Tracks of immigrant political incorporation

Models of Immigrant Political Incorporation brings together a multidisciplinary group of scholars to consider pathways by which immigrants may be incorporated into the political processes of western democracies. It builds on a rich tradition of studying immigrant incorporation, but each chapter innovates by moving beyond singular accounts of particular groups and locations toward a general causal model with the scope and breadth to apply across groups, places, and time. Models of Immigrant Political Incorporation addresses three key analytic questions: what, if anything, are the distinctive features of immigrants or immigrant groups? How broadly should one define and study politics? What are the initial premises for analyzing pathways toward incorporation; does one learn more by starting from an assumption of racialization and exclusion or from an assumption of engagement and inclusion? While all models engage with all three key analytic questions, chapters vary in their relative focus on one or another, and in the answers they provide. Most include graphical illustrations of the model, as well as extended examples applying the model to one or more immigrant populations. At a time when research on immigrant political incorporation is rapidly accumulating - and when immigrants are increasingly significant political actors in many democratic polities — this volume makes a timely and valuable intervention by pushing researchers to articulate causal dynamics, provide clear definitions and measurable concepts, and develop testable hypotheses. Furthermore, the wide array of frameworks examining how immigrants become part of a polity or are shunted aside ensure that activists and analysts alike will find useful insights. By including historians, sociologists, and political scientists, by ranging across North America and Western Europe, by addressing successful and failed incorporative efforts, this handbook offers guides for anyone seeking to develop a dynamic, unified, and supple model of immigrant political incorporation.

Clinical, genetic, and functional characterization of adrenocorticotropin receptor mutations using a novel receptor assay.

The ACTH receptor (MC2R) is expressed predominantly in the adrenal cortex, but is one of five G protein-coupled, seven-transmembrane melanocortin receptors (MCRs), all of which bind ACTH to some degree. Testing of MC2R activity is difficult because most cells express endogenous MCRs; hence, ACTH will elicit background activation of assayable reporter systems. Inactivating mutations of MC2R lead to hereditary unresponsiveness to ACTH, also known as familial glucocorticoid deficiency (FGD). These patients are usually seen in early childhood with very low cortisol concentrations, normal mineralocorticoids, hyperpigmentation, and increased bodily growth. Several MC2R mutations have been reported in FGD, but assays of the activities of these mutants are cumbersome. We saw two patients with typical clinical findings of FGD. Genetic analysis showed that patient 1 was homozygous for the mutation R137W, and patient 2 was a compound heterozygote for S74I and Y254C. We tested the activity of these mutations in OS-3 cells, which are unresponsive to ACTH but have intact downstream cAMP signal transduction. OS-3 cells transfected with a cAMP-responsive luciferase reporter plasmid (pCREluc) were unresponsive to ACTH, but cotransfection with a vector expressing human MC2R increased luciferase activity more than 40-fold. Addition of ACTH to cells cotransfected with the pCREluc reporter and wild-type MC2R activated luciferase expression with a 50% effective concentration of 5.5 x 10(-9) M ACTH, which is similar to previously reported values. By contrast, the MC2R mutant R137W had low activity, and the S74I or Y254C mutants elicited no measurable response. This assay provides excellent sensitivity in an easily assayed transient transfection system, providing a more rapid and efficient measurement of ACTH receptor activity.

Minimally Invasive Intraoperative Stiffness Measurement of Lumbar Spinal Motion Segments

OBJECTIVE: To test a new tiny-tipped intraoperative diagnostic tool that was designed to provide the surgeon with reliable stiffness data on the motion segment during microdiscectomy. A decrease in stiffness after nuclectomy and a measurable influence of muscle tension were assumed. If the influence of muscle tension on the motion segment could at least be ruled out, there should be no difference with regard to stiffness between women and men. If these criteria are met, this new intraoperative diagnostic tool could be used in further studies for objective decision-making regarding additional stabilization systems after microdiscectomy. METHODS: After evaluation of the influence of muscle relaxation during in vivo measurements with a spinal spreader between the spinous processes, 21 motion segments were investigated in 21 patients. Using a standardized protocol, including quantified muscle relaxation, spinal stiffness was measured before laminotomy and after nuclectomy. RESULTS: The decrease in stiffness after microdiscectomy was highly significant. There were no statistically significant differences between men and women. The average stiffness value before discectomy was 33.7 N/mm, and it decreased to 25.6 N/mm after discectomy. The average decrease in stiffness was 8.1 N/mm (24%). CONCLUSION: In the moderately degenerated spine, stiffness decreases significantly after microdiscectomy. Control for muscle relaxation is essential when measuring in vivo spinal stiffness. The new spinal spreader was found to provide reliable data. This spreader could be used in further studies for objective decision-making about additional stabilization systems after microdiscectomy.

Adjuvant bevacizumab-containing therapy in triple-negative breast cancer (BEATRICE): primary results of a randomised, phase 3 trial

BACKGROUND The addition of bevacizumab to chemotherapy improves progression-free survival in metastatic breast cancer and pathological complete response rates in the neoadjuvant setting. Micrometastases are dependent on angiogenesis, suggesting that patients might benefit from anti-angiogenic strategies in the adjuvant setting. We therefore assessed the addition of bevacizumab to chemotherapy in the adjuvant setting for women with triple-negative breast cancer. METHODS For this open-label, randomised phase 3 trial we recruited patients with centrally confirmed triple-negative operable primary invasive breast cancer from 360 sites in 37 countries. We randomly allocated patients aged 18 years or older (1:1 with block randomisation; stratified by nodal status, chemotherapy [with an anthracycline, taxane, or both], hormone receptor status [negative vs low], and type of surgery) to receive a minimum of four cycles of chemotherapy either alone or with bevacizumab (equivalent of 5 mg/kg every week for 1 year). The primary endpoint was invasive disease-free survival (IDFS). Efficacy analyses were based on the intention-to-treat population, safety analyses were done on all patients who received at least one dose of study drug, and plasma biomarker analyses were done on all treated patients consenting to biomarker analyses and providing a measurable baseline plasma sample. This trial is registered with ClinicalTrials.gov, number NCT00528567. FINDINGS Between Dec 3, 2007, and March 8, 2010, we randomly assigned 1290 patients to receive chemotherapy alone and 1301 to receive bevacizumab plus chemotherapy. Most patients received anthracycline-containing therapy; 1638 (63%) of the 2591 patients had node-negative disease. At the time of analysis of IDFS, median follow-up was 31·5 months (IQR 25·6-36·8) in the chemotherapy-alone group and 32·0 months (27·5-36·9) in the bevacizumab group. At the time of the primary analysis, IDFS events had been reported in 205 patients (16%) in the chemotherapy-alone group and in 188 patients (14%) in the bevacizumab group (hazard ratio [HR] in stratified log-rank analysis 0·87, 95% CI 0·72-1·07; p=0·18). 3-year IDFS was 82·7% (95% CI 80·5-85·0) with chemotherapy alone and 83·7% (81·4-86·0) with bevacizumab and chemotherapy. After 200 deaths, no difference in overall survival was noted between the groups (HR 0·84, 95% CI 0·64-1·12; p=0·23). Exploratory biomarker assessment suggests that patients with high pre-treatment plasma VEGFR-2 might benefit from the addition of bevacizumab (Cox interaction test p=0·029). Use of bevacizumab versus chemotherapy alone was associated with increased incidences of grade 3 or worse hypertension (154 patients [12%] vs eight patients [1%]), severe cardiac events occurring at any point during the 18-month safety reporting period (19 [1%] vs two [<0·5%]), and treatment discontinuation (bevacizumab, chemotherapy, or both; 256 [20%] vs 30 [2%]); we recorded no increase in fatal adverse events with bevacizumab (four [<0·5%] vs three [<0·5%]). INTERPRETATION Bevacizumab cannot be recommended as adjuvant treatment in unselected patients with triple-negative breast cancer. Further follow-up is needed to assess the potential effect of bevacizumab on overall survival.

Validation of stress magnetic resonance imaging of the canine stifle joint with and without an intact cranial cruciate ligament.

OBJECTIVE To validate use of stress MRI for evaluation of stifle joints of dogs with an intact or deficient cranial cruciate ligament (CrCL). SAMPLE 10 cadaveric stifle joints from 10 dogs. PROCEDURES A custom-made limb-holding device and a pulley system linked to a paw plate were used to apply axial compression across the stifle joint and induce cranial tibial translation with the joint in various degrees of flexion. By use of sagittal proton density-weighted MRI, CrCL-intact and deficient stifle joints were evaluated under conditions of loading stress simulating the tibial compression test or the cranial drawer test. Medial and lateral femorotibial subluxation following CrCL transection measured under a simulated tibial compression test and a cranial drawer test were compared. RESULTS By use of tibial compression test MRI, the mean ± SD cranial tibial translations in the medial and lateral compartments were 9.6 ± 3.7 mm and 10 ± 4.1 mm, respectively. By use of cranial drawer test MRI, the mean ± SD cranial tibial translations in the medial and lateral compartments were 8.3 ± 3.3 mm and 9.5 ± 3.5 mm, respectively. No significant difference in femorotibial subluxation was found between stress MRI techniques. Femorotibial subluxation elicited by use of the cranial drawer test was greater in the lateral than in the medial compartment. CONCLUSIONS AND CLINICAL RELEVANCE Both stress techniques induced stifle joint subluxation following CrCL transection that was measurable by use of MRI, suggesting that both methods may be further evaluated for clinical use.

Cardiopulmonary performance testing using a robotics-assisted tilt table: Feasibility assessment in able-bodied subjects

BACKGROUND: Robotics-assisted tilt table technology was introduced for early rehabilitation of neurological patients. It provides cyclical stepping movement and physiological loading of the legs. The aim of the present study was to assess the feasibility of this type of device for peak cardiopulmonary performance testing using able-bodied subjects. METHODS: A robotics-assisted tilt table was augmented with force sensors in the thigh cuffs and a work rate estimation algorithm. A custom visual feedback system was employed to guide the subjects' work rate and to provide real time feedback of actual work rate. Feasibility assessment focused on: (i) implementation (technical feasibility), and (ii) responsiveness (was there a measurable, high-level cardiopulmonary reaction?). For responsiveness testing, each subject carried out an incremental exercise test to the limit of functional capacity with a work rate increment of 5 W/min in female subjects and 8 W/min in males. RESULTS: 11 able-bodied subjects were included (9 male, 2 female; age 29.6 ± 7.1 years: mean ± SD). Resting oxygen uptake (O_{2}) was 4.6 ± 0.7 mL/min/kg and O_{2}peak was 32.4 ± 5.1 mL/min/kg; this mean O_{2}peak was 81.1% of the predicted peak value for cycle ergometry. Peak heart rate (HRpeak) was 177.5 ± 9.7 beats/min; all subjects reached at least 85% of their predicted HRpeak value. Respiratory exchange ratio (RER) at O_{2}peak was 1.02 ± 0.07. Peak work rate) was 61.3 ± 15.1 W. All subjects reported a Borg CR10 value for exertion and leg fatigue of 7 or more. CONCLUSIONS: The robotics-assisted tilt table is deemed feasible for peak cardiopulmonary performance testing: the approach was found to be technically implementable and substantial cardiopulmonary responses were observed. Further testing in neurologically-impaired subjects is warranted.

Effects of stimulus with proinflammatory mediators on nitric oxide production and matrix metalloproteinase activity in explants of cranial cruciate ligaments obtained from dogs

OBJECTIVE To evaluate the origin and degree of activity of nitric oxide (NO) and matrix metalloproteinase (MMP) in explants of cranial cruciate ligaments (CCLs) obtained from dogs and cultured with and without inflammatory activators. SAMPLE POPULATION Tissue specimens obtained from 7 healthy adult Beagles that were (mean +/- SD) 4.5 +/- 0.5 years old and weighed 12.5 +/- 0.8 kg. PROCEDURE The CCLs were harvested immediately after dogs were euthanatized, and specimens were submitted for explant culture. Cultures were stimulated by incubation with a combination of interleukin-1, tumor necrosis factor-alpha, and lipopolysaccharide, or they were not stimulated. Culture supernatants were examined for production of NO nitrite-nitrate metabolites (NOts) and activity of MMP Cultured specimens were evaluated by use of immunohistochemical analysis to detect activity of inducible NO synthase (iNOS). RESULTS All ligament explants produced measurable amounts of NOts. Stimulated cultures produced significantly more NOts after incubation for 24 and 48 hours, compared with nonstimulated cultures. Production of MMP in supernatants after incubation for 48 hours was significantly higher in stimulated cultures than in nonstimulated cultures. Cells with positive staining for iNOS were detected on all slides. Positively stained cells were predominantly chondroid metaplastic. There was a significant difference in intensity of cell staining between stimulated and non-stimulated cultures. CONCLUSIONS AND CLINICAL RELEVANCE Explant cultures of intact CCLs obtained from dogs produce iNOS-induced NO. Stimulation of chondroid metaplastic cells in CCL of dogs by use of inflammatory activators can increase production of iNOS, NOts, and MMP.

The impact of loupes and microscopes on vision in endodontics.

AIM To report on an intraradicular visual test in a simulated clinical setting under different optical conditions. METHODOLOGY Miniaturized visual tests with E-optotypes (bar distance from 0.01 to 0.05 mm) were fixed inside the root canal system of an extracted maxillary molar at different locations: at the orifice, a depth of 5 mm and the apex. The tooth was mounted in a phantom head for a simulated clinical setting. Unaided vision was compared with Galilean loupes (2.5× magnification) with integrated light source and an operating microscope (6× magnification). The influence of the dentists' age within two groups was evaluated: <40 years (n = 9) and ≥40 years (n = 15). RESULTS Some younger dentists were able to identify the E-optotypes at the orifice, but otherwise, natural vision did not reveal any measurable result. With Galilean loupes, the younger dentists <40 years could see a 0.05 mm structure at the root canal orifice, in contrast to the older group ≥40 years. Only the microscope allowed the observation of structures inside the root canal, independent of age. CONCLUSION Unaided vision and Galilean loupes with an integrated light source could not provide any measurable vision inside the root canal, but younger dentists <40 years could detect with Galilean loupes a canal orifice corresponding to the tip of the smallest endodontic instruments. Dentists over 40 years of age were dependent on the microscope to inspect the root canal system.

Late onset and pregnancy-induced congenital thrombotic thrombocytopenic purpura.

UNLABELLED We report on our patient (case 2) who experienced a first acute episode of thrombotic thrombocytopenic purpura (TTP) at the age of 19 years during her first pregnancy in 1976 which ended in a spontaneous abortion in the 30th gestational week. Treatment with red blood cell concentrates was implemented and splenectomy was performed. After having suffered from several TTP episodes in 1977, possibly mitigated by acetylsalicylic acid therapy, an interruption and sterilization were performed in 1980 in her second pregnancy thereby avoiding another disease flare-up. Her elder sister (case 1) had been diagnosed with TTP in 1974, also during her first pregnancy. She died in 1977 during her second pregnancy from a second acute TTP episode. DIAGNOSIS In 2013 a severe ADAMTS13 deficiency of <10% without detectable ADAMTS13 inhibitor was repeatedly found. Investigation of the ADAMTS13 gene showed that the severe ADAMTS13 deficiency was caused by compound heterozygous ADAMTS13 mutations: a premature stop codon in exon 2 (p.Q44X), and a missense mutation in exon 24 (p.R1060W) associated with low but measurable ADAMTS13 activity. CONCLUSION Genetic analysis of the ADAMTS13 gene is important in TTP patients of all ages if an ADAMTS13 inhibitor has been excluded.

Kinetics and kinematics of the tölt: effects of rider interaction and shoeing manipulations

Introduction . Compared to most equine horse breeds which are able to walk, trot and canter /gallop, the gait repertoire of the Icelandic horses additionally includes the lateral gait tölt and frequently also the pace. With respect to the tölt gait, special shoeing, saddling and riding techniques have been developed for Icelandic horses in order to enhance its expressiveness and regularity. Toes are left unnaturally long and heavy shoes and paddings, as well as weighted boots are used to enforce the individual gait predisposition. For the same reason, the rider is placed more caudally to the horse's centre of mass as compared to other riding techniques. The biomechanical impact of these methods on the health of the locomotor system has so far never been subject of systematic research. Objectives . The aims of the presented study are (1) to describe the kinetic and kinematic characteristics of the tölt performed on a treadmill, (2) to understand the mechanical consequences of shoeing manipulation (long hooves, weighted boots) on the loading and protraction movement of the limbs, as well as (3) to study the pressure distribution and effects on the gait pattern of 3 different saddle types used for riding Icelandic horses. Materials and methods . Gait analysis was carried out in 13 Icelandic horses at walk and at slow and medium tölting and trotting speeds on a high-speed treadmill instrumented for measuring vertical ground reaction forces as well as temporal and spatial gait variables. Kinematic data of horse, rider and saddle were measured simultaneously. Gait analysis was first carried out with high, long hooves (SH) without and in combination with weighted boots (ad aim (2)). Afterwards, horses were re-shod according to current horseshoeing standards (SN) and gait analysis was repeated (ad aims (1) and (2)). In a second trial, horses were additionally equipped with a pressure sensitive saddle mat and were ridden with a dressage-like saddle (SDres), an Icelandic saddle (Slcel) and a saddle cushion (SCush) in the standard saddle position (ad aim 3). Results and conclusions . Compared to trot at the same speed, tölting horses had a higher stride rate and lower stride impulses. At the tölt loading of the forelimbs was increased in form of higher peak vertical forces (Fzpeak) due to shorter relative stance durations (StDrel). Conversely, in the hindlimbs, longer StDrel resulted in lower Fzpeak. Despite the higher head-neck position at tölt, there was no measurable shift in weight to the hindlimbs. Footfall rhythm was in most horses laterally coupled at the tölt and frequently had a slight fourbeat and a very short suspension phase at trot; underlining the fact that performance of correct gaits in Icelandic horses needs special training. Gait performance as it is currently judged in competition could be improved using a shoeing with SH, resulting in a 21 ± 5 mm longer dorsal hoof wall, but also a weight gain of 273 ± 50 g at the distal limb due to heavier shoeing material. Compared to SN, SH led to a lower stride rate, a longer stride length and a higher, but not wider, forelimb protraction arc, which were also positively associated with speed. At the tölt, the footfall rhythm showed less tendency to lateral couplets and at the trot, the suspension phase was longer. However, on the long term, SH may have negative implications for the health of the palmar structures of the distal foot by increased limb impulses, higher torques at breakover (up to 20%); as well as peak vertical forces at faster speeds. Compared to the shoeing style, the saddle type had less influence on limb forces or movements. The slight weight shift to the rear with SCush and Slcel may be explained by the more caudal position of the rider relative to the horse's back. With SCush, pressure was highest under the cranial part of the saddle, whereas the saddles with trees had more pressure under the caudal area.

Relating in situ gas measurements to the surface outgassing properties of cometary nuclei

The sensitivity of the gas flow field to changes in different initial conditions has been studied for the case of a highly simplified cometary nucleus model. The nucleus model simulated a homogeneously outgassing sphere with a more active ring around an axis of symmetry. The varied initial conditions were the number density of the homogeneous region, the surface temperature, and the composition of the flow (varying amounts of H2O and CO2) from the active ring. The sensitivity analysis was performed using the Polynomial Chaos Expansion (PCE) method. Direct Simulation Monte Carlo (DSMC) was used for the flow, thereby allowing strong deviations from local thermal equilibrium. The PCE approach can be used to produce a sensitivity analysis with only four runs per modified input parameter and allows one to study and quantify non-linear responses of measurable parameters to linear changes in the input over a wide range. Hence the PCE allows one to obtain a functional relationship between the flow field properties at every point in the inner coma and the input conditions. It is for example shown that the velocity and the temperature of the background gas are not simply linear functions of the initial number density at the source. As probably expected, the main influence on the resulting flow field parameter is the corresponding initial parameter (i.e. the initial number density determines the background number density, the temperature of the surface determines the flow field temperature, etc.). However, the velocity of the flow field is also influenced by the surface temperature while the number density is not sensitive to the surface temperature at all in our model set-up. Another example is the change in the composition of the flow over the active area. Such changes can be seen in the velocity but again not in the number density. Although this study uses only a simple test case, we suggest that the approach, when applied to a real case in 3D, should assist in identifying the sensitivity of gas parameters measured in situ by, for example, the Rosetta spacecraft to the surface boundary conditions and vice versa.

Quantification of anandamide and 2-arachidonoylglycerol plasma levels to examine potential influences of tetrahydrocannabinol application on the endocannabinoid system in humans

The effects of tetrahydrocannabinol (THC) and endogenous cannabinoids (endocannabinoids, ECs) are both mediated by activation of the cannabinoid receptors CB1 and CB2. Exogenous activation of these receptors by THC could therefore alter EC levels. We tested this hypothesis in healthy volunteers (n = 25) who received a large intravenous dose of THC (0.10 mg/kg). Effects on the EC system were quantified by serial measurements of plasma ECs after THC administration. Eleven blood samples were drawn during the first 5 h after THC administration and two more samples after 24 and 48 h. THC, its metabolites THC-OH (biologically active) and THC-COOH (non-active), and the ECs anandamide and 2-arachidonoylglycerol (2-AG) were quantified by liquid chromatography-mass spectrometry. EC-plasma levels showed a biphasic response after THC injection reaching maximal values at 30 min. Anandamide increased slightly from 0.58 ± 0.21 ng/ml at baseline to 0.64 ± 0.24 ng/ml (p < 0.05) and 2-AG from 7.60 ± 4.30 ng/ml to 9.50 ± 5.90 ng/ml (p < 0.05). After reaching maximal concentrations, EC plasma levels decreased markedly to a nadir of 300 min after THC administration (to 0.32 ± 0.15 ng/ml for anandamide and to 5.50 ± 3.01 ng/ml for 2-AG, p < 0.05). EC plasma concentrations returned to near baseline levels until 48 h after the experiment. THC (0.76 ± 0.16 ng/ml) and THC-OH (0.36 ± 0.17 ng/ml) were still measurable at 24 h and remained detectible until 48 h after THC administration. Although the underlying mechanism is not clear, high doses of intravenous THC appear to influence endogenous cannabinoid concentrations and presumably EC-signalling.

An updated synthesis of the observed and projected impacts of climate change on the chemical, physical and biological processes in the oceans

The 5th Assessment Report (AR5) of the Intergovernmental Panel on Climate Change (IPCC) states with very high certainty that anthropogenic emissions have caused measurable changes in the physical ocean environment. These changes are summarized with special focus on those that are predicted to have the strongest, most direct effects on ocean biological processes; namely, ocean warming and associated phenomena (including stratification and sea level rise) as well as deoxygenation and ocean acidification. The biological effects of these changes are then discussed for microbes (including phytoplankton), plants, animals, warm and cold-water corals, and ecosystems. The IPCC AR5 highlighted several areas related to both the physical and biological processes that required further research. As a rapidly developing field, there have been many pertinent studies published since the cut off dates for the AR5, which have increased our understanding of the processes at work. This study undertook an extensive review of recently published literature to update the findings of the AR5 and provide a synthesized review on the main issues facing future oceans. The level of detail provided in the AR5 and subsequent work provided a basis for constructing projections of the state of ocean ecosystems in 2100 under two the Representative Concentration Pathways RCP4.5 and 8.5. Finally the review highlights notable additions, clarifications and points of departure from AR5 provided by subsequent studies.

Modelling the system behaviour of wet snow avalanches using an expert system approach for risk management on high alpine traffic roads

The presented approach describes a model for a rule-based expert system calculating the temporal variability of the release of wet snow avalanches, using the assumption of avalanche triggering without the loading of new snow. The knowledge base of the model is created by using investigations on the system behaviour of wet snow avalanches in the Italian Ortles Alps, and is represented by a fuzzy logic rule-base. Input parameters of the expert system are numerical and linguistic variables, measurable meteorological and topographical factors and observable characteristics of the snow cover. Output of the inference method is the quantified release disposition for wet snow avalanches. Combining topographical parameters and the spatial interpolation of the calculated release disposition a hazard index map is dynamically generated. Furthermore, the spatial and temporal variability of damage potential on roads exposed to wet snow avalanches can be quantified, expressed by the number of persons at risk. The application of the rule base to the available data in the study area generated plausible results. The study demonstrates the potential for the application of expert systems and fuzzy logic in the field of natural hazard monitoring and risk management.

In vivo Evolution of CMY-2 to CMY-33 β-Lactamase in Escherichia coli ST131: Characterization of an Acquired Extended-Spectrum AmpC (ESAC) Conferring Resistance to Cefepime.

Cefepime is frequently prescribed to treat infections caused by AmpC-producing Gram-negative bacteria. CMY-2 is the most common plasmid-mediated AmpC (pAmpC) β-lactamase. Unfortunately, CMY variants conferring enhanced cefepime resistance are reported. Here, we describe the evolution of CMY-2 to an extended-spectrum AmpC (ESAC) in clonally identical E. coli isolates obtained from a patient. The CMY-2-producing E. coli (CMY-2-Ec) was isolated from a wound. Thirty days later, one CMY-33-producing E. coli (CMY-33-Ec) was detected in bronchoalveolar lavage. Two weeks before the isolation of CMY-33-Ec, the patient received cefepime.CMY-33-Ec and CMY-2-Ec were identical by rep-PCR, being of hyperepidemic ST131, but showed different β-lactam MICs (e.g., cefepime 16 vs. ≤0.5 μg/ml). Identical CMY-2-Ec isolates were also found in a rectal swab. CMY-33 differs from CMY-2 by a Leu293-Ala294 deletion. Expressed in E. coli DH10B, both CMYs conferred resistance to ceftazidime (≥256 μg/ml), but cefepime MICs were higher for CMY-33 than CMY-2 (8 vs. 0.25 μg/ml). The kcat/Km or kinact/KI (μM(-1) s(-1)) indicated that CMY-33 possesses an ESBL-like spectrum compared to CMY-2 (cefoxitin: 0.2 vs. 0.4; ceftazidime: 0.2 vs. not measurable; cefepime: 0.2 vs. not measurable; tazobactam 0.0018 vs. 0.0009). Using molecular modeling, we show that a widened active site (∼4 Å shift) may play a significant role in enhancing cefepime hydrolysis. This is the first in vivo demonstration of a pAmpC that under cephalosporin treatment expands its substrate spectrum resembling an ESBL. The prevalence of CMY-2-Ec isolates is rapidly increasing worldwide, therefore awareness that cefepime treatment may select for resistant isolates is critical.