analyze monoclonal immunoglobulins (also referred to as miRAMM) additional phenotype information is obtained at the cellular level which is complementary to other more common techniques such as flow cytometry and histopathology., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 THE AUTHORS.)
- Published
- 2023
- Full Text
- View/download PDF
24. Does coat colour influence survival? A test in a cyclic population of snowshoe hares.
- Author
-
Oli MK, Kenney AJ, Boonstra R, Boutin S, Murray DL, Peers MJL, Gilbert BS, Jung TS, Chaudhary V, Hines JE, and Krebs CJ
- Subjects
- Animals, Color, Ecosystem, Canada, Population Dynamics, Seasons, Hares
- Abstract
Some mammal species inhabiting high-latitude biomes have evolved a seasonal moulting pattern that improves camouflage via white coats in winter and brown coats in summer. In many high-latitude and high-altitude areas, the duration and depth of snow cover has been substantially reduced in the last five decades. This reduction in depth and duration of snow cover may create a mismatch between coat colour and colour of the background environment, and potentially reduce the survival rate of species that depend on crypsis. We used long-term (1977-2020) field data and capture-mark-recapture models to test the hypothesis that whiteness of the coat influences winter apparent survival in a cyclic population of snowshoe hares ( Lepus americanus ) at Kluane, Yukon, Canada. Whiteness of the snowshoe hare coat in autumn declined during this study, and snowshoe hares with a greater proportion of whiteness in their coats in autumn survived better during winter. However, whiteness of the coat in spring did not affect subsequent summer survival. These results are consistent with the hypothesis that the timing of coat colour change in autumn can reduce overwinter survival. Because declines in cyclic snowshoe hare populations are strongly affected by low winter survival, the timing of coat colour change may adversely affect snowshoe hare population dynamics as climate change continues.
- Published
- 2023
- Full Text
- View/download PDF
25. Value of bone marrow examination in determining response to therapy in patients with multiple myeloma in the context of mass spectrometry-based M-protein assessment.
- Author
-
Claveau JS, Murray DL, Dispenzieri A, Kapoor P, Binder M, Buadi F, Dingli D, Fonder A, Gertz M, Gonsalves W, Hayman S, Hobbs M, Hwa YL, Kourelis T, Lacy M, Leung N, Lin Y, Warsame R, Kyle RA, Rajkumar V, and Kumar SK
- Subjects
- Humans, Bone Marrow Examination, Bone Marrow, Mass Spectrometry, Multiple Myeloma diagnosis, Multiple Myeloma drug therapy
- Published
- 2023
- Full Text
- View/download PDF
26. Family Connects: A Novel Social Needs Program Within a Pediatric Emergency Department.
- Author
-
VonHoltz LA, Murray AL, and Cullen DL
- Subjects
- Child, Humans, Emergency Service, Hospital, Family
- Published
- 2023
- Full Text
- View/download PDF
27. Behavioural adjustments of predators and prey to wind speed in the boreal forest.
- Author
-
Studd EK, Peers MJL, Menzies AK, Derbyshire R, Majchrzak YN, Seguin JL, Murray DL, Dantzer B, Lane JE, McAdam AG, Humphries MM, and Boutin S
- Subjects
- Animals, Ecosystem, Predatory Behavior physiology, Taiga, Hares physiology, Lynx physiology, Sciuridae physiology, Wind
- Abstract
Wind speed can have multifaceted effects on organisms including altering thermoregulation, locomotion, and sensory reception. While forest cover can substantially reduce wind speed at ground level, it is not known if animals living in forests show any behavioural responses to changes in wind speed. Here, we explored how three boreal forest mammals, a predator and two prey, altered their behaviour in response to average daily wind speeds during winter. We collected accelerometer data to determine wind speed effects on activity patterns and kill rates of free-ranging red squirrels (n = 144), snowshoe hares (n = 101), and Canada lynx (n = 27) in Kluane, Yukon from 2015 to 2018. All 3 species responded to increasing wind speeds by changing the time they were active, but effects were strongest in hares, which reduced daily activity by 25%, and lynx, which increased daily activity by 25%. Lynx also increased the number of feeding events by 40% on windy days. These results highlight that wind speed is an important abiotic variable that can affect behaviour, even in forested environments., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
- Published
- 2022
- Full Text
- View/download PDF
28. Developing a classification system to assign activity states to two species of freshwater turtles.
- Author
-
Auge AC, Blouin-Demers G, and Murray DL
- Subjects
- Animals, Fresh Water, Water, Environment, Behavior, Animal, Turtles
- Abstract
Research in ecology often requires robust assessment of animal behaviour, but classifying behavioural patterns in free-ranging animals and in natural environments can be especially challenging. New miniaturised bio-logging devices such as accelerometers are increasingly available to record animal behaviour remotely, and thereby address the gap in knowledge related to behaviour of free-ranging animals. However, validation of these data is rarely conducted and classification model transferability across closely-related species is often not tested. Here, we validated accelerometer and water sensor data to classify activity states in two free-ranging freshwater turtle species (Blanding's turtle, Emydoidea blandingii, and Painted turtle, Chrysemys picta). First, using only accelerometer data, we developed a decision tree to separate motion from motionless states, and second, we included water sensor data to classify the animal as being motionless or in-motion on land or in water. We found that accelerometers separated in-motion from motionless behaviour with > 83% accuracy, whereas models also including water sensor data predicted states in terrestrial and aquatic locations with > 77% accuracy. Despite differences in values separating activity states between the two species, we found high model transferability allowing cross-species application of classification models. Note that reducing sampling frequency did not affect predictive accuracy of our models up to a sampling frequency of 0.0625 Hz. We conclude that the use of accelerometers in animal research is promising, but requires prior data validation and development of robust classification models, and whenever possible cross-species assessment should be conducted to establish model generalisability., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Auge et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
- Published
- 2022
- Full Text
- View/download PDF
29. Characterizing M-protein light chain glycosylation via mass spectrometry.
- Author
-
Miller ID, Kohlhagen MC, Ladwig PM, Dasari S, Kumar S, Dispenzieri A, Willrich MAV, and Murray DL
- Subjects
- Humans, Glycosylation, Gas Chromatography-Mass Spectrometry, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization methods, Polysaccharides chemistry, Paraproteinemias, Monoclonal Gammopathy of Undetermined Significance
- Abstract
Objectives: Monoclonal gammopathy of undetermined significance (MGUS) patients with M-proteins containing n-glycosylated light chains (GLC) have an increased risk for progression to symptomatic plasma cell disorders (PCD). Large-scale research involving the determination of glycan specific moieties is understudied due to the lack of clinically viable methods. This report documents a proof-of-concept glycan characterization method for patients with M-protein GLCs., Design and Methods: Twenty-three previously characterized MGUS patients with glycosylated light chains identified by MASS-FIX were used for this study. Glycosylated light chains were enriched from patient serum using light chain (LC) specific Sepharose nanobody beads (NB), followed by glycan digestion via PNGase F. Glycan moieties were derivatized on-target using Girard's reagent T for MALDI-TOF analysis and confirmed with top-down GLC LC-ESI-Q-TOF-MS analysis., Results: Intact GLC LC-ESI-Q-TOF-MS and cleaved glycan MALDI-TOF MS analysis had 100% agreement for the top three intensity glycans between spectra and 88 percent agreement for all reported glycan moieties. GLC moieties among patients were similar with fucosylation being the only notable difference. Additionally, doubly glycosylated light chains were observed in two patients., Conclusions: The MALDI-TOF method provides the tools to characterize and evaluate GLCs in a clinical setting as it is adaptable to our clinical MASS-Fix assay, relatively cheap, and accurate in glycan moiety assignments as confirmed by top-down GLC LC-ESI-Q-TOF-MS., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Inc.)
- Published
- 2022
- Full Text
- View/download PDF
30. Correction: Mu heavy chain disease with MYD88 L265P mutation: An unusual manifestation of lymphoplasmacytic lymphoma.
- Author
-
Baloda V, Wheeler SE, Murray DL, Kohlhagen MC, Vos JA, Yatsenko SA, Agha ME, Djokic M, Swerdlow SH, and Bailey NG
- Published
- 2022
- Full Text
- View/download PDF
31. Comparison of two free light chain assays: performance of the involved free light chain ratio and implications for diagnosis of multiple myeloma.
- Author
-
Willrich MAV, Murray DL, Rajkumar SV, Bryant SC, Larson D, Pazdernik V, Snyder MR, Kyle RA, and Dispenzieri A
- Subjects
- Humans, Immunoglobulin Light Chains, Immunoglobulin kappa-Chains, Multiple Myeloma diagnosis
- Published
- 2022
- Full Text
- View/download PDF
32. Mu heavy chain disease with MYD88 L265P mutation: an unusual manifestation of lymphoplasmacytic lymphoma.
- Author
-
Baloda V, Wheeler SE, Murray DL, Kohlhagen MC, Vos JA, Yatsenko SA, Agha ME, Djokic M, Swerdlow SH, and Bailey NG
- Subjects
- Humans, Mutation, Myeloid Differentiation Factor 88 genetics, Heavy Chain Disease, Leukemia, Lymphocytic, Chronic, B-Cell diagnosis, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Lymphocytosis, Lymphoma, Waldenstrom Macroglobulinemia diagnosis, Waldenstrom Macroglobulinemia genetics, Waldenstrom Macroglobulinemia pathology
- Abstract
Background: Mu heavy chain disease is a rare lymphoid neoplasm characterized by vacuolated bone marrow plasma cells and secretion of defective mu immunoglobulin heavy chains. The biological basis of mu heavy chain disease is poorly understood., Case Presentation: We report a case of mu heavy chain disease with MYD88 L265P mutation and deletion of 6q, genetic aberrations that are both strongly associated with lymphoplasmacytic lymphoma/Waldenström macroglobulinemia. Identification of the truncated mu immunoglobulin was facilitated by mass spectrometric analysis of the patient's serum., Conclusions: Mu heavy chain disease has been described as similar to chronic lymphocytic leukemia; however, the frequency of lymphocytosis in mu heavy chain disease has not been previously reported. We reviewed all previously published mu heavy chain disease reports and found that lymphocytosis is uncommon in the entity. This finding, along with the emerging genetic feature of recurrent MYD88 mutation in mu heavy chain disease, argues that at least a significant subset of cases are more similar to lymphoplasmacytic lymphoma than to chronic lymphocytic leukemia., (© 2022. The Author(s).)
- Published
- 2022
- Full Text
- View/download PDF
33. The characteristics of seronegative and seropositive non-hepatitis-associated cryoglobulinemic glomerulonephritis.
- Author
-
Javaugue V, Valeri AM, Jaffer Sathick I, Said SM, Erdogan Damgard S, Murray DL, Klobucher T, Andeen NK, Sethi S, Fervenza FC, Leung N, and Nasr SH
- Subjects
- Cryoglobulins, Humans, Middle Aged, Retrospective Studies, Glomerulonephritis diagnosis, Glomerulonephritis etiology, Glomerulonephritis pathology, Paraproteinemias pathology, Renal Insufficiency
- Abstract
The clinicopathologic characteristics and long-term outcome of non-hepatitis-associated cryoglobulinemic glomerulonephritis (CryoGN) are not well-defined and cases with undetectable serum cryoglobulin (seronegative CryoGN) have not been investigated. To resolve this, we retrospectively identified 81 patients with biopsy-proven non-hepatitis CryoGN, including 22 with seronegative CryoGN. The median age was 61 years and 76% presented with nephritic syndrome. A hematologic condition was found in 89% of patients, including monoclonal gammopathy of renal significance (65%) and symptomatic lymphoproliferative disorder (35%). In the seropositive group, 56% had type II, 29% type I, and 8% type III cryoglobulin. Extrarenal manifestations, mostly of skin, were present in 64% and were significantly less common in seronegative CryoGN. Glomerular deposits by immunofluorescence were IgM dominant (84%) and polytypic (70%) in the seropositive group, whereas 52% of seronegative cases had monotypic deposits (i.e., type I cryoglobulin). Ultrastructurally, the deposits were organized in 77% of cases. Substructure appearance significantly differed according to the type of CryoGN, forming most commonly short cylindrical structures in type II and other organized substructures in type I CryoGN. Most patients were treated with clone-directed therapy. On follow up (median 33 months), 77% had partial or complete remission, 10% reached kidney failure and 14% died. Predictors of kidney failure on univariate analysis were AKIN stage 3, positive rheumatoid factor and biclonal gammopathy at diagnosis. We conclude that most CryoGN cases (types I and II) are due to a hematologic condition and are associated with favorable outcome after clone-directed therapy. Seronegative CryoGN accounts for about a quarter of cases and is mostly a kidney-limited disease. Thus, further investigations are needed to unravel the pathophysiology of seronegative CryoGN., (Copyright © 2022 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
34. Monoclonal and oligoclonal anti-platelet factor 4 antibodies mediate VITT.
- Author
-
Kanack AJ, Bayas A, George G, Abou-Ismail MY, Singh B, Kohlhagen MC, Splinter NP, Christ M, Naumann M, Moser KA, Smock KJ, Grazioli A, Wen R, Wang D, Murray DL, and Padmanabhan A
- Subjects
- Antibodies, Monoclonal therapeutic use, Humans, Immunoglobulin G, Immunologic Factors, Platelet Factor 4, Purpura, Thrombocytopenic, Idiopathic
- Published
- 2022
- Full Text
- View/download PDF
35. Prevalence of heavy chain MGUS by race and family history risk groups using a high-sensitivity screening method.
- Author
-
Vachon CM, Murray J, Allmer C, Larson D, Norman AD, Sinnwell JP, Dispenzieri A, Kleinstern G, Visram A, Kyle RA, Rajkumar SV, Slager SL, Kumar SK, and Murray DL
- Subjects
- Humans, Middle Aged, Prevalence, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, United States, Monoclonal Gammopathy of Undetermined Significance diagnosis, Monoclonal Gammopathy of Undetermined Significance epidemiology, Multiple Myeloma epidemiology, Paraproteinemias
- Abstract
Mass-spectrometry (MS) assays detect lower levels of monoclonal proteins and result in earlier detection of monoclonal gammopathy of undetermined significance (MGUS). We examined heavy chain MGUS prevalence using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS among 3 risk groups, ages 50 or older: 327 African Americans (AA) and 1223 European Americans (EA) from a clinical biobank and 1093 unaffected first-degree relatives (FDR) of patients with hematologic disorders. Age- and sex-adjusted prevalence rates were directly standardized to 2010 United States population. Prevalence ratios were estimated for comparisons of AA and FDR to the EA group using the Poisson distribution. Results were also compared with population-based prevalence using conventional gel-based methods. Risk groups had similar sex and age distributions. MALDI-TOF MGUS prevalence was higher in the AA (16.5% [95% confidence interval (CI), 12.2%, 20.8%]) and FDR (18.3% [95% CI, 16.6%, 21.6%]) than in EA (10.8% [95% CI, 8.8%, 12.7%]), translating to prevalence ratios of 1.73 (95% CI, 1.31, 2.29) and 1.90 (95% CI, 1.55, 2.34), respectively. MALDI-TOF EA prevalence was over threefold higher than conventional estimates but showed similar age trends. Thus, the MALDI-TOF assay found greater numbers with MGUS but similar relative differences by race, family history, and age as prior studies., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
36. Bringing mass spectrometry into the care of patients with multiple myeloma.
- Author
-
Murray DL
- Subjects
- Antibodies, Monoclonal therapeutic use, Humans, Neoplasm, Residual, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization methods, Multiple Myeloma diagnosis, Multiple Myeloma therapy
- Abstract
Serum protein electrophoresis methods are widely employed to detect, quantify and isotype M-proteins for multiple myeloma patients. Increasing clinical demands to detect residual disease and interferences from new therapeutic monoclonal antibody treatments have stretched electrophoretic methods to their analytical limits. Newer techniques to detect M-proteins using mass spectrometry (MS) are emerging with improved clinical and analytical performance. These techniques are beginning to gain traction within the routine clinical lab testing. This review describes these MS methods with attention to the current and future roles such testing could play in the care of multiple myeloma patients., (© 2022. Japanese Society of Hematology.)
- Published
- 2022
- Full Text
- View/download PDF
37. Laboratory Detection and Initial Diagnosis of Monoclonal Gammopathies.
- Author
-
Keren DF, Bocsi G, Billman BL, Etzell J, Faix JD, Kumar S, Lipe B, McCudden C, Montgomery R, Murray DL, Rai AJ, Redondo TC, Souter L, Ventura CB, and Ansari MQ
- Subjects
- Humans, Laboratories, Systematic Reviews as Topic, Paraproteinemias diagnosis
- Abstract
Context.—: The process for identifying patients with monoclonal gammopathies is complex. Initial detection of a monoclonal immunoglobulin protein (M protein) in the serum or urine often requires compilation of analytical data from several areas of the laboratory. The detection of M proteins depends on adequacy of the sample provided, available clinical information, and the laboratory tests used., Objective.—: To develop an evidence-based guideline for the initial laboratory detection of M proteins., Design.—: To develop evidence-based recommendations, the College of American Pathologists convened a panel of experts in the diagnosis and treatment of monoclonal gammopathies and the laboratory procedures used for the initial detection of M proteins. The panel conducted a systematic literature review to address key questions. Using the Grading of Recommendations Assessment, Development, and Evaluation approach, recommendations were created based on the available evidence, strength of that evidence, and key judgements as defined in the Grading of Recommendations Assessment, Development, and Evaluation Evidence to Decision framework., Results.—: Nine guideline statements were established to optimize sample selection and testing for the initial detection and quantitative measurement of M proteins used to diagnose monoclonal gammopathies., Conclusions.—: This guideline was constructed to harmonize and strengthen the initial detection of an M protein in patients displaying symptoms or laboratory features of a monoclonal gammopathy. It endorses more comprehensive initial testing when there is suspicion of amyloid light chain amyloidosis or neuropathies, such as POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) syndrome, associated with an M protein., Competing Interests: Authors' disclosures of potential conflicts of interest and author contributions are found in the Appendix at the end of this article.
- Published
- 2022
- Full Text
- View/download PDF
38. Balancing food acquisition and predation risk drives demographic changes in snowshoe hare population cycles.
- Author
-
Majchrzak YN, Peers MJL, Studd EK, Menzies AK, Walker PD, Shiratsuru S, McCaw LK, Boonstra R, Humphries M, Jung TS, Kenney AJ, Krebs CJ, Murray DL, and Boutin S
- Subjects
- Animals, Ecosystem, Population Dynamics, Predatory Behavior, Seasons, Hares
- Abstract
Snowshoe hare cycles are one of the most prominent phenomena in ecology. Experimental studies point to predation as the dominant driving factor, but previous experiments combining food supplementation and predator removal produced unexplained multiplicative effects on density. We examined the potential interactive effects of food limitation and predation in causing hare cycles using an individual-based food-supplementation experiment over-winter across three cycle phases that naturally varied in predation risk. Supplementation doubled over-winter survival with the largest effects occurring in the late increase phase. Although the proximate cause of mortality was predation, supplemented hares significantly decreased foraging time and selected for conifer habitat, potentially reducing their predation risk. Supplemented hares also lost less body mass which resulted in the production of larger leverets. Our results establish a mechanistic link between how foraging time, mass loss and predation risk affect survival and reproduction, potentially driving demographic changes associated with hare cycles., (© 2022 John Wiley & Sons Ltd.)
- Published
- 2022
- Full Text
- View/download PDF
39. CSF Kappa Free Light Chains: Cutoff Validation for Diagnosing Multiple Sclerosis.
- Author
-
Saadeh RS, Bryant SC, McKeon A, Weinshenker B, Murray DL, Pittock SJ, and Willrich MAV
- Subjects
- Biomarkers, Humans, Oligoclonal Bands cerebrospinal fluid, Prospective Studies, Retrospective Studies, Multiple Sclerosis diagnosis
- Abstract
Objective: To determine and validate a cerebrospinal fluid (CSF) κ (KCSF) value statistically comparable to detection of CSF-specific oligoclonal bands (OCB) to support the diagnosis of multiple sclerosis (MS)., Patients and Methods: A total of 702 retrospective and 657 prospective paired CSF/serum samples from residual waste samples of physician-ordered OCB tests were obtained and tested for KCSF at Mayo Clinic. Charts were reviewed by a neurologist blinded to KCSF results. Specificity and sensitivity for MS diagnosis were evaluated to establish a diagnostic cutoff value for KCSF in the retrospective cohort and then validated in the prospective cohort., Results: Retrospective and prospective subgroups, respectively, included MS (n=85, 70), non-MS (n=615, 585), and undetermined diagnosis (excluded, n=2, 2). The retrospective data established a KCSF cutoff value of 0.1 mg/dL to be comparable to OCB testing. In the retrospective subgroup, KCSF vs OCB sensitivities for diagnosis of MS were 68.2% vs 75.0% (P=.08) and specificities were 86.1% vs 87.6% (P=.27). The KCSF area under the receiver operating characteristic curve was 0.772 (95% CI, 0.720 to 0.824), and for OCB was 0.813 (95% CI, 0.764 to 0.861). The prospective cohort was then used to validate the diagnostic KCSF value of 0.1 mg/dL; KCSF vs OCB sensitivities were 78.6% for both (P>.99) and specificities were 87.1% vs 89.4% (P=.09)., Conclusion: The KCSF value of 0.1 mg/dL is a valid alternative to OCB testing, offering a standardized quantitative measure, eliminating human error, reducing cost and turnaround time, with no significant difference in sensitivity and specificity. This study provides class I evidence that a KCSF value of 0.1 mg/dL can be used in place of OCB testing to support the diagnosis of MS., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
40. Kidney Transplantation in Patients With Monoclonal Gammopathy of Renal Significance (MGRS)-Associated Lesions: A Case Series.
- Author
-
Heybeli C, Alexander MP, Bentall AJ, Amer H, Buadi FK, Dean PG, Dingli D, Dispenzieri A, El Ters M, Gertz MA, Issa NS, Kapoor P, Kourelis T, Kukla A, Kumar S, Lacy MQ, Lorenz EC, Muchtar E, Murray DL, Nasr SH, Prieto M, Rajkumar SV, Schinstock CA, Stegall MD, Warsame R, and Leung N
- Subjects
- Humans, Kidney, Retrospective Studies, Kidney Diseases, Kidney Transplantation adverse effects, Monoclonal Gammopathy of Undetermined Significance, Paraproteinemias complications
- Abstract
Rationale & Objective: Data on kidney transplantation outcomes among patients with monoclonal gammopathy of renal significance (MGRS) are lacking., Study Design: Case series of patients with MGRS, some of whom received clone-directed therapies before kidney transplantation., Setting & Participants: 28 patients who underwent kidney transplantation from 1987 through 2016 after diagnosis with MGRS-associated lesions including light-chain deposition disease (LCDD), C3 glomerulopathy with monoclonal gammopathy (C3G-MG), and light-chain proximal tubulopathy (LCPT)., Findings: Of the 19 patients with LCDD, 10 were treated before kidney transplantation and 9 were treatment-naive. Among the treated patients with LCDD, 3 (30%) experienced histologic recurrence, 2 (20%) grafts failed, and 2 (20%) died during a median follow-up of 70 (range, 3-162) months after transplant. In the treatment-naive LCDD group, 8 (89%) had histologic recurrence, 6 (67%) grafts failed, and 4 (44%) patients died during a median follow-up of 60 (range, 35-117) months. Of the 5 patients who had a complete response before transplant, none died, and only 1 experienced graft failure, 162 months after transplant. Of 5 patients with C3G-MG, 3 were treatment-naive before transplant. Both patients who were treated before transplant had histologic recurrence, and 1 experienced graft failure and died. Among the 3 patients with treatment-naive C3G-MG, histologic recurrence occurred in all, and graft loss and death were observed in 2 and 1, respectively. In the LCPT group (n=4), histologic recurrence was observed in all 3 patients who did not receive clone-directed therapies before transplant, and 2 of these patients died, 1 with a functioning kidney. The 1 patient with LCPT who received therapy before transplant did not have histologic recurrence or graft loss and survived., Limitations: Small sample size, nonstandardized clinical management, retrospective design., Conclusions: Recurrence is very common in all MGRS-associated lesions after kidney transplant. Achieving a complete hematologic response may reduce the risks of recurrence, graft loss, and death. More studies are needed to determine the effects of hematologic response on outcomes for each MGRS-associated lesion., (Copyright © 2021 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
41. Detection of Plasma Cell Disorders by Mass Spectrometry: A Comprehensive Review of 19,523 Cases.
- Author
-
Dasari S, Kohlhagen MC, Dispenzieri A, Willrich MAV, Snyder MR, Kourelis TV, Lust JA, Mills JR, Kyle RA, and Murray DL
- Subjects
- Biomarkers blood, Blood Protein Electrophoresis methods, Female, Humans, Male, Mass Spectrometry, Middle Aged, Paraproteinemias blood, Sensitivity and Specificity, Immunoglobulin Light Chains blood, Immunoglobulin lambda-Chains blood, Paraproteinemias diagnosis
- Abstract
Objectives: To verify the analytical performance of a new mass spectrometry-based method, termed MASS-FIX, when screening for plasma cell disorders in a routine clinical laboratory., Patients and Methods: Results from 19,523 unique patients tested for an M-protein between July 24, 2018, and March 6, 2020, by a combination serum protein electrophoresis (SPEP) and MASS-FIX were examined for consistency with pretest implementation performance. MASS-FIX's ability to verify abnormal results from SPEP and free light chain measurements was then compared with that of immunofixation electrophoresis (IFE) using a separate cohort of 52,586 patients tested by SPEP/IFE during the same period., Results: Overall, 62.4% of our cohort was negative for an M-protein. Importantly, 7.3% of all specimens had an M spike on SPEP (0.1 to 8.5 g/dL) and MASS-FIX detected an M-protein in all these samples. Of all samples, 30.3% had M-proteins that were detected by MASS-FIX but the SPEP finding was too small for quantification. Of the positive samples, 5.7% contained a therapeutic monoclonal antibody. Of the positive samples, 4.1% had an N-glycosylated light chain (biomarker of high-risk plasma cell disorders). MASS-FIX confirmed a higher percentage of SPEP abnormalities than IFE. MASS-FIX was slightly more sensitive than IFE when confirming an M-protein in samples with an abnormal free light chain ratio. MASS-FIX had a very low sample repeat rate (1.5%). MASS-FIX was highly automatable resulting in a higher number of samples/technologist/day than IFE (∼30% more)., Conclusion: Overall, MASS-FIX was successful in maintaining validation characteristics. MASS-FIX was more sensitive in confirming SPEP abnormalities when compared with IFE. Ability to detect therapeutic monoclonal antibodies and glycosylated light chains was distinctly advantageous., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
42. Corrigendum to Heybeli C, Bentall A, Wen J, et al. A study from The Mayo Clinic evaluated long-term outcomes of kidney transplantation in patients with immunoglobulin light chain amyloidosis. Kidney Int. 2021;99:707-715.
- Author
-
Heybeli C, Bentall A, Wen J, Alexander MP, Buadi FK, Cosio FG, Dean PG, Dispenzieri A, Dingli D, El Ters M, Gertz MA, Amer H, Kapoor P, Khamash H, Kourelis T, Kumar S, Lorenz EC, Mai M, Muchtar E, Murray DL, Prieto M, Schinstock CA, Stegall MD, Warsame R, and Leung N
- Published
- 2021
- Full Text
- View/download PDF
43. MALDI-TOF mass spectrometry can distinguish immunofixation bands of the same isotype as monoclonal or biclonal proteins.
- Author
-
Fatica EM, Martinez M, Ladwig PM, Murray JD, Kohlhagen MC, Kyle RA, Kourelis T, Lust JA, Snyder MR, Dispenzieri A, Murray DL, and Willrich MAV
- Subjects
- Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal chemistry, Female, Humans, Immunoglobulin G blood, Immunoglobulin G chemistry, Male, Middle Aged, Multiple Myeloma blood, Myeloma Proteins chemistry, Protein Multimerization, Spectrometry, Mass, Electrospray Ionization, Antibodies, Monoclonal blood, Immunoelectrophoresis methods, Myeloma Proteins analysis, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization methods
- Abstract
Background: Plasma cell disorders (PCDs) are typically characterized by excessive production of a single immunoglobulin, defined as a monoclonal protein (M-protein). Some patients have more than one identifiable M-protein, termed biclonal. Traditional immunofixation electrophoresis (IFE) cannot distinguish if two bands of the same isotype represent biclonal proteins or M-proteins with some other feature. A novel assay using immunoenrichment coupled to matrix-assisted laser desorption ionization time-of-flight mass-spectrometry (Mass-Fix) was applied to determine whether two bands of the same isotype represented (1) monomers and dimers of a single M-protein, (2) an M-protein plus a therapeutic monoclonal antibody (t-mAb), (3) an M-protein with light chain glycosylation, or (4) two distinct biclonal M-proteins., Methods: Patient samples with two bands of the same isotype identified by IFE were enriched using nanobodies against IgG, IgA, IgM, or κ and λ light chains then analyzed by Mass-Fix. Light chain masses were used to differentiate IgGκ M-proteins from t-mAbs. Mass differences between peaks were calculated to identify N-glycosylation or matrix adducts. High-resolution mass spectrometry was used as a comparator method in a subset of samples., Results: Eighty-one residual samples were collected. For IgA, 93% (n = 25) were identified as monoclonal. For IgG, 67% (n = 24) were monoclonal, and 33% (n = 12) were truly biclonal. Among the monoclonal IgGs, the second band represented a glycosylated form for 21% (n = 5), while 33% (n = 8) had masses consistent with a t-mAb. 44% (n = 8) of IgM samples were biclonal, and 56% (n = 10) were monoclonal, of which one was glycosylated., Conclusions: We demonstrate the utility of mass spectrometry in the characterization of multiple IFE bands of the same isotype. Improved reporting accuracy of M-proteins is useful for monitoring of patients with PCDs., (Copyright © 2021 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
44. Food availability and long-term predation risk interactively affect antipredator response.
- Author
-
Shiratsuru S, Majchrzak YN, Peers MJL, Studd EK, Menzies AK, Derbyshire R, Humphries MM, Krebs CJ, Murray DL, and Boutin S
- Subjects
- Animals, Yukon Territory, Food Chain, Predatory Behavior
- Abstract
Food availability and temporal variation in predation risk are both important determinants of the magnitude of antipredator responses, but their effects have rarely been examined simultaneously, particularly in wild prey. Here, we determine how food availability and long-term predation risk affect antipredator responses to acute predation risk by monitoring the foraging response of free-ranging snowshoe hares (Lepus americanus) to an encounter with a Canada lynx (Lynx canadensis) in Yukon, Canada, over four winters (2015-2016 to 2018-2019). We examined how this response was influenced by natural variation in long-term predation risk (2-month mortality rate of hares) while providing some individuals with supplemental food. On average, snowshoe hares reduced foraging time up to 10 h after coming into close proximity (≤75 m) with lynx, and reduced foraging time an average of 15.28 ± 7.08 min per lynx encounter. Hares tended to respond more strongly when the distance to lynx was shorter. More importantly, the magnitude of hares' antipredator response to a lynx encounter was affected by the interaction between food-supplementation and long-term predation risk. Food-supplemented hares reduced foraging time more than control hares after a lynx encounter under low long-term risk, but decreased the magnitude of the response as long-term risk increased. In contrast, control hares increased the magnitude of their response as long-term risk increased. Our findings show that food availability and long-term predation risk interactively drive the magnitude of reactive antipredator response to acute predation risk. Determining the factors driving the magnitude of antipredator responses would contribute to a better understanding of the indirect effects of predators on prey populations., (© 2021 by the Ecological Society of America.)
- Published
- 2021
- Full Text
- View/download PDF
45. Belantamab mafodotin detection by MASS-FIX and immunofixation.
- Author
-
Mellors PW, Kohlhagen MC, Dasari S, Willrich MAV, Gertz MA, Kumar SK, Lacy MQ, Murray DL, and Dispenzieri A
- Subjects
- Humans, Immunoelectrophoresis, Immunologic Tests, Antibodies, Monoclonal, Humanized, Multiple Myeloma
- Published
- 2021
- Full Text
- View/download PDF
46. Correction: MASS-FIX for the detection of monoclonal proteins and light chain N-glycosylation in routine clinical practice: a cross-sectional study of 6315 patients.
- Author
-
Mellors PW, Dasari S, Kohlhagen MC, Kourelis T, Go RS, Muchtar E, Gertz MA, Kumar SK, Buadi FK, Willrich MAV, Lust JA, Kapoor P, Lacy MQ, Dingli D, Hwa Y, Fonder A, Hobbs M, Hayman S, Warsame R, Leung NR, Lin Y, Gonsalves W, Siddiqui M, Kyle RA, Rajkumar SV, Murray DL, and Dispenzieri A
- Published
- 2021
- Full Text
- View/download PDF
47. Clearing drug interferences in myeloma treatment using mass spectrometry.
- Author
-
Kohlhagen MC, Mills JR, Willrich MAV, Dasari S, Dispenzieri A, and Murray DL
- Subjects
- Antineoplastic Agents administration & dosage, Antineoplastic Agents blood, Blood Protein Electrophoresis, Chromatography, Liquid, Humans, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Antibodies, Monoclonal administration & dosage, Antibodies, Monoclonal blood, Antibodies, Monoclonal, Humanized administration & dosage, Antibodies, Monoclonal, Humanized blood, Multiple Myeloma blood, Multiple Myeloma drug therapy, Myeloma Proteins isolation & purification
- Abstract
Objective: To explore the possibility of using a combination of a rapid MALDI-TOF-MS method (Mass-Fix) in conjunction with higher resolution LC-ESI-QTOF-MS (miRAMM) measurements to discriminate the IgG kappa M-protein from daratumumab, elotuzumab and isatuximab in myeloma patients., Design & Methods: 86 patients with an IgG kappa M-protein were spiked with therapeutic levels of the drugs and examined by Mass-Fix and miRAMM to establish the percent of cases that could be resolved by each method. The method was then applied to 21 samples from patients receiving one of the drugs., Results: Mass-Fix was capable of resolving the t-mAb from M-protein for 87 percent of the spiked samples. For the cases unresolved by Mass-Fix, miRAMM was capable of resolving the remaining drug interferences. The 21 IgG kappa myeloma patients that were receiving the drugs were all resolved by Mass-Fix., Conclusion: This proposed algorithm allows use of a clinical available assay (Mass-Fix) while maximizing the number of cases that can accurately resolve the t-mAb from the M-protein., (Copyright © 2021. Published by Elsevier Inc.)
- Published
- 2021
- Full Text
- View/download PDF
48. Treatment of AL Amyloidosis: Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) Consensus Statement 2020 Update.
- Author
-
Muchtar E, Dispenzieri A, Gertz MA, Kumar SK, Buadi FK, Leung N, Lacy MQ, Dingli D, Ailawadhi S, Bergsagel PL, Fonseca R, Hayman SR, Kapoor P, Grogan M, Abou Ezzeddine OF, Rosenthal JL, Mauermann M, Siddiqui M, Gonsalves WI, Kourelis TV, Larsen JT, Reeder CB, Warsame R, Go RS, Murray DL, McPhail ED, Dasari S, Jevremovic D, Kyle RA, Lin Y, Lust JA, Russell SJ, Hwa YL, Fonder AL, Hobbs MA, Rajkumar SV, Roy V, and Sher T
- Subjects
- Humans, Immunoglobulin Light-chain Amyloidosis diagnosis, Risk Assessment, Immunoglobulin Light-chain Amyloidosis therapy, Multiple Myeloma therapy
- Abstract
Immunoglobulin light chain (AL) amyloidosis is a clonal plasma cell disorder leading to progressive and life-threatening organ failure. The heart and the kidneys are the most commonly involved organs, but almost any organ can be involved. Because of the nonspecific presentation, diagnosis delay is common, and many patients are diagnosed with advanced organ failure. In the era of effective therapies and improved outcomes for patients with AL amyloidosis, the importance of early recognition is further enhanced as the ability to reverse organ dysfunction is limited in those with a profound organ failure. As AL amyloidosis is an uncommon disorder and given patients' frailty and high early death rate, management of this complex condition is challenging. The treatment of AL amyloidosis is based on various anti-plasma cell therapies. These therapies are borrowed and customized from the treatment of multiple myeloma, a more common disorder. However, a growing number of phase 2/3 studies dedicated to the AL amyloidosis population are being performed, making treatment decisions more evidence-based. Supportive care is an integral part of management of AL amyloidosis because of the inherent organ dysfunction, limiting the delivery of effective therapy. This extensive review brings an updated summary on the management of AL amyloidosis, sectioned into the 3 pillars for survival improvement: early disease recognition, anti-plasma cell therapy, and supportive care., (Copyright © 2021 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
49. Clinical Mass Spectrometry Approaches to Myeloma and Amyloidosis.
- Author
-
Murray DL and Dasari S
- Subjects
- Humans, Mass Spectrometry, Proteomics, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Amyloidosis diagnosis, Multiple Myeloma diagnosis, Paraproteinemias
- Abstract
The diagnosis of myeloma and other plasma cell disorders has traditionally been done with the aid of electrophoretic methods, whereas amyloidosis has been characterized by immunohistochemistry. Mass spectrometry has recently been established as an alternative to these traditional methods and has been proved to bring added benefit for patient care. These newer mass spectrometry-based methods highlight some of the key advantages of modern proteomic methods and how they can be applied to the routine care of patients., Competing Interests: Disclosure The authors have intellectual property rights on the use of MS in monoclonal gammopathies licensed to The Binding Site., (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
50. IGVL gene region usage correlates with distinct clinical presentation in IgM vs non-IgM light chain amyloidosis.
- Author
-
Sidana S, Dasari S, Kourelis TV, Dispenzieri A, Murray DL, King RL, McPhail ED, Ramirez-Alvarado M, Kumar SK, and Gertz MA
- Subjects
- Humans, Immunoglobulin Light Chains, Immunoglobulin M, Amyloidosis diagnosis, Amyloidosis genetics, Immunoglobulin Light-chain Amyloidosis diagnosis
- Abstract
Patients with immunoglobulin M (IgM) light chain (AL) amyloidosis have a distinct clinical presentation compared with those with non-IgM amyloidosis. We hypothesized that differential immunoglobulin light-chain variable region (IGVL) gene usage may explain the differences in organ involvement, because IGVL usage correlates with organ tropism. IGVL usage was evaluated by mass spectrometry of amyloid deposits (IgM, n = 45; non-IgM, n = 391) and differed across the 2 groups. In the λ family, LV2-08 (13% vs 2%; P < .001) and LV2-14 (36% vs 10%; P < .001) usage was more common in IgM vs non-IgM amyloidosis, whereas LV1-44 (0% vs 10%; P = .02) and LV6-57 (2% vs 18%; P = .004) usage was less common. In the κ family, there was a trend toward higher KV4-01 (11% vs 4%; P = .06) usage in IgM amyloidosis. IGVL usage correlated with disease characteristics/organ tropism. LV2-14 (more common in IgM amyloidosis) has historically been associated with peripheral nerve involvement and lower light chain burden, which were more frequent in IgM amyloidosis. LV1-44 (less common in IgM), associated with cardiac involvement, was less frequent in IgM patients. LV6-57 (less common in IgM) is associated with t(11;14), which was less frequent in IgM patients. In conclusion, IGVL gene usage differs in patients with IgM vs non-IgM amyloidosis and may explain the distinct clinical presentation., (© 2021 by The American Society of Hematology.)
- Published
- 2021
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.