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1. Performance evaluation of the Streck ARM-DⓇKit, β-Lactamase for molecular detection of acquired β-lactamase genes

Author: Yoo, Brian B., Yamamoto, Norihisa, Quintero, Justina Ilutsik, Machado, Maria Jose, Sabour, Sarah, Blosser, Sara, Karlsson, Maria, Rasheed, James Kamile, and Brown, Allison C.
Abstract: •The streck ARM-DⓇKit, β-Lactamase assay was able to accurately identify 164 β-lactamase genes in 113 well-characterized bacterial isolates from the CDC & FDA antibiotic resistance isolate bank.•The evaluation included Acinetobacter baumanniicomplex, Pseudomonas aeruginosa,and 15 species of Enterobacterales.Isolates in the panel carried 49 different β-lactamase variants, representing the AmpC, ESBL, and carbapenemase genes most frequently detected in the United States.•The streck ARM-DⓇKit, β-Lactamase assay demonstrated >99% sensitivity and specificity compared with whole genome sequencing results for detection of β-lactamase gene variants.
Published: 2024
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2. Lignin Structure and Reactivity in the Organosolv Process Studied by NMR Spectroscopy, Mass Spectrometry, and Density Functional Theory

Author: Karlsson, Maria, Romson, Joakim, Elder, Thomas, Emmer, Åsa, and Lawoko, Martin
Abstract: There is need for well-defined lignin macromolecules for research related to their use in biomaterial and biochemical applications. Lignin biorefining efforts are therefore under investigation to meet these needs. The detailed knowledge of the molecular structure of the native lignin and of the biorefinery lignins is essential for understanding the extraction mechanisms as well as chemical properties of the molecules. The objective of this work was to study the reactivity of lignin during a cyclic organosolv extraction process adopting physical protection strategies. As references, synthetic lignins obtained by mimicking the chemistry of lignin polymerization were used. State-of-the-art nuclear magnetic resonance (NMR) analysis, a powerful tool for the elucidation of lignin inter-unit linkages and functionalities, is complemented with matrix-assisted laser desorption/ionization-time-of-flight-mass spectrometry (MALDI-TOF MS), to gain insights into linkage sequences and structural populations. The study unraveled interesting fundamental aspects on lignin polymerization processes, such as identifications of molecular populations with high degrees of structural homogeneity and the emergence of branching points in lignin structure. Furthermore, a previously proposed intramolecular condensation reaction is substantiated and new insights into the selectivity of this reaction are introduced and supported by density functional theory (DFT) calculations, where the important role of intramolecular π–π stacking is emphasized. The combined NMR and MALDI-TOF MS analytical approach, together with computational modeling, is important for deeper fundamental lignin studies and will be further exploited.
Published: 2023
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3. Epidemiology of extended-spectrum β-lactamase–producing Enterobacterales in five US sites participating in the Emerging Infections Program, 2017

Author: Duffy, Nadezhda, Karlsson, Maria, Reses, Hannah E., Campbell, Davina, Daniels, Jonathan, Stanton, Richard A., Janelle, Sarah J., Schutz, Kyle, Bamberg, Wendy, Rebolledo, Paulina A., Bower, Chris, Blakney, Rebekah, Jacob, Jesse T., Phipps, Erin C., Flores, Kristina G., Dumyati, Ghinwa, Kopin, Hannah, Tsay, Rebecca, Kainer, Marion A., Muleta, Daniel, Byrd-Warner, Benji, Grass, Julian E., Lutgring, Joseph D., Rasheed, J. Kamile, Elkins, Christopher A., Magill, Shelley S., and See, Isaac
Abstract: AbstractObjectiveThe incidence of infections from extended-spectrum β-lactamase (ESBL)–producing Enterobacterales (ESBL-E) is increasing in the United States. We describe the epidemiology of ESBL-E at 5 Emerging Infections Program (EIP) sites.MethodsDuring October–December 2017, we piloted active laboratory- and population-based (New York, New Mexico, Tennessee) or sentinel (Colorado, Georgia) ESBL-E surveillance. An incident case was the first isolation from normally sterile body sites or urine of Escherichia colior Klebsiella pneumoniae/oxytocaresistant to ≥1 extended-spectrum cephalosporin and nonresistant to all carbapenems tested at a clinical laboratory from a surveillance area resident in a 30-day period. Demographic and clinical data were obtained from medical records. The Centers for Disease Control and Prevention (CDC) performed reference antimicrobial susceptibility testing and whole-genome sequencing on a convenience sample of case isolates.ResultsWe identified 884 incident cases. The estimated annual incidence in sites conducting population-based surveillance was 199.7 per 100,000 population. Overall, 800 isolates (96%) were from urine, and 790 (89%) were E. coli. Also, 393 cases (47%) were community-associated. Among 136 isolates (15%) tested at the CDC, 122 (90%) met the surveillance definition phenotype; 114 (93%) of 122 were shown to be ESBL producers by clavulanate testing. In total, 111 (97%) of confirmed ESBL producers harbored a blaCTX-Mgene. Among ESBL-producing E. coliisolates, 52 (54%) were ST131; 44% of these cases were community associated.ConclusionsThe burden of ESBL-E was high across surveillance sites, with nearly half of cases acquired in the community. EIP has implemented ongoing ESBL-E surveillance to inform prevention efforts, particularly in the community and to watch for the emergence of new ESBL-E strains.
Published: 2022
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4. Fundamental Insights on the Physical and Chemical Properties of Organosolv Lignin from Norway Spruce Bark

Author: Rietzler, Barbara, Karlsson, Maria, Kwan, Isabella, Lawoko, Martin, and Ek, Monica
Abstract: The interest in the bark and the attempt to add value to its utilization have increased over the last decade. By applying an integrated bark biorefinery approach, it is possible to investigate the recovery of compounds that can be used to develop green and sustainable alternatives to fossil-based materials. In this work, the focus is on extracting Norway spruce (Picea abies) bark lignin via organosolv extraction. Following the removal of the extractives and the subcritical water extraction to remove the polysaccharides, a novel cyclic organosolv extraction procedure was applied, which enabled the recovery of lignin with high quality and preserved structure. Main indicators for low degradation and preservation of the lignin structure were a high β-O-4′ content and low amounts of condensed structures. Furthermore, high purity and low polydispersity of the lignin were observed. Thus, the obtained lignin exhibits high potential for use in the direct development of polymer precursors and other bio-based materials. During the extraction sequence, around 70% of the bark was extracted. Besides the lignin, the extractives as well as pectic polysaccharides and hemicelluloses were recovered with only minor degradation, which could potentially be used for the production of biofuel or other high-value products such as emulsifiers or adhesives.
Published: 2022
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5. Antimicrobial-resistant pathogens associated with pediatric healthcare-associated infections: Summary of data reported to the National Healthcare Safety Network, 2015–2017

Author: Weiner-Lastinger, Lindsey M., Abner, Sheila, Benin, Andrea L., Edwards, Jonathan R., Kallen, Alexander J., Karlsson, Maria, Magill, Shelley S., Pollock, Daniel, See, Isaac, Soe, Minn M., Walters, Maroya S., and Dudeck, Margaret A.
Abstract: AbstractObjective:To describe common pathogens and antimicrobial resistance patterns for healthcare-associated infections (HAIs) among pediatric patients that occurred in 2015–2017 and were reported to the Centers for Disease Control and Prevention’s National Healthcare Safety Network (NHSN).Methods:Antimicrobial resistance data were analyzed for pathogens implicated in central line-associated bloodstream infections (CLABSIs), catheter-associated urinary tract infections (CAUTIs), ventilator-associated pneumonias (VAPs), and surgical site infections (SSIs). This analysis was restricted to device-associated HAIs reported from pediatric patient care locations and SSIs among patients <18 years old. Percentages of pathogens with nonsusceptibility (%NS) to selected antimicrobials were calculated by HAI type, location type, and surgical category.Results:Overall, 2,545 facilities performed surveillance of pediatric HAIs in the NHSN during this period. Staphylococcus aureus(15%), Escherichia coli(12%), and coagulase-negative staphylococci (12%) were the 3 most commonly reported pathogens associated with pediatric HAIs. Pathogens and the %NS varied by HAI type, location type, and/or surgical category. Among CLABSIs, the %NS was generally lowest in neonatal intensive care units and highest in pediatric oncology units. Staphylococcusspp were particularly common among orthopedic, neurosurgical, and cardiac SSIs; however, E. coliwas more common in abdominal SSIs. Overall, antimicrobial nonsusceptibility was less prevalent in pediatric HAIs than in adult HAIs.Conclusion:This report provides an updated national summary of pathogen distributions and antimicrobial resistance patterns among pediatric HAIs. These data highlight the need for continued antimicrobial resistance tracking among pediatric patients and should encourage the pediatric healthcare community to use such data when establishing policies for infection prevention and antimicrobial stewardship.
Published: 2020
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6. Antimicrobial-resistant pathogens associated with adult healthcare-associated infections: Summary of data reported to the National Healthcare Safety Network, 2015–2017

Author: Weiner-Lastinger, Lindsey M., Abner, Sheila, Edwards, Jonathan R., Kallen, Alexander J., Karlsson, Maria, Magill, Shelley S., Pollock, Daniel, See, Isaac, Soe, Minn M., Walters, Maroya S., and Dudeck, Margaret A.
Abstract: AbstractObjective:Describe common pathogens and antimicrobial resistance patterns for healthcare-associated infections (HAIs) that occurred during 2015–2017 and were reported to the Centers for Disease Control and Prevention’s (CDC’s) National Healthcare Safety Network (NHSN).Methods:Data from central line-associated bloodstream infections (CLABSIs), catheter-associated urinary tract infections (CAUTIs), ventilator-associated events (VAEs), and surgical site infections (SSIs) were reported from acute-care hospitals, long-term acute-care hospitals, and inpatient rehabilitation facilities. This analysis included device-associated HAIs reported from adult location types, and SSIs among patients ≥18 years old. Percentages of pathogens with nonsusceptibility (%NS) to selected antimicrobials were calculated for each HAI type, location type, surgical category, and surgical wound closure technique.Results:Overall, 5,626 facilities performed adult HAI surveillance during this period, most of which were general acute-care hospitals with <200 beds. Escherichia coli(18%), Staphylococcus aureus(12%), and Klebsiellaspp (9%) were the 3 most frequently reported pathogens. Pathogens varied by HAI and location type, with oncology units having a distinct pathogen distribution compared to other settings. The %NS for most pathogens was significantly higher among device-associated HAIs than SSIs. In addition, pathogens from long-term acute-care hospitals had a significantly higher %NS than those from general hospital wards.Conclusions:This report provides an updated national summary of pathogen distributions and antimicrobial resistance among select HAIs and pathogens, stratified by several factors. These data underscore the importance of tracking antimicrobial resistance, particularly in vulnerable populations such as long-term acute-care hospitals and intensive care units.
Published: 2020
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7. β-Lactamase–Producing, Ciprofloxacin-Resistant Neisseria meningitidisIsolated From a 5-Month-Old Boy in the United States

Author: Taormina, Gillian, Campos, Joseph, Sweitzer, John, Retchless, Adam C, Lunquest, Kristy, McNamara, Lucy A, Reese, Natashia, Karlsson, Maria, and Hanisch, Benjamin
Abstract: Worldwide, there have been few reports of β-lactamases causing penicillin resistance in Neisseria meningitidis. The first known case of disease in the United States due to a β-lactamase-producing, ciprofloxacin-resistant N. meningitidiswas recently identified. This has potential implications on standard laboratory testing and empiric management of meningococcal disease.
Published: 2021
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8. Evaluation of Discrepancies in Carbapenem Minimum Inhibitory Concentrations Obtained at Clinical Laboratories Compared to a Public Health Laboratory

Author: Grass, Julian E., Magill, Shelley S., See, Isaac, Ansari, Uzma, Wilson, Lucy E., Vaeth, Elisabeth, Vagnone, Paula Snippes, Pattee, Brittany, Jacob, Jesse T., Program, Georgia Emerging Infections, Bower, Chris, Center, Atlanta Veterans Affairs Medical, Education, Foundation for Atlanta Veterans, Research, Satola, Sarah W., Janelle, Sarah J., Schutz, Kyle, Tsay, Rebecca, Kainer, Marion A., Muleta, Daniel, Cassidy, P. Maureen, Leung, Vivian H., Maloney, Meghan, Phipps, Erin C., Program, New Mexico Emerging Infections, Flores, Kristina G., Program, New Mexico Emerging Infections, Epson, Erin, Nadle, Joelle, Karlsson, Maria, and Lutgring, Joseph D.
Abstract: Background:Automated testing instruments (ATIs) are commonly used by clinical microbiology laboratories to perform antimicrobial susceptibility testing (AST), whereas public health laboratories may use established reference methods such as broth microdilution (BMD). We investigated discrepancies in carbapenem minimum inhibitory concentrations (MICs) among Enterobacteriaceae tested by clinical laboratory ATIs and by reference BMD at the CDC. Methods:During 2016–2018, we conducted laboratory- and population-based surveillance for carbapenem-resistant Enterobacteriaceae (CRE) through the CDC Emerging Infections Program (EIP) sites (10 sites by 2018). We defined an incident case as the first isolation of Enterobacterspp (E. cloacaecomplex or E. aerogenes), Escherichia coli, Klebsiella pneumoniae, K. oxytoca, or K. variicolaresistant to doripenem, ertapenem, imipenem, or meropenem from normally sterile sites or urine identified from a resident of the EIP catchment area in a 30-day period. Cases had isolates that were determined to be carbapenem-resistant by clinical laboratory ATI MICs (MicroScan, BD Phoenix, or VITEK 2) or by other methods, using current Clinical and Laboratory Standards Institute (CLSI) criteria. A convenience sample of these isolates was tested by reference BMD at the CDC according to CLSI guidelines. Results:Overall, 1,787 isolates from 112 clinical laboratories were tested by BMD at the CDC. Of these, clinical laboratory ATI MIC results were available for 1,638 (91.7%); 855 (52.2%) from 71 clinical laboratories did not confirm as CRE at the CDC. Nonconfirming isolates were tested on either a MicroScan (235 of 462; 50.9%), BD Phoenix (249 of 411; 60.6%), or VITEK 2 (371 of 765; 48.5%). Lack of confirmation was most common among E. coli(62.2% of E. coliisolates tested) and Enterobacterspp (61.4% of Enterobacterisolates tested) (Fig. 1A), and among isolates testing resistant to ertapenem by the clinical laboratory ATI (52.1%, Fig. 1B). Of the 1,388 isolates resistant to ertapenem in the clinical laboratory, 1,006 (72.5%) were resistant only to ertapenem. Of the 855 nonconfirming isolates, 638 (74.6%) were resistant only to ertapenem based on clinical laboratory ATI MICs. Conclusions:Nonconfirming isolates were widespread across laboratories and ATIs. Lack of confirmation was most common among E. coliand Enterobacterspp. Among nonconfirming isolates, most were resistant only to ertapenem. These findings may suggest that ATIs overcall resistance to ertapenem or that isolate transport and storage conditions affect ertapenem resistance. Further investigation into this lack of confirmation is needed, and CRE case identification in public health surveillance may need to account for this phenomenon.Funding:NoneDisclosures:None
Published: 2020
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9. High-throughput stem cell-based phenotypic screening through micronichesElectronic supplementary information (ESI) available. See DOI: 10.1039/c8bm01180j

Author: Kolb, Laura, Allazetta, Simone, Karlsson, Maria, Girgin, Mehmet, Weber, Wilfried, and Lutolf, Matthias P.
Abstract: As the field of tissue engineering develops, methods for screening combinations of signals for their effects on stem cell behavior are needed. We introduce a microgel-based screening platform for testing combinations of in situ-generated proteins on stem cell fate in ultrahigh-throughput. Compartmentalizing individual sets of growth factors was addressed by encapsulating aggregates of stable recombinant cell lines secreting individual glycoproteins into microgels through an on-chip polymerization. When these ‘microniches’ are cultured with a cell type of interest, fluorescence reporters indicate positive niches that perform the desired function, and the underlying producer cell lines of these selected microniches are analyzed by barcoded RNA sequencing. The microniche-based screening work-flow was validated viaa model system based on engineered mammalian cells expressing yellow fluorescent protein (YFP) upon anti-inflammatory cytokine interleukin 4 (IL4)-based activation.
Published: 2019
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10. Epidemiology, Clinical Presentation, Laboratory Diagnosis, Antimicrobial Resistance, and Antimicrobial Management of Invasive SalmonellaInfections

Author: Crump, John A., Sjölund-Karlsson, Maria, Gordon, Melita A., and Parry, Christopher M.
Abstract: SUMMARYSalmonella entericainfections are common causes of bloodstream infection in low-resource areas, where they may be difficult to distinguish from other febrile illnesses and may be associated with a high case fatality ratio. Microbiologic culture of blood or bone marrow remains the mainstay of laboratory diagnosis. Antimicrobial resistance has emerged in Salmonella enterica, initially to the traditional first-line drugs chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole. Decreased fluoroquinolone susceptibility and then fluoroquinolone resistance have developed in association with chromosomal mutations in the quinolone resistance-determining region of genes encoding DNA gyrase and topoisomerase IV and also by plasmid-mediated resistance mechanisms. Resistance to extended-spectrum cephalosporins has occurred more often in nontyphoidal than in typhoidal Salmonellastrains. Azithromycin is effective for the management of uncomplicated typhoid fever and may serve as an alternative oral drug in areas where fluoroquinolone resistance is common. In 2013, CLSI lowered the ciprofloxacin susceptibility breakpoints to account for accumulating clinical, microbiologic, and pharmacokinetic-pharmacodynamic data suggesting that revision was needed for contemporary invasive Salmonellainfections. Newly established CLSI guidelines for azithromycin and Salmonella entericaserovar Typhi were published in CLSI document M100 in 2015.
Published: 2015
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11. Development of a Pefloxacin Disk Diffusion Method for Detection of Fluoroquinolone-Resistant Salmonella enterica

Author: Skov, Robert, Matuschek, Erika, Sjölund-Karlsson, Maria, Åhman, Jenny, Petersen, Andreas, Stegger, Marc, Torpdahl, Mia, and Kahlmeter, Gunnar
Abstract: ABSTRACTFluoroquinolones (FQs) are among the drugs of choice for treatment of Salmonellainfections. However, fluoroquinolone resistance is increasing in Salmonelladue to chromosomal mutations in the quinolone resistance-determining regions (QRDRs) of the topoisomerase genes gyrA, gyrB, parC, and parEand/or plasmid-mediated quinolone resistance (PMQR) mechanisms including qnrvariants, aac(6')-Ib-cr, qepA, and oqxAB. Some of these mutations cause only subtle increases in the MIC, i.e., MICs ranging from 0.12 to 0.25 mg/liter for ciprofloxacin (just above the wild-type MIC of =0.06 mg/liter). These isolates are difficult to detect with standard ciprofloxacin disk diffusion, and plasmid-mediated resistance, such as qnr, is often not detected by the nalidixic acid screen test. We evaluated 16 quinolone/fluoroquinolone disks for their ability to detect low-level-resistant Salmonella entericaisolates that are not serotype Typhi. A total of 153 Salmonellaisolates characterized for the presence (n= 104) or absence (n= 49) of gyrAand/or parCtopoisomerase mutations, qnrA, qnrB, qnrD, qnrS, aac(6')-Ib-cr, or qepAgenes were investigated. All isolates were MIC tested by broth microdilution against ciprofloxacin, levofloxacin, and ofloxacin and by disk diffusion using EUCAST or CLSI methodology. MIC determination correctly categorized all isolates as either wild-type isolates (MIC of =0.06 mg/liter and absence of resistance genes) or non-wild-type isolates (MIC of >0.06 mg/liter and presence of a resistance gene). Disk diffusion using these antibiotics and nalidixic acid failed to detect some low-level-resistant isolates, whereas the 5-µg pefloxacin disk correctly identified all resistant isolates. However, pefloxacin will not detect isolates having aac(6')-Ib-cras the only resistance determinant. The pefloxacin disk assay was approved and implemented by EUCAST (in 2014) and CLSI (in 2015).
Published: 2015
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12. Co-infection with Babesia divergensand Anaplasma phagocytophilumin cattle (Bos taurus), Sweden

Author: Andersson, Martin O., Víchová, Bronislava, Tolf, Conny, Krzyzanowska, Sandra, Waldenström, Jonas, and Karlsson, Maria E.
Abstract: Babesiosis is a severe disease in cattle worldwide. In Europe, the main causative agent of bovine babesiosis is Babesia divergens. In some areas, this species is reported to have declined or even disappeared, and its etiological role overtaken by other piroplasmid species. Moreover, co-infection with other tick-transmitted pathogens can be expected to complicate diagnosis in cattle. Hence, molecular identification of the causative agent of babesiosis should be a priority. Therefore, samples from 71 domestic cattle, 39 with clinical signs of babesiosis and 32 without, from southern Sweden were screened for Babesiaspp. and Anaplasmaspp. using molecular methods Babesia divergenswas detected in 38 of the samples, and Anaplasma phagocytophilumin 17. Co-infections with both pathogens were frequent, occurring in 18% of the animals with a B. divergensinfection. The possibility of co-infection should be considered in diagnosis and treatment of bovine babesiosis.
Published: 2017
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13. Performance of Etest and Disk Diffusion for Detection of Ciprofloxacin and Levofloxacin Resistance in Salmonella enterica

Author: Deak, Eszter, Hindler, Janet A., Skov, Robert, Sjölund-Karlsson, Maria, Sokovic, Anita, and Humphries, Romney M.
Abstract: ABSTRACTWe compared Etest and disk diffusion to broth microdilution for the detection of fluoroquinolone resistance in 135 typhoidal and nontyphoidal serovars of Salmonella. Categorical agreements for the ciprofloxacin and levofloxacin Etests were 89.6 and 83.7%, respectively. Disk diffusion categorical agreements were 88.2 and 93.3%, respectively. Only minor errors were observed.
Published: 2014
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14. Fluoroquinolone Susceptibility Testing of Salmonella enterica: Detection of Acquired Resistance and Selection of Zone Diameter Breakpoints for Levofloxacin and Ofloxacin

Author: Sjölund-Karlsson, Maria, Howie, Rebecca L., Crump, John A., and Whichard, Jean M.
Abstract: ABSTRACTFluoroquinolones (e.g., ciprofloxacin) have become a mainstay for treating severe Salmonellainfections in adults. Fluoroquinolone resistance in Salmonellais mostly due to mutations in the topoisomerase genes, but plasmid-mediated quinolone resistance (PMQR) mechanisms have also been described. In 2012, the Clinical and Laboratory Standards Institute (CLSI) revised the ciprofloxacin interpretive criteria (breakpoints) for disk diffusion and MIC test methods for Salmonella. In 2013, the CLSI published MIC breakpoints for Salmonellato levofloxacin and ofloxacin, but breakpoints for assigning disk diffusion results to susceptible (S), intermediate (I), and resistant (R) categories are still needed. In this study, the MICs and inhibition zone diameters for nalidixic acid, ciprofloxacin, levofloxacin, and ofloxacin were determined for 100 clinical isolates of nontyphi Salmonellawith or without resistance mechanisms. We confirmed that the new levofloxacin MIC breakpoints resulted in the highest category agreement (94%) when plotted against the ciprofloxacin MICs and that the new ofloxacin MIC breakpoints resulted in 92% category agreement between ofloxacin and ciprofloxacin. By applying the new MIC breakpoints in the MIC zone scattergrams for levofloxacin and ofloxacin, the following disk diffusion breakpoints generated the least number of errors: =28 mm (S), 19 to 27 mm (I), and =18 mm (R) for levofloxacin and =25 mm (S), 16 to 24 mm (I), and =15 mm (R) for ofloxacin. Neither the levofloxacin nor the ofloxacin disk yielded good separation of isolates with and without resistance mechanisms. Further studies will be needed to develop a disk diffusion assay that efficiently detects all isolates with acquired resistance to fluoroquinolones.
Published: 2014
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15. Conditional DNA‐Protein Interactions Confer Stimulus‐Sensing Properties to Biohybrid Materials

Author: Christen, Erik H., Karlsson, Maria, Kämpf, Michael M., Schoenmakers, Ronald, Gübeli, Raphael J., Wischhusen, Hanna M., Friedrich, Christian, Fussenegger, Martin, and Weber, Wilfried
Abstract: Interactive materials that specifically respond to environmental stimuli hold high promise as energy‐autonomous sensors and actuators in biomedicine, analytics or microsystems engineering. However, the implementation of materials specifically responsive to a given small molecule has so far been hampered by a lack of generically applicable stimulus sensors. In this study, a novel and likely general strategy for the synthesis of biohybrid materials with desired stimulus specificity is established. The strategy is based on allosterically regulated DNA‐binding proteins, a conserved protein family that has evolved in prokaryotes to sense and respond to most diverse molecules in order to enable bacterial survival in a changing environment. The novel hydrogel design concept is demonstrated with the example of single‐chain TetR, a protein that binds the tetODNA motif and dissociates thereof in the presence of the antibiotic tetracycline. Therefore, linear polyacrylamide is crosslinked via the TetR/tetOinteraction to a biohybrid material that can subsequently be dissolved by tetracycline in a dose‐dependent manner. This drug‐induced dissolution is applied for the adjustable release of the cytokine interleukin 4 in a tetracycline‐dependent manner. The design concept developed in this study might serve as a blueprint for the synthesis of biohybrid materials responsive to drugs, metabolites or toxins by replacing TetR/tetOwith another protein/DNA pair showing the desired stimulus specificity.
Published: 2011
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16. Antimicrobial Susceptibility to Azithromycin among Salmonella entericaIsolates from the United States

Author: Sjölund-Karlsson, Maria, Joyce, Kevin, Blickenstaff, Karen, Ball, Takiyah, Haro, Jovita, Medalla, Felicita M., Fedorka-Cray, Paula, Zhao, Shaohua, Crump, John A., and Whichard, Jean M.
Abstract: ABSTRACTDue to emerging resistance to traditional antimicrobial agents, such as ampicillin, trimethoprim-sulfamethoxazole, and chloramphenicol, azithromycin is increasingly used for the treatment of invasive Salmonellainfections. In the present study, 696 isolates of non-Typhi Salmonellacollected from humans, food animals, and retail meats in the United States were investigated for antimicrobial susceptibility to azithromycin. Seventy-two Salmonella entericaserotype Typhi isolates from humans were also tested. For each isolate, MICs of azithromycin and 15 other antimicrobial agents were determined by broth microdilution. Among the non-Typhi Salmonellaisolates, azithromycin MICs among human isolates ranged from 1 to 32 μg/ml, whereas the MICs among the animal and retail meat isolates ranged from 2 to 16 μg/ml and 4 to 16 μg/ml, respectively. Among Salmonellaserotype Typhi isolates, the azithromycin MICs ranged from 4 to 16 μg/ml. The highest MIC observed in the present study was 32 μg/ml, and it was detected in three human isolates belonging to serotypes Kentucky, Montevideo, and Paratyphi A. Based on our findings, we propose an epidemiological cutoff value (ECOFF) for wild-type Salmonellaof ≤16 μg/ml of azithromycin. The susceptibility data provided could be used in combination with clinical outcome data to determine tentative clinical breakpoints for azithromycin and Salmonella enterica.
Published: 2011
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17. SalmonellaIsolates with Decreased Susceptibility to Extended-Spectrum Cephalosporins in the United States

Author: Sjölund-Karlsson, Maria, Rickert, Regan, Matar, Caline, Pecic, Gary, Howie, Rebecca L., Joyce, Kevin, Medalla, Felicita, Barzilay, Ezra J., and Whichard, Jean M.
Abstract: AbstractObjective:We describe the antimicrobial susceptibility to extended-spectrum cephalosporins in non-Typhi Salmonella(NTS) isolated from humans in the United States and explore resistance mechanisms for isolates displaying decreased susceptibility to ceftriaxone or ceftiofur. We further explore the concordance between the newly revised Clinical and Laboratory Standards Institute (CLSI) breakpoints for ceftriaxone and the presence of a β-lactamase.Methods:In 2005 and 2006, public health laboratories in all U.S. state health departments forwarded every 20th NTS isolate from humans to Centers for Disease Control and Prevention as part of the National Antimicrobial Resistance Monitoring System (NARMS) for enteric bacteria. Minimum inhibitory concentrations (MICs) were determined by broth microdilution. Isolates displaying decreased susceptibility (MIC ≥2 mg/L) to ceftriaxone or ceftiofur were included in the study. The presence of β-lactamase genes was investigated by polymerase chain reaction amplification and sequencing, targeting six different genes (blaTEM, blaOXA, blaSHV, blaCTX-M, blaPSE, and blaCMY). Plasmid location of blaCMYwas confirmed by transforming plasmids into Escherichia coli.Results:Among the 4236 isolates of NTS submitted to NARMS in 2005 and 2006, 175 (4.1%) displayed decreased susceptibility to either ceftriaxone or ceftiofur. By polymerase chain reaction screening, one or more β-lactamase genes could be detected in 139 (80.8%) isolates. The most prevalent resistance mechanism detected was the AmpC β-lactamase gene blaCMY.Other β-lactamase genes detected included 11 blaTEM-1, 3 blaPSE-1, 2 blaOXA-1, and 1 blaCTX-M-15. The ceftriaxone MIC values for the blaCMY-containing isolates ranged from 4 to 64 mg/L; all blaCMY-bearing isolates were classified as ceftriaxone resistant according to current CLSI guidelines.Conclusions:Among NTS isolates submitted to NARMS in 2005 and 2006, cephamycinase β-lactamases are the predominant cause of decreased susceptibility to ceftriaxone. The fact that all blaCMY-containing isolates were classified as resistant to ceftriaxone (MIC ≥4 mg/L) supports the newly revised CLSI breakpoints for cephalosporins and Enterobacteriaceae.
Published: 2010
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18. Multiple-Input Multiple-Output Model Predictive Control of a Diesel Engine

Author: Karlsson, Maria, Ekholm, Kent, Strandh, Petter, Johansson, Rolf, and Tunestål, Per
Abstract: Traditionally, diesel engine control has had to rely on indirect feedback variables and empirical open-loop maps because direct measurements of the variables representing high-level objectives, such as emissions, have not been available in production engines. With new sensors being developed, the opportunity opens to design the controller directly based on high-level objectives. In this paper, we propose to use model predictive control as a systematic way to go directly from high-level specifications to a control algorithm. The controller uses four actuator variables and five measured variables and is based on a model obtained through system identification. Experimental results on a six-cylinder heavy-duty engine around a fixed operating point demonstrate the potential of the control scheme.
Published: 2010
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19. Babesiaspecies in questing Ixodes ricinus, Sweden

Author: Karlsson, Maria E. and Andersson, Martin O.
Abstract: Babesiosis is an emerging tick-transmitted zoonosis in large parts of the world. In Sweden, the occurrence and diversity of Babesiaspecies is largely unknown. In order to estimate the exposure to Babesiafrom infected ticks, we collected questing Ixodes ricinusfrom several sites across southern Sweden during two consecutive field seasons and investigated the occurrence of Babesiaspecies. We report for the first time the occurrence of the zoonotic species Babesia venatorumin Swedish ticks, with a prevalence of 1%.We also detected B. microti(prevalence 3.2%) and B. divergens(prevalence 0.2%). The incidence of Babesiain questing ticks is substantially lower than that of several other tick-borne diseases in Sweden. Nevertheless, babesiosis should not be neglected as a possible diagnosis following tick bites in humans and animals in Sweden.
Published: 2016
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20. A semiparametric regression estimator under left truncation and right censoring

Author: Karlsson, Maria and Laitila, Thomas
Subjects: *ECONOMETRICS, *REGRESSION analysis, *MULTIVARIATE analysis, *STATISTICS
Abstract: Abstract: An estimator is proposed for semiparametric linear regression models with left truncated and right censored dependent variables. The estimator is derived from a moment condition following the principles of Newey [Newey, W.K., 2001. Conditional moment restrictions in censored and truncated regression models. Econometric Theory 17, 863–888] on conditional moment conditions. Consistency of the estimator is shown and simulation is used for illustration of the small sample properties. [Copyright &y& Elsevier]
Published: 2008
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21. Molecular Landscape of Carbapenemase-Producing Acinetobacter baumaniiin the United States

Author: Burrell, Kellan, Huang, Jennifer, Karlsson, Maria, McAllister, Gillian, and Brown, Allison
Abstract: Background:Carbapenem-resistant Acinetobacter baumannii(CRAB) are an urgent public health threat because they cause healthcare-associated infections that are difficult to treat and can spread in healthcare environments. Acinetobacterspp may develop resistance to carbapenems through various mechanisms, including decreased permeability, overexpression of efflux pumps, and production of carbapenemases. Carbapenemases found in CRAB commonly belong to the group of carbapenem-hydrolyzing class D β-lactamases, which can be either intrinsic or acquired. The most clinically relevant class D enzymes are the OXA-23-like, OXA-24/40–like, and OXA-58–like because they are commonly plasmid mediated and thereby have the potential for rapid dissemination. We describe the molecular epidemiology of CRAB in the United States using a convenience sample of isolates collected from reference submissions, an isolate-based surveillance system, and the Antibiotic Resistance Laboratory Network (ARLN). Methods:Beginning in August 2017, 7 public health laboratories in the ARLN began testing CRAB isolates submitted by participating sentinel clinical laboratories across their region. Carbapenem-resistant isolates were identified by resistance to imipenem, meropenem, or doripenem. Testing included molecular detection of 4 targeted carbapenemase genes: blaKPC, blaNDM, blaVIM, and blaIMP. Participating labs reported testing results to CDC at least monthly. A separate collection of isolates from CDC reference and surveillance activities between 2013 and 2015 underwent whole-genome sequencing (WGS) to evaluate the presence of acquired carbapenemase genes, including class D OXA-variants. Results:From August 2017 through July 2019, the ARLN tested 2,368 CRAB isolates across 44 states. Only 12 (0.5%) of these harbored a bla-gene: blaKPC (n = 5), blaNDM (n = 5), blaIMP (n = 1), and blaVIM (n = 1). Of 95 reference and surveillance isolates sequenced, none harbored these targeted carbapenemases. However, 69 (73%) harbored at least 1 acquired class D OXA gene; OXA-23 was the most commonly acquired OXA variant (n = 46, 48.4%). Conclusions:Using a multipronged approach, our studies indicate that the presence of class D β-lactamases of the OXA type are common in CRAB among surveillance and reference samples that underwent WGS analysis. Other acquired carbapenemases appear to be rare. To prevent the spread of highly resistant CRAB, particularly those carrying the targeted, emerging carbapenemase genes, continued testing, and rapid infection control are necessary to improve patient safety and maintain situational awareness.Funding:NoneDisclosures:None
Published: 2020
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22. Pilot Program for Aztreonam-Avibactam Susceptibility Testing of Metallo-Beta-Lactamase-Producing Enterobacteriaceae

Author: Bhatnagar, Amelia, Malik, Sarah, Karlsson, Maria, Lonsway, David, Lutgring, Joseph, Huang, Jennifer, Gumbis, Stephanie, and Brown, Allison
Abstract: Background:Carbapenemase-producing Enterobacteriaceae (CPE) are a major public health concern because they typically display multidrug resistance and they cause hard-to-treat infections. Organisms harboring metallo-β-lactamases (MBLs) pose a critical challenge in clinical practice because they confer resistance to nearly all β-lactams, including recently approved β-lactam combination agents. A promising new β-lactam-β-lactamase inhibitor combination for treating infections caused by MBL-producing CPE is aztreonam–avibactam. Although clinical trials using aztreonam–avibactam are ongoing, clinicians can administer this combination using 2 US Food and Drug Administration (FDA)–approved drugs: aztreonam and ceftazidime–avibactam. In 2019, the Centers for Disease Control and Prevention (CDC) initiated a pilot program in the Antibiotic Resistance Laboratory Network (AR Lab Network) to address the lack of commercially available antimicrobial susceptibility tests (ASTs) for aztreonam-avibactam by performing broth microdilution (BMD) for this drug combination. We describe the isolates submitted for aztreonam-avibactam AST during the AR Lab Network pilot in 2019. Methods: The AR Lab Network regional laboratories adopted the HP D300e Digital Dispenser to create customized BMD panels for aztreonam–avibactam ASTs. To qualify for aztreonam–avibactam AST, isolates had to be an Enterobacteriaceae displaying nonsusceptibility to all tested β-lactams (including either ceftazidime-avibactam or meropenem-vaborbactam) or confirmed to harbor at least 1 MBL gene (blaVIM, blaNDM, or blaIMP). Regional laboratories confirmed carbapenemase gene(s) using a molecular method. If an MBL gene was confirmed, aztreonam-–avibactam minimum inhibitory concentrations (MICs) were reported back to submitters within 3 working days of receipt. Findings were reported to CDC using a REDCap database. Results: From March through August 2019, aztreonam–avibactam AST was requested for 32 clinical isolates across 16 states. These isolates included 15 Escherichia coli, 12 Klebsiella pneumoniae, 4 Enterobacter cloacaecomplex, and 1 Proteus mirabilis. Molecular detection identified 27 blaNDM-positive isolates, 2 blaOXA-48-like-positive isolates, and 3 blaOXA-48/blaNDM-positive isolates. Aztreonam-avibactam results were reported for 30 isolates; 5 displayed elevated aztreonam-avibactam MICs of 8/4 µg/mL (n = 4) or 16/4 µg/mL (n = 1). Results for 2 isolates were not reported because the isolates were MBL negative. Aztreonam-avibactam MICs ranged from 0.06/4 µg/mL to 16/4 µg/mL. The MIC50/MIC90 were 0.5/4 µg/mL and 8/4 µg/mL. Conclusions:In the absence of effective FDA-approved treatments and lack of available AST for novel antibiotic combinations, CDC’s provision of AST for aztreonam-avibactam among MBL-producing CPE, offered through the AR Lab Network, helps fill a critical gap to inform patient treatment decisions. To date, our in vitro data suggest that aztreonam–avibactam could be a promising drug combination for use against infections caused by MBL-producing Enterobacteriaceae.Funding:NoneDisclosures:None
Published: 2020
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23. Whole-Genome Sequencing Reveals Diversity of Carbapenem-Resistant Pseudomonas aeruginosaCollected Through the Emerging Infections Program

Author: Stanton, Richard, Daniels, Jonathan, Breaker, Erin, Campbell, Davina, Lutgring, Joseph, Karlsson, Maria, Schutz, Kyle, Jacob, Jesse, Wilson, Lucy, Vaeth, Elisabeth, Li, Linda, Lynfield, Ruth, Phipps, Erin C., Hancock, Emily, Dumyati, Ghinwa, Tsay, Rebecca, Cassidy, P. Maureen, Mounsey, Jacquelyn, Grass, Julian, Walters, Maroya, and Halpin, Alison
Abstract: Background:Carbapenem-resistant Pseudomonas aeruginosa(CRPA) is a frequent cause of healthcare-associated infections (HAIs). The CDC Emerging Infections Program (EIP) conducted population and laboratory-based surveillance of CRPA in selected areas in 8 states from August 1, 2016, through July 31, 2018. We aimed to describe the molecular epidemiology and mechanisms of resistance of CRPA isolates collected through this surveillance. Methods:We defined a case as the first isolate of P. aeruginosaresistant to imipenem, meropenem, or doripenem from the lower respiratory tract, urine, wounds, or normally sterile sites identified from a resident of the EIP catchment area in a 30-day period; EIP sites submitted a systematic random sample of isolates to CDC for further characterization. Of 1,021 CRPA clinical isolates submitted, 707 have been sequenced to date using an Illumina MiSeq. Sequenced genomes were classified using the 7-gene multilocus sequence typing (MLST) scheme, and a core genome MLST (cgMLST) scheme was used to determine phylogeny. Antimicrobial resistance genes were identified using publicly available databases, and chromosomal mechanisms of carbapenem resistance were determined using previously validated genetic markers. Results:There were 189 sequence types (STs) among the 707 sequenced genomes (Fig. 1). The most frequently occurring were high-risk clones ST235 (8.5%) and ST298 (4.7%), which were found across all EIP sites. Carbapenemase genes were identified in 5 (<1%) isolates. Overall, 95.6% of the isolates had chromosomal mutations associated with carbapenem resistance: 93.2% had porinD-associated mutations that decrease membrane permeability to the drugs; 24.8% had mutations associated with overexpression of the multidrug efflux pump MexAB-OprM; and 22.9% had mutations associated with overexpression of the endogenous β-lactamase ampC. More than 1 such chromosomal resistance mutation type was present in 37.8% of the isolates. Conclusions:The diversity of the sequence types demonstrates that HAIs caused by CRPA can arise from a variety of strains and that high-risk clones are broadly disseminated across the EIP sites but are a minority of CRPA strains overall. Carbapenem resistance in P. aeruginosawas predominantly driven by chromosomal mutations rather than acquired mechanisms (ie, carbapenemases). The diversity of the CRPA isolates and the lack of carbapenemase genes suggest that this ubiquitous pathogen can readily evolve chromosomal resistance mechanisms, but unlike carbapenemases, these cannot be easily spread through horizontal transfer.Funding:NoneDisclosures:None
Published: 2020
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24. Molecular Epidemiology and Outcomes of Patients with Carbapenem-Resistant Enterobacteriaceae Bacteriuria, Atlanta 2012–2015

Author: Howard-Anderson, Jessica, Petit, Robert, Bower, Chris, Smith, Gillian, Ansari, Uzma, Halpin, Alison, Karlsson, Maria, Lawson, Adrian, Lutgring, Joseph, McAllister, Gillian, Farley, Monica, Jacob, Jesse, and Satola, Sarah
Abstract: Background:Carbapenem-resistant Enterobacteriaceae(CRE) represent a significant antibiotic resistance threat, in part because carbapenemase genes can spread on mobile genetic elements. Here, we describe the molecular epidemiology and outcomes of patients with CRE bacteriuria from the same city in a nonoutbreak setting. Methods: The Georgia Emerging Infections Program performs active, population-based CRE surveillance in Atlanta. We studied a cohort of patients with CRE (resistant to all tested third-generation cephalosporins and ≥1 carbapenem, excluding ertapenem) first identified in urine, and not in a prior or simultaneous sterile site, between 2012 and 2015. Whole-genome sequencing (WGS) was performed on a convenience sample. We obtained epidemiologic and outcome data through chart review and Georgia Vital Statistics records (90-day mortality). Using WGS, we created a core-genome alignment-based phylogenetic tree of the Klebsiella pneumoniaeisolates and calculated the SNP difference between each sample. Using SAS version 9.4 software, we performed the Fisher exact test and univariable odds ratios (OR) with 95% CI to compare patient isolates with and without a carbapenemase gene. Results:Among 81 patients included, the median age was 68 (IQR, 57–74) years, and most were female (58%), black (60%), and resided in a long-term care facility 4 days prior to culture isolation (53%). Organisms isolated were K. pneumoniae(84%), Escherichia coli(7%), Enterobacter cloacae(7%), and Klebsiella oxytoca(1%). WGS identified at least 1 β-lactamase gene in 91% of the isolates; 85% contained a carbapenemase gene, the most frequent of which was blaKPC-3 (94%). Patients with CRE containing a carbapenemase gene were more likely to be black (OR, 3.7; 95% CI, 1.0–13.8) and to have K. pneumoniae(OR, 8.9; 95% CI, 2.2–35.0). Using a core-genome alignment of 3,708 genes (~63% of the complete genome), we identified a median of 67 (IQR, 23–3,881) SNP differences between each K. pneumoniaeisolate. A phylogenetic tree identified clustering around carbapenemase gene and multilocus sequence type (84% were ST 258) but not based on referring laboratory or county of residence (Fig. 1). Although 7% of patients developed an invasive CRE infection within 1 year and 21% died within 90 days, having a carbapenemase gene was not associated with these outcomes. Conclusions:Molecular sequencing of a convenience sample of CRE bacteriuria support K. pneumoniaeST258 harboring blaKPC-3 being distributed throughout the Atlanta area, across the healthcare continuum. Overall mortality was high in this population, but the presence of carbapenemase genes was not associated with worse outcomes.Funding:NoneDisclosures:NoneDisclosures: NoneFunding:None
Published: 2020
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25. Estimators of Regression Parameters for Truncated and Censored Data

Author: Karlsson, Maria
Abstract: Estimators of parameters in semi-parametric left truncated and right censored regression models are proposed. In contrast to the majority of existing estimators, the proposed estimators do not require the error term of the regression model to have a symmetric distribution. In addition the estimators use asymmetric “trimming” of observations. Consistency and asymptotic normality of the estimators are shown. Finite sample properties are considered in a small simulation study. For the left truncated case, an empirical application illustrates the usefulness of the estimator.Estimators of parameters in semi-parametric left truncated and right censored regression models are proposed. In contrast to the majority of existing estimators, the proposed estimators do not require the error term of the regression model to have a symmetric distribution. In addition the estimators use asymmetric “trimming” of observations. Consistency and asymptotic normality of the estimators are shown. Finite sample properties are considered in a small simulation study. For the left truncated case, an empirical application illustrates the usefulness of the estimator.
Published: 2006
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26. Whole Gene Family Expression and Drought Stress Regulation of Aquaporins

Author: Alexandersson, Erik, Fraysse, Laure, Sjövall-Larsen, Sara, Gustavsson, Sofia, Fellert, Maria, Karlsson, Maria, Johanson, Urban, and Kjellbom, Per
Abstract: Since many aquaporins (AQPs) act as water channels, they are thought to play an important role in plant water relations. It is therefore of interest to study the expression patterns of AQP isoforms in order to further elucidate their involvement in plant water transport. We have monitored the expression patterns of all 35 Arabidopsis AQPs in leaves, roots and flowers by cDNA microarrays, specially designed for AQPs, and by quantitative real-time reverse transcriptase PCR (Q-RT-PCR). This showed that many AQPs are pre-dominantly expressed in either root or flower organs, whereas no AQP isoform seem to be leaf specific. Looking at the AQP subfamilies, most plasma membrane intrinsic proteins (PIPs) and some tonoplast intrinsic proteins (TIPs) have a high level of expression, while NOD26-like proteins (NIPs) are present at a much lower level. In addition, we show that PIP transcripts are generally down-regulated upon gradual drought stress in leaves, with the exception of AtPIP1;4 and AtPIP2;5, which are up-regulated. AtPIP2;6 and AtSIP1;1 are constitutively expressed and not significantly affected by the drought stress. The transcriptional down-regulation of PIP genes upon drought stress could also be observed on the protein level.
Published: 2005
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27. Temperature differences in the air layer close to a road surface

Author: Bogren, Jörgen, Gustavsson, Torbjörn, and Karlsson, Maria
Abstract: In this study, profiles of temperature and humidity (<250 cm above the road and 5 m into the surroundings) have been used to examine the development of temperature differences in the air layer close to the road. Temperature, humidity and wind profiles were measured, together with net radiation and observations of road surface state, at a test site at Road 45, Surte, Sweden. Measured temperature differences were compared with present weather, preceding weather, surface status, wind direction and other parameters thought to be important for the development of temperature differences. The results showed that large temperature differences (1–3°C between 250 cm and 10 cm above the road) occurred when there was a high risk of slipperiness caused by hoarfrost, snow or ice on the road. The temperature differences between different levels were associated with the exchange of humidity and temperature between the air layer and the road surface. The 10 cm level reflected the surface processes well. Higher levels were influenced by the surroundings because of turbulence and advection. This study emphasises the need for measurements to be taken at a height and place that reflects the processes at the road surface. Copyright © 2001 Royal Meteorological Society
Published: 2001
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28. Prediction of hoar-frost by use of a Road Weather information System

Author: Karlsson, Maria
Abstract: This study measured the amount of hoar-frost on the road surface with the help of copper plates. The amounts were compared to data collected at a station in the Road Weather information System (RWiS) together with additional measurements of the temperature and humidity profile above the road surface. The data were used to specify the weather parameters when hoar-frost forms on the road surface and relate the measured amount of hoar-frost and resulting friction to measured weather parameters. The aim was also to see whether there was an increased possibility of predicting the amount of hoar-frost with additional measurements of the temperature and humidity profiles. The results of this study confirm that the amount of hoar-frost deposited on the road surface increases with increasing average wind speed, increasing maximum difference between dew point (Td) and road surface temperature (Tr) and increased duration when Tr < Td, measured at the RWiS station. However, the difference between Td and Tr failed to indicate hoar-frost on several occasions due to the location and poor accuracy of the measuring equipment. Measurements of temperature and humidity in a profile up to 2.5 m above the road surface showed that the air layer up to 0.4 m reflected conditions at the road surface whereas the surrounding areas influenced the measurements at higher levels. A forward multiple regression performed on the data showed that measurements of temperature and humidity at lower levels improved predictions of deposition of hoar-frost on the road surface. Measurements of friction on the road surface when hoar-frost was present showed that friction decreased with increasing difference between Td and Tr and it also increased with the duration of Tr < Td. There was no correlation between the amount of hoar-frost and friction at the road surface. The friction is probably influenced not only by the amount of hoar-frost but also by the structure of the hoar-frost, which has not been determined in this study.
Published: 2001

29. 35th Annual Meeting of the European Association for the Study of Diabetes

Author: Melander, A., Olsson, J., Lindberg, G., Salzman, A., Howard, T., Stang, P., Lydick, E., Emslie-Smith, A., Boyle, D. I. R., Evans, J. M. M., Macdonald, T. M., Bain, J., Sullivan, F., Juhl, C., Pørksen, N., Sturis, J., Hollingdal, M., Pincus, S., Veldhuis, J., Dejgaard, A., Schmitz, O., Kristensen, J. S., Frandsen, K. B., Bayer, Th., Müller, P., Dunning, B. E., Paladini, S., Gutierrez, C., Deacon, R., Valentin, M., Grunberger, G., Weston, W. M., Patwardhan, R., Rappaport, E. B., Sargeant, L. A., Wareham, N. J., Khaw, K. T., Zethelius, Björn, Lithell, Hans, Hales, C. Nicholas, Berne, Christian, Lakka, H.-M., Oksanen, L., Tuomainen, T.-P., Kontula, K., Salonen, J. T., Dekker, J. M., de Boks, P., de Vegt, F., Stehouwer, C. D. A., Nijpels, G., Bouter, L. M., Heine, R. J., Bruno, G., Cavallo-Perin, P., Bargero, G., D’Errico, N., Borra, M., Macchia, G., Pagano, G., Newton, R. W., Ruta, D. A., New, J. P., Wallace, C., Roxburgh, M. A., Young, R. J., Vaughan, N. J. A., Elliott, P., Brennan, G., Devers, M., MacAlpine, R., Steinke, D., Lawson, D. H., Decallonne, B., Casteels, K., Gysemans, C., Bouillon, R., Mathieu, C., Linn, Thomas, Strate, Christine, Schneider, Kerstin, Funda, D. P., Jirsa, M., Kozáková, H., Kaas, A., Kofronová, O., Tlaskalová-Hogenová, H., Buschard, K., Wanka, H., Hartmann, A., Kuttler, B., Rasmussen, S. B., Sørensen, T. S., Markholst, H., Petersen, J. S., Karounos, D., Dyrberg, T., Mabley, J. G., Haskó, G., Szabó, C., Seissler, J., Nguyen, T. B. T., Steinbrenner, H., Scherbaum, W. A., Cipriani, R., Gabriele, A., Sensi, M., Guidobaldi, L., Pantellini, F., Cerrito, M. G., Scarpa, S., Di Mario, U., Morano, S., Ceolotto, G., Iori, E., Baritono, E., Del Prato, S., Semplicini, A., Trevisan, R., Zerbini, G., Meregalli, G., Asnaghi, V., Tentori, F., Maestroni, A., Mangili, R., Marescotti, C., Vedovato, M., Tiengo, A., Tadjieva, J., Mankovsky, B. N., Van Aken, S., Raes, A., Vande Walle, J., Matthys, D., Craen, M., Hansen, H. P., Lund, S. S., Rossing, P., Jensen, T., Parving, H.-H., Andersen, S., Tarnow, L., Hansen, B. V., Trautner, C., Haastert, B., Ennenbach, N., Willich, S., Tabák, Á. Gy., Orchard, T. J., Spranger, J., Preissner, K. T., Schatz, H., Pfeiffer, A., Cantón, A., Burgos, R., Hernández, C., Lecube, A., Mesa, J., Segura, R. M., Mateo, C., Simó, R., Fathallah, L., Greene, D. A., Obrosova, I., Gilbert, R. E., Kelly, D. J., Cox, A. J., Berka-Wilkinson, J. L., Taylor, H. R., Panagiotopoulos, S., Lee, V., Jerums, G., Cooper, M. E., Hitman, G. A., Aganna, E., Ogunkolade, W. B., Rema, M., Deepa, R., Shanthi-Rani, C. S., Barakat, K., Kumarajeewa, T. R., Cassell, P. G., McDermott, M. F., Mohan, V., Ways, K., Bursell, S., Devries, T., Woodworth, J., Alatorre, C., King, G., Aiello, L. P., Karisen, A. E., Pavlovic, D., Nielsen, K., Jensen, J., Andersen, H. U., Pociot, F., Mandrup-Poulsen, T., Eizirik, D. L., Nerup, J., Lortz, S., Tiedge, M., Lenzen, S., Lally, F. J., Bone, A. J., Darville, M. I., Ho, Y.-S., Sternesjö, J., Sandler, S., Chen, M.-C., Schuit, F., Pipeleers, D. G., Merezak, S., Hardikar, A., Hoet, J. J., Remacle, C., Reusens, B., Bréant, B., Garofano, A., Czernichow, P., Kubota, N., Terauchi, Y., Miki, H., Tamemoto, H., Yamauchi, T., Nakano, R., Komeda, K., Eto, K., Tobe, K., Kimura, S., Kadowaki, T., Ide, T., Murakami, K., Tsunoda, M., Mochizuki, T., Ozanne, S. E., Nave, B. T., Wang, C. L., Dorling, M. W., Petry, C. J., Koopmans, S. J., van der Bent, C., Que, I., Radder, J. K., Sebokova, E., Sana, A. K., Klimes, I., Ruderman, N., Morviducci, L., Pastore, L., Morelli, S., Sagratella, E., Zorretta, D., Buongiomo, A., Tamburrano, G., Giaccari, A., Martinenghi, Sabina, De Angelis, Gabriella Cusella, Ravasi, Flavio, Bifari, Francesco, Bordignon, Claudio, Falqui, Luca, Kessler, A., Dransfeld, O., Sasson, S., Tomas, E., Zorzano, A., Eckel, J., Thorsby, P., Rosenfalck, A. M., Kjems, L., Hanssen, K. F., Madsbad, S., Birkeland, K. I., Hamilton-Wessler, M., Markussen, J., Bergman, R. N., Melki, V., Hanaire-Broutin, H., Bessières-Lacombe, S., Tauber, J.-P., Home, P. D., Lindholm, A., Riis, A., Rosenstock, J., Schwartz, S., Clark, C., Edwards, M., Donley, D., Swift, P., Mortensen, H. B., Lynggaard, H., Hougaard, P., Cull, C. A., Neil, H. A. W., Frighi, V., Manley, S. E., Holman, R. R., Turner, R. C., Steiner, G., Davis, W. A., Weeraratna, T., Bruce, D. G., Davis, T. M. E., Vergès, B., Duvillard, L., Pont, F., Florentin, E., Gambert, Ph., Benko, B., Ljubić, S., Turk, Z., Granić, M., März, W., Wollschläger, H., Klein, G., Neiss, A., Wehling, M., Huxtable, S. J., Saker, P. J., Walker, M., Frayling, T. M., Levy, J. C., O’Rahilly, S., Hattersley, A. T., McCarthy, M. I., Orecchio, A., Giacchini, A., Dominici, R., Canettieri, G., Trinti, B., Zani, M., Andreoli, M., Sciacchitano, S., de Silva, A. M., Whitecross, K., Pasco, J., Kotowicz, M., Nicholson, G., Zimmet, P., Boyko, E. J., Collier, G. R., Frittitta, L., Pizzuti, A., Argiolas, A., Graci, S., Goldfine, I. D., Bozzali, M., Ercolino, T., Costanzo, B., Iacoviello, L., Tassi, V., Trischitta, V., Wauters, M., Rankinen, T., Mertens, I., Chagnon, M., Bouchard, C., Van Gaal, L., Sivenius, K., Valve, R., Hakkarainen, V., Niskanen, L., Laakso, M., Uusitupa, M., Beridze, N., Japaridze, M., Kurashvili, R., Dundua, M., Kebuladze, G., Kazakhashvili, N., Offley-Shore, B., Thomas, B., Ghebremeskel, K., Crawford, M., Lowy, C., Eriksson, Ulf J., Martin Simán, C., Wisse, Bert, Gittenberger-de Groot, Adriana C., Wentzel, P., Eriksson, U. J., Wender-Ożegowska, E., Drews, K., Biczysko, R., Bronisz, A., Rość, D., Graczykowska-Koczorowska, A., Kotschy, M., Sokup, A., Kohnert, K. D., Besch, W., Strese, J., Frick, U., Zander, E., Kemer, W., Škrha, J., Kvasnička, J., Kalvodová, B., Hilgertová, J., Schatteman, K., Goossens, F., Scharpé, S., De Leeuw, I., Hendriks, D., Legakis, I. N., Panayiotou, D., Mountokalakis, Th. D., Enderle, M. D., Beckmann, P., Balletshofer, B., Rittig, K., Maerker, E., Volk, A., Meisner, C., Jacob, S., Matthaei, S., Häring, H. U., Rett, K., Ueda, K., Nakagawa, T., Shimajiri, Y., Kokawa, M., Matsumoto, E., Sasaki, H., Sanke, T., Nanjo, K., McKinnon, Caroline M., Macfarlane, Wendy M., Docherty, Kevin, Furukawa, N., Shirotani, T., Kishikawa, H., Kaneko, K., Araki, E., Shichiri, M., Prentki, M., Roduit, R., Susini, S., Buteau, J., Ejrnæs, A. M., Andersen, N. Aa., Osterhoff, M., Möhlig, M., Ortmann, J., Bikashaghi, F., Mayer, C., Bikashagi, F., Ackermans, M. T., Pereira Arias, A. M., Bisschop, P. H. L. T., Endert, E., Sauerwein, H. P., Romijn, J. A., Gastaldelli, A., Baldi, S., Pettiti, M., Natali, A., Frascerra, S., Camastra, S., Toschi, E., Ferrannini, E., Stingl, H., Krssak, M., Bischof, M. G., Krebs, M., Fürnsinn, C., Nowotny, P., Waldhäusl, W., Roden, M., Neeft, M., Meijer, A. J., Båvenholm, P., Pigon, J., Efendic, S., Kästenbauer, T., Sauseng, S., Sokol, G., Auinger, M., Irsigler, K., Abbott, C. A., Carrington, A. L., Faragher, B., Kulkarni, J., Van Ross, E. R. E., Boulton, A. J. M., Armstrong, D. G., Hadi, S., Nguyen, H. C., Harkless, L. B., Jirkovská, A., Kasalicky, P., Hosová, J., Skibova, J., Uccioli, L., Caselli, A., Giacomozzi, C., Macellari, V., Giurato, L., Lardieri, L., Menzinger, G., Pham, H. T., Rosenblum, B. I., Lyons, T. E., Giurini, J. M., Smakowski, P., Chrzan, J. S., Habershaw, G. M., Veves, A., Foster, A. M., Bates, M., Doxford, M., Edmonds, M. E., Kecha, O., Winkler, R., Martens, H., Collette, J., Lefèbvre, P. J., Greiner, D., Geenen, V., Atlan-Gepner, C., Naspetti, M., Valéro, R., Barad, M., Lepault, F., Vialettes, B., Naquet, P., de Galan, B., Netea, M. G., Hancu, N., Smits, P., Van der Meer, J. W. M., Osterbye, T., Jørgensen, K. H., Tranum-Jensen, J., Fredman, P., Høy, M., Bokvist, K., Olsen, H. 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Larsen, S., Olsen, S., Bombonato, G., Sacerdoti, D., Chiesura-Corona, M., Marangon, A., Rudberg, S., Rasmussen, L., Bangstad, H.-J., Ösrterby, R., Sivous, G. I., Kasatkina, E. P., Demurov, L. M., Nosikov, V. V., Kotova, A. K., Kuraeva, T. L., Mishina, I. I., Gorashko, N. M., Nosicov, V. V., Petercova, V. A., Berrut, G., Alhenc-Gelas, F., Tsimaratos, M., Gerbi, A., Barone, R., Ollerton, R. L., Playle, R. A., Luzio, S. D., Evans, W. D., Burch, A., Siebenhofer, A., Meinitzer, A., Brandmaier, H., Brunner, G., Plank, J., West, P., Tindall, H., McKenna, K., Smith, D., Tormey, W., Kesson, C. M., Thompson, C. J., Penno, G., Anichini, R., Bandinelli, S., Boldrini, E., Giannarelli, R., Piazza, F., Pucci, L., Karunakaran, S., Morris, R. J., Nádas, J., Farkas, K., Daróczy, A., Péterfai, É., Svensson, M., Weigert, C., Facchin, S., Gambaro, G., Brodbeck, K., Schleicher, E., Tada, H., Nomura, K., Kuboki, K., Tsukamoto, M., Inokuchi, T., Menè, P., Pugliese, F., Iino, K., Yoshinari, M., Iwase, M., Asano, T., Sonoki, K., Wakisaka, M., Takata, Y., Ujishima, M., Del Prete, D., Anglani, F., Antonucci, F., Mauri, J. M., Vallés, M., Gutiérrez, C., Vendrell, J., Shinada, M., Akdeniz, A., Panagiotopoulos, P., Bach, L. A., Law, V. A., Lecomte, P. P., Yokota, C., Okuda, Y., Odawara, M., Yamashita, K., Yamada, N., Kawai, K., Açbay, Ö., Mazlum, A., Kural, E., Gündoğdu, S., Jensen, C., Körner, A., Eklöf, A.-Ch, Jaremko, G., Lal, M., DiBona, G., Aperia, A., Yavuz, D. G., Tuncer, M., Sargon, M., Küçükkaya, B., Ahıskalı, R., Akalın, Sema, Nohara, E., Oates, P. J., Ellery, C. A., Yonem, A., Azal, O., Cakýr, B., Erdogan, M. F., Corakcý, A., Ozdemir, I. C., Stevens, R. J., Yudkin, J. S., Webber, J., Wheeler, D. C., Taylor, K. G., Jones, S. L., Srivatsa, A., Anderson, S. G., Cruikshank, J. K., Florkowski, C. M., Scott, R. S., Graham, P. J., Moir, C. L., Flores, C., Ruggenenti, P., Dodesini, A. R., Vasile, B., Gaspari, F., Arnoldi, F., Ferrari, S., Ciocca, I., Spalluzzi, A., Remuzzi, G., Delvigne, C., Ballaux, D., Bosman, D. R., Winkler, A. S., Marsden, J., Watkins, P. J., Strutton, D., Erbey, J. R., Jacobsen, P., Rossing, K., Jensen, J. S., Mansfield, M. W., Kowalska, I., Telejko, B., Bachórzewska-Gajewska, A., Prokop, J., Kochman, W., Musiał, W., Naskręt, D., Oleksa, R., Zozulińska, D., Sowiński, J., Wierusz-Wysocka, B., Klamann, A., Jonas, M., Müller-Lung, U., Heuser, L., Launhardt, V., Valensi, P., Pariès, J., Torremocha, F., Brulport, V., Sachs, R. N., Vanzetto, G., Levy, M., Lormeau, B., Halimi, S., Perfornis, A., Boumal, D., Zimmermann, C., Bernard, Y., Sabbah, A., Meneveau, N., Gautier, S., Bassand, J. P., Anděl, M., Kraml, P., Potočková, J., Dvořáková, H., Trešlová, L., Nuttall, S. L., Martin, U., Kendall, M. J., Schiaffini, R., Pantaleo, A., Battocletti, T., Vaccari, V., Brufani, C., Martuscelli, E., Gargiulo, P., Nieszner, E., Posa, I., Kocsis, E., Préda, I., Pogatsa, G., Koltai, M. Z. S., Stefanidis, A., Manoussakis, S., Handanis, S., Zairis, M., Vitalis, D., Dadiotis, L., Fiorina, P., La Rocca, E., Astorri, E., Rossetti, C., Lucignani, G., Giudici, D., Castoldi, R., Mazarakis, N., Giagiakou, E., Karavidas, A., Agellou, A., Karamani, O., Matsakas, E., Caviezel, F., Morricone, L., Ranucci, M., Denti, S., Cazzaniga, A., Enrini, R., Isgrò, G., González de Molina, F. J., Sala, J., Masià, R., Marrugat, J., Kruszewski, P., Wolnik, B., Bieniaszewski, L., Świerblewska, E., Semetkowska-Jurkiewicz, E., Krupa-Wojciechowska, B., Vasilikos, P. G., Alaveras, A. E. G., Anastasopoulos, N. G., Chala, E., Sidira, M., Christakopoulos, P. D., Poulsen, P. L., Hansen, K. W., Ebbehøj, E., Knudsen, S. T., Mogensen, C. E., Ramu, Y., Vidyullatha, Y., Strojek, K., Gorska, J., Morawin, E., Ritz, E., Ciavarella, A., Malini, P. L., Strocchi, E., Fiumi, N., Ambrosioni, E., Idzior-Waluś, B., Stevens, L., McEneny, J., O’Kane, M. J., Moles, K. W., McMaster, C., Young, I. S., Leonhardt, W., Konstadelou, E., Gürlek, Alper, Soedamah-Muthu, S., Taskinen, M. R., Ehnholm, C., Wägner, A., Bayen, Laia, Rigla, M., Ortega, E., Caixàs, A., Mestrón, A., Ordóñez, J., Pérez, A., Sotiropoulou, G., Servais, P. L., Bertolotto, A., Pilo, M., Suchánková, G., Andratschke, S., Tschöp, M., Strasburger, C.-J., Rizzo, L., Aerts, P., Vinckx, M., Ansquer, J. C., Ryan, M., Buter, H., Navis, G. J., de Jong, P. E., de Zeeuw, D., Carreras, G., Giménez, G., Pou, J. M., Howorka, K., Gabriel, M., Pumprla, J., Köves, A., Bhowmik, N. B., Haque, A., Rahman, A., Paleari, F., Gamba, P., Mauri, G., Rovaris, G., Giannattasio, C., Piatti, M. L., Zincone, A., Cavaletti, G., Mancia, G., Lan, S., Arezzo, J., Gerber, R. A., Klioze, S. S., Saponara, C., Tartaglione, T., Cercone, S., Caputo, S., Meloni, T., Brunetti, D., Di Lazzaro, V., Xu, G., Jiang, H. Y., Shy, M. E., Sugimoto, K., Zhang, W.-X., Kuchmerovskaya, T., Donchenko, G., Shymansky, I., Kuchmerovsky, N., Pakyrbaeva, L., Cameron, N. E., Keegan, A., Cotter, M. A., Mirrlees, D., Smale, S. E., Biessels, G. J., Duis, S. E. J., Kamal, A., Gispen, W. H., Carrington, A., Carman, S., Smiarowski, H., Lavoie, D., Sawicki, D., Sabetta, A., Litchfield, J., Van Zandt, M., Sredy, J., Smirnova, V., Strokov, I., Ivanova, L., Ichunina, A., Nakamura, J., Nakayama, M., Hamada, Y., Chaya, S., Kato, K., Kasuya, Y., Mizubayashi, R., Miwa, K., Yasuda, Y., Kamiya, H., Hotta, N., Bíró, K., Kukorelli, T., Szilágyi, N., Kürthy, M., Komáromy, A., Mogyorosi, T., Nagy, K., Çakir, M., Baskal, N., Güllü, S., Elhan, A. H., Erdogan, G., Ziegler, D., Piolot, R., Neubauer, J., Senesi, B., Bonetti, R., Napolitano, A., Canepa, F., Ottonello, P., Schabmann, A., Giménez-Pérez, G., Arroyo, J. A., López, T., Ponz, E., Mauricio, D., Diem, P., Zanchin, L., Suter, S. L., Lefrandt, J. D., Smit, A., van Roon, A. M., Dullaart, R., Voita, D., Mackevics, V., Vitols, A., Lengyel, Cs., Farkas, Gy., Török, T., Légrády, P., Várkonyi, T. T., Kardos, A., Gingl, Z., Kempler, P., Rudas, L., Lonovics, J., Marchand, M., Stevens, L. K., Tarnás, Gy., Estrella, F., Christensen, N. J., Keresztes, K., Barna, I., Hermányi, Zs., Vargha, P., Bonnevie, L., Chanudet, X., Larroque, P., Tutuncu, N. Bascil, Deger, A., Batur, M. K., Yildirir, A., Onalan, O., Aksöyek, S., Kabakçι, G., Erbaş, T., Galicka-Latała, D., Surdacki, A., Gerritsen, J., TenVoorde, B. J., Heethaar, R. M., Tagawa, T. S., Kodama, M., Yoshioka, R., Yamasaki, Y., Didangelos, T., Athyros, V., Kontopoulos, A., Papageorgiou, A., Karamitsos, D., Lacigová, S., Rušavý, Z., Kárová, R., Perrild, H., Kay, L., Jørgensen, T., Bień, A. I., Witek, P., Geraldes, Elizabete, Rodrigues, D., Pereira, L., Doménech, A., Leitão, P., Anagnostopoulos, D., Foster, A. V. M., Nag, S., Barsoum, M., Lewis, G., Dunlop, N., Connolly, V., Bilous, R., Kelly, W., Chantelau, E., Gede, A., Sharman, D., O’Halloran, D., Best, C., Abbas, Z. G., Lutale, J., Gill, G. V., Jarvis, W. R., Archibald, L. K., Corcoran, S., Mansell, J., Pibworth, L., Terada, H., Shiba, T., Utugi, N., Utugi, T., Blum, M., Strobel, J., Höffken, K., Razvi, F. M., Kritzinger, E. E., Taylor, K., Jones, S., Illahi, W., Grüβer, M., Hartmann, P., Hoffstadt, K., van Leiden, H. A., Moll, A. C., Polak, B. C. P., Pietragalla, G. B., Maurino, M., Montanaro, M., Karadeniz, Ş., Tommasini, P., Quadrini, C., Demiraj, V., Rispoli, E., Ota, A., Takama, H., Saito, N., Hemández, C., Lepore, D., Antico, L., Giardina, B., Franconi, F., Michoud, E., Chamot, S., Riva, Ch., Hammes, H.-P., Renner, O., Breier, G., Lin, J., Alt, A., Betzholtz, C., Bretzel, R. G., Manti, R., Gallo, M., Molinar Hin, A., Brignardello, E., Boccuzzi, G., Li, Shanfang, Xiang, Kunsan, Zhang, Rugeng, Shangguan, Xinhong, Wu, Jianrong, Donnan, P. T., Broomhall, J., Hunter, K., Morris, A. D., Ioannidis, G., Peppa, M., Rontogianni, E., Kallifronas, M., Lekatsas, I., Chrysanthopoulou, G., Anthopoulos, L., Kesse, M., Thalassinos, N., Neves, C., Medina, J. L., Lopes, F., Yılmaz, M., Güvener, N., Güvener, M., Kocagöz, T., Böke, E., Paşaoglu, I., Bascil Tutuncu, N., Oto, A., Karvonen, M. K., Koulu, M., Pesonen, U., Mercuri, M., Rauramaa, R., Rutter, M. K., Kestevan, P., McComb, J. M., Marshall, S. M., Sobieska, M., Wiktorowicz, K., Kanters, S. D. J. M., Banga, J. D., Algra, A., Frijns, C. J. M., Beutler, J. J., Fijnheer, R., Nicoloff, G., Baydanoff, S., Stanimirova, N., Petrova, Ch., Lario, S., Campistol, J. M., Cases, A., Clària, J., Iñigo, P., Esmatjcs, E., Sármán, B., Tóth, M., Kocsis, I., Somogyi, A., Bumbure, A., Jachimowicz, K., Samson, J., Tomasiak, M., Sobol, A., Stańczyk, L., Watala, C., Stradina, P., Wiśniewska-Jarosińska, M., Marciniak, D., Więcławska, B., Watała, C., Golański, J., Zinnat, R., Mahmud, I., Büyükasik, Yahya, Demiroğlu, H., Szczepanik, A., Skowroński, M., Murawska, A., Meeking, D. R., Allard, S., Munday, J., Chowienczyk, P., Shaw, K. M., Cummings, M. H., Šimková, R., Jirsa, M., Hadoke, P. W. F., McIntyre, C. A., Jones, G. C., Williams, B. C., Elliott, A. I., McKnight, J. A., Pernow, J., Bombonato, G. C., Finucci, G. F., Zotta, L., Senses, V., Ozyazgan, S., Ince, E., Tunçdemir, M., Oztürk, M., Sultuybek, G., Akkan, A. G., Özyazgan, S., Unlücerci, Y., Bekpınar, S., Meyer, M. F., Lee, B. C., Shore, A. C., Humphreys, J. M., Tooke, J. E., Dell’Omo, G., Giovannitti, G., Caricato, F., Mariani, M., Pedrinelli, R., Kiviet-Boehm, C., Schwelling, V., Matthäei, S., Pfohl, M., McInerney, D., Itoh, H., Ohno, T., Katoh, N., Baumgartner-Parzer, S., Artwohl, M., Graier, W., Ludwig, C., Tachi, Y., Bannai, C., Shinohara, M., Shimpuku, H., Ohura, K., Bertacca, A., Sasvári, M., Szaleczki, E., Pusztai, P., Boes, U., Klaus, E., Dittrich, P., Wagner, Z., Wittmann, I., Pótó, L., Wagner, L., Mazák, I., Nagy, J., Feletto, F., Taboga, C., Tonutti, L., Lizzio, S., Russo, A., Selmo, V., Ceriello, A., Lekakis, J., Papamichael, C. M., Stamatelopoulos, K., Stamatelopoulos, S., Yillar, D. O., Gay, M., Lillaz, E., Passaro, A., Vanini, A., Calzoni, F., D’Elia, K., Carantoni, M., Zuliani, G., Fellin, R., Solini, A., Chwatko, G., Bald, E., Dramais, A.-S., Wallemacq, P. E., Vandeleene, B., Ciaria, M. V., Ariano, M., Strom, R., Gibney, J., Weiss, U., Turner, B., O’Gorman, P., Watts, G., Powrie, J., Crook, M., Shaw, K., and Cummings, M.
Published: 1999
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30. Mortality Trends for Leukemia in Selected Countries

Author: WINGREN, GUN and KARLSSON, MARIA
Published: 1990
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31. Aztreonam-Avibactam Susceptibility Testing Program for Metallo-Beta-Lactamase-Producing Enterobacteralesin the Antibiotic Resistance Laboratory Network, March 2019 to December 2020

Author: Bhatnagar, Amelia, Boyd, Sandra, Sabour, Sarah, Bodnar, Janine, Nazarian, Elizabeth, Peinovich, Nadine, Wagner, Christine, Craft, Bradley, Snippes Vagnone, Paula, Simpson, Justin, Stone, Victoria N., Therrien, Michelle, Bateman, Allen, Lower, Danielle, Huang, Jennifer Y., Gumbis, Stephanie, Lonsway, David, Lutgring, Joseph D., Karlsson, Maria, and Brown, Allison C.
Abstract: Aztreonam-avibactam is a drug combination pending phase 3 clinical trials and is suggested for treatment of severe infections caused by metallo-beta-lactamase (MBL)-producing Enterobacteralesby combining ceftazidime-avibactam and aztreonam. Beginning in 2019, four Antibiotic Resistance Laboratory Network regional laboratories offered aztreonam-avibactam susceptibility testing by broth microdilution.
Published: 2021
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32. Antimicrobial Susceptibility Profiles To Predict the Presence of Carbapenemase Genes among Carbapenem-Resistant Pseudomonas aeruginosaIsolates

Author: Vallabhaneni, Snigdha, Huang, Jennifer Y., Grass, Julian E., Bhatnagar, Amelia, Sabour, Sarah, Lutgring, Joseph D., Campbell, Davina, Karlsson, Maria, Kallen, Alexander J., Nazarian, Elizabeth, Snavely, Emily A., Morris, Shannon, Wang, Chun, Lee, Rachel, Koag, Myong, Lewis, Robert, Garcia, Bobbiejean, Brown, Allison C., and Walters, Maroya Spalding
Abstract: Detection of carbapenem-resistant Pseudomonas aeruginosa(CRPA) with carbapenemase-producing (CP) genes is critical for preventing transmission. Our objective was to assess whether certain antimicrobial susceptibility testing (AST) profiles can efficiently identify CP-CRPA.
Published: 2021
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33. Emergence of Plasmid-Mediated Quinolone Resistance among Non-Typhi Salmonella entericaIsolates from Humans in the United States

Author: Sjölund-Karlsson, Maria, Folster, Jason P., Pecic, Gary, Joyce, Kevin, Medalla, Felicita, Rickert, Regan, and Whichard, Jean M.
Abstract: ABSTRACTPlasmid-mediated quinolone resistance determinants are emerging among gram-negative pathogens. Here we report results of a retrospective study investigating the prevalence of aac(6′)-Ib-cr, qepA, and qnrgenes among 19,010 human isolates of non-Typhi Salmonella entericacollected in the United States from 1996 to 2006.
Published: 2009
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34. New Approaches to Colonization Screening in Response to Emerging Antimicrobial Resistance

Author: Anderson, Karen, Karlsson, Maria, Boyd, Sandra, Reese, Natashia, Ansari, Uzma, Campbell, Davina, Bhatnagar, Amelia, Gable, Paige, Swint, Stephanie, Longo, Cynthia, Gilbert, Sarah, Spicer, Lori, Cochran, Jake, and Lonsway, David
Abstract: Background:The capacity to monitor the emergence of carbapenemase-producing organisms (CPO) is critical in limiting transmission. CPO-colonized patients can be identified by screening rectal specimens for carbapenemase genes and the Cepheid GeneXpert Carba-R (XCR), the only FDA-approved test, is limited to 5 carbapenemase genes and cannot identify the bacterial species. Objective:We describe the development and validation of culture-based methods for the detection of CPO in rectal cultures (RCs) and nonrectal cultures (NRCs) of tracheal aspirate and axilla-groin swabs. Methods:Colonization screening was performed at 3 US healthcare facilities; specimens of RC swabs and NRC ESwabs were collected. Each specimen was inoculated to a MacConkey broth enrichment tube for overnight incubation then were subcultured to MacConkey agar with meropenem and ertapenem 10 µg disks (BEMA) and CHROMagar KPC (KCHR) or CHROMagar Acinetobacter(ACHR). All media were evaluated for the presence of carbapenem-resistant organisms; suspect colonies were screened by real-time PCR for the most common carbapenemase genes. MALDI-TOF was performed for species identification. BEMA, a previously validated method, was the comparator for 52 RCs; clinical culture (CC) served as the comparator method for 66 NRCs. Select CPO-positive and -negative specimens underwent reproducibility testing. Results:Among 56 patients undergoing colonization screening, 12 (21%) carried a CPO. Only 1 patient had CPO solely from RC. Also, 6 patients had both CPO-positive RC and NRC, and 5 patients only had a CPO-positive NRC. Of the latter, 4 had a CPO-positive tracheal specimen, and 1 had a positive culture from both tracheal and axilla-groin specimens. Sensitivity of BEMA (70%) for NRC was lower than for KCHR (96%) and ACHR (88 %) for all specimens. All methods showed a specificity of 100% and reproducibility of 92%. The detected CPO included OXA-23–positive Acinetobacter baumannii, NDM-positive Escherichia coli, KPC-positive Pseudomonas aeruginosaand 4 genera of KPC-positive Enterobacteriaceae. Conclusions:The addition of nonrectal specimens and use of selective media contributed to increased sensitivity and enhanced identification of CPO-colonized patients. Positive cultures were equally distributed among the 3 specimen types. The addition of the nonrectal specimens resulted in the identification of more colonized patients. The culture-based method was successful in detecting an array of different CPOs and target genes, including genes not detected by the Carba-R assay (eg, blaOXA-23-like). Enhanced isolation and characterization of CPOs will be key in aiding epidemiologic investigations and strengthening targeted guidance for containment strategies.Funding:NoneDisclosures:We discuss the drug combination aztreonam-avibactam and acknowledge that this drug combination is not currently FDA approved.
Published: 2020
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35. Antibiotic Susceptibility of NDM-Producing EnterobacteralesCollected in the United States in 2017 and 2018

Author: Lutgring, Joseph D., Balbuena, Rocío, Reese, Natashia, Gilbert, Sarah E., Ansari, Uzma, Bhatnagar, Amelia, Boyd, Sandra, Campbell, Davina, Cochran, Jake, Haynie, Jenn, Ilutsik, Justina, Longo, Cynthia, Swint, Stephanie, Rasheed, J. Kamile, Brown, Allison C., and Karlsson, Maria
Abstract: The treatment of infections caused by carbapenem-resistant Enterobacterales, especially New Delhi metallo-β-lactamase (NDM)-producing bacteria, is challenging. Although less common in the United States than some other carbapenemase producers, NDM-producing bacteria are a public health threat due to the limited treatment options available. Here, we report on the antibiotic susceptibility of 275 contemporary NDM-producing Enterobacteralescollected from 30 U.
Published: 2020
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36. Difficult-To-Detect Staphylococcus aureus: mecA-Positive Isolates Associated with Oxacillin and Cefoxitin False-Susceptible Results

Author: Gargis, Amy S., Yoo, Brian B., Lonsway, David R., Anderson, Karen, Campbell, Davina, Ewing, Thomas O., Lawsin, Adrian, Machado, María-José, Yamamoto, Norihisa, Halpin, Alison Laufer, Lutgring, Joseph D., Karlsson, Maria, Rasheed, J. Kamile, and Elkins, Christopher A.
Published: 2020
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37. Validation of Aztreonam-Avibactam Susceptibility Testing Using Digitally Dispensed Custom Panels

Author: Ransom, Eric, Bhatnagar, Amelia, Patel, Jean B., Machado, Maria-Jose, Boyd, Sandra, Reese, Natashia, Lutgring, Joseph D., Lonsway, David, Anderson, Karen, Brown, Allison C., Elkins, Christopher A., Rasheed, J. Kamile, and Karlsson, Maria
Abstract: Aztreonam-avibactam is a combination antimicrobial agent with activity against carbapenemase-producing Enterobacteriaceae(CPE) with metallo-ß-lactamases (MßLs). Although aztreonam-avibactam is not yet approved by the U.S. Food and Drug Administration (FDA), clinicians can administer this combination by using two FDA-approved drugs: aztreonam and ceftazidime-avibactam. This combination of drugs is recommended by multiple experts for treatment of serious infections caused by MßL-producing CPE.
Published: 2020
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38. Evaluation of the MicroScan Colistin Well and Gradient Diffusion Strips for Colistin Susceptibility Testing in Enterobacteriaceae

Author: Lutgring, Joseph D., Kim, Anny, Campbell, Davina, Karlsson, Maria, Brown, Allison C., and Burd, Eileen M.
Abstract: Many laboratories are unable to perform colistin susceptibility testing. Diffusion-based antimicrobial susceptibility testing methods are not recommended, and not all laboratories have the capacity to perform broth microdilution (BMD).
Published: 2019
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39. Identification of a Carbapenemase-Producing Hypervirulent Klebsiella pneumoniaeIsolate in the United States

Author: Karlsson, Maria, Stanton, Richard A., Ansari, Uzma, McAllister, Gillian, Chan, Monica Y., Sula, Erisa, Grass, Julian E., Duffy, Nadezhda, Anacker, Melissa L., Witwer, Medora L., Rasheed, J. Kamile, Elkins, Christopher A., and Halpin, Alison Laufer
Abstract: We report on a carbapenemase-producing hypervirulent Klebsiella pneumoniae(CP-hvKP) isolate collected from a U.S. patient at an outpatient clinic.
Published: 2019
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40. Genomic Analysis of a Pan-Resistant Isolate of Klebsiella pneumoniae, United States 2016

Author: de Man, Tom J. B., Lutgring, Joseph D., Lonsway, David R., Anderson, Karen F., Kiehlbauch, Julia A., Chen, Lei, Walters, Maroya Spalding, Sjölund-Karlsson, Maria, Rasheed, J. Kamile, Kallen, Alexander, and Halpin, Alison Laufer
Abstract: ABSTRACTAntimicrobial resistance is a threat to public health globally and leads to an estimated 23,000 deaths annually in the United States alone. Here, we report the genomic characterization of an unusual Klebsiella pneumoniae, nonsusceptible to all 26 antibiotics tested, that was isolated from a U.S. patient. The isolate harbored four known beta-lactamase genes, including plasmid-mediated blaNDM-1and blaCMY-6, as well as chromosomal blaCTX-M-15and blaSHV-28, which accounted for resistance to all beta-lactams tested. In addition, sequence analysis identified mechanisms that could explain all other reported nonsusceptibility results, including nonsusceptibility to colistin, tigecycline, and chloramphenicol. Two plasmids, IncA/C2 and IncFIB, were closely related to mobile elements described previously and isolated from Gram-negative bacteria from China, Nepal, India, the United States, and Kenya, suggesting possible origins of the isolate and plasmids. This is one of the first K. pneumoniaeisolates in the United States to have been reported to the Centers for Disease Control and Prevention (CDC) as nonsusceptible to all drugs tested, including all beta-lactams, colistin, and tigecycline.IMPORTANCEAntimicrobial resistance is a major public health threat worldwide. Bacteria that are nonsusceptible or resistant to all antimicrobials available are of major concern to patients and the public because of lack of treatment options and potential for spread. A Klebsiella pneumoniaestrain that was nonsusceptible to all tested antibiotics was isolated from a U.S. patient. Mechanisms that could explain all observed phenotypic antimicrobial resistance phenotypes, including resistance to colistin and beta-lactams, were identified through whole-genome sequencing. The large variety of resistance determinants identified demonstrates the usefulness of whole-genome sequencing for detecting these genes in an outbreak response. Sequencing of isolates with rare and unusual phenotypes can provide information on how these extremely resistant isolates develop, including whether resistance is acquired on mobile elements or accumulated through chromosomal mutations. Moreover, this provides further insight into not only detecting these highly resistant organisms but also preventing their spread.
Published: 2018
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41. Shigellosis With Decreased Susceptibility to Azithromycin

Author: Heiman, Katherine E., Grass, Julian E., Sjölund-Karlsson, Maria, and Bowen, Anna
Published: 2014
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42. Outbreak of Infections Caused by Shigella sonneiwith Reduced Susceptibility to Azithromycin in the United States

Author: Sjölund Karlsson, Maria, Bowen, Anna, Reporter, Roshan, Folster, Jason P., Grass, Julian E., Howie, Rebecca L., Taylor, Julia, and Whichard, Jean M.
Published: 2012
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43. Cow's milk proteins cause similar Th1- and Th2-like immune response in both diabetic and healthy children

Author: Karlsson, Maria G.E, Garcia, Jorge, and Ludvigsson, Johnny
Published: 2000
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