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1.
J Gen Intern Med ; 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38609706

ABSTRACT

BACKGROUND: The worldwide COVID-19 pandemic has initiated a change in medical education and the development of new teaching concepts has become inevitable to maintain adequate training. OBJECTIVE: This pilot study aims to compare teledidactic teaching with traditional face-to-face teaching for abdominal, thoracic, and thyroid ultrasound. DESIGN: Concurrently, a teledidactic and a face-to-face ultrasound course were held. The students completed seven 90-min modules using mobile ultrasound probes (Butterfly IQ). Each module consisted of a lecture, a demonstration of probe guidance, and independent training. PARTICIPANTS: A total of thirty medical students took part in the study and were randomly assigned to a teledidactic and a face-to-face group. MAIN MEASURES: An objective structured assessment of ultrasound skills (OSAUS) was performed as a pre-test and as the final exam and ultrasound images obtained during the exam were evaluated using the brightness mode quality ultrasound imaging examination (B-QUIET) scale. KEY RESULTS: No significant difference between the two cohorts on the OSAUS final exam was shown (p > 0.05 in all modules). There was a significant difference in the assessment of the images in the focused assessment with sonography for trauma (FAST) (p 0.015) and aorta (p 0.017) modules. Students in the teledidactic group performed better in both modules, scoring 33.59 (± 2.61) out of 44 in the module FAST (face-to-face group 30.95 (± 1.76)) and aortic images averaged 35.41 (± 2.61) points (face-to-face group 32.35 (± 3.08)). CONCLUSIONS: A teledidactic course for abdominal and thoracic ultrasound examinations is equally effective to traditional face-to-face teaching in this pilot study. Digital implementation with a portable ultrasound machine could be a great opportunity to promote ultrasound education worldwide and over great distances.

2.
Scand J Rheumatol ; 52(1): 51-59, 2023 01.
Article in English | MEDLINE | ID: mdl-34904536

ABSTRACT

OBJECTIVE: The purpose of this study was to determine the prevalence of joint, enthesis, bursa, and tendon ultrasound findings in large and medium joints of young, healthy individuals. METHOD: Ultrasound assessment of large and medium joints, bursae, tendons, and entheses was performed in healthy individuals below the age of 30 years. Participants also underwent bioelectrical impedance analysis and conducted supervised weight training to determine maximum strength. The prevalence of ultrasound findings was calculated and a binary logistic regression model was applied to evaluate factors associated with the present findings. RESULTS: Fifty-one healthy individuals (52.9% female) with a mean age of 23.7 years were included in this study. Joint effusion in at least one joint was observed in 72.6% of the individuals (n = 37) and entheseal pathology in at least one enthesis was detected in 27.5% (n = 14). A binary logistic regression model indicated a significant association between reported hours of sports activity per week and the prevalence of effusion in the knee (p = 0.017). In addition, associations were observed between entheseal pathology in at least one entheseal site and body mass index (BMI) (p = 0.015) as well as fat mass index (p = 0.026). CONCLUSION: Joint effusion in large and medium joints, as well as entheseal hyperperfusion, bursal effusion, and tendon sheath effusion, are found in healthy individuals. Hours of sports activity per week, BMI and fat mass index showed significant associations with the findings in joints and entheses.


Subject(s)
Knee Joint , Tendons , Humans , Female , Young Adult , Adult , Male , Prevalence , Tendons/diagnostic imaging , Ultrasonography , Knee Joint/diagnostic imaging , Lower Extremity
3.
Trials ; 23(1): 282, 2022 Apr 11.
Article in English | MEDLINE | ID: mdl-35410241

ABSTRACT

BACKGROUND: Diabetes self-management is a mainstay of diabetes care, but the implementation of self-management regimens into daily life is complex and often results in discouragement and distress. Modern approaches such as smartphone-based self-management applications are therefore needed to support people with diabetes. Since reimbursability would increase the availability of such digital applications to people with diabetes, we designed a study that meets all scientific and methodological requirements set by the German Digital Healthcare Act to allow reimbursement for a specific application (mySugr PRO). Here, we report the protocol of this study that aims at evaluating the efficacy of the digital self-management application with regard to patient-reported outcomes and medical benefits. METHODS/DESIGN: This multicenter, open-label, randomized, parallel-group, controlled trial will evaluate the health care effects and medical benefits of mySugr PRO. A total of 466 people with diabetes will be randomly allocated (2:1 randomization) to the interventional group (n = 311) that will use the digital self-management application during the 12-week study period or the control group (n = 155; no usage of the application). Baseline and follow-up examinations will assess diabetes distress as the primary endpoint as well as empowerment, HbA1c, blood glucose data, self-management, general well-being, and treatment satisfaction as secondary endpoints. Statistical analyses will use an intention-to-treat procedure (using multiple imputation for missing values) as well as a per-protocol approach for sensitivity analysis. DISCUSSION: To the best of our knowledge, this study will be one of the largest diabetes-specific evaluations of a digital health application supporting people with diabetes in their diabetes self-management that follow the requirements of the German Digital Healthcare Act. TRIAL REGISTRATION: German Clinical Trial Register DRKS00022923 . Registered on 22 October 2020.


Subject(s)
Diabetes Mellitus , Mobile Applications , Self-Management , Delivery of Health Care , Diabetes Mellitus/diagnosis , Diabetes Mellitus/therapy , Health Behavior , Humans , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Smartphone
4.
Z Rheumatol ; 81(6): 513-519, 2022 Aug.
Article in German | MEDLINE | ID: mdl-33852075

ABSTRACT

BACKGROUND: Hypophosphatasia (HPP) is a genetic disorder caused by one or more mutations in the alkaline phosphatase (ALP) gene, responsible for encoding tissue-specific ALP and for the mineralization process. OBJECTIVE: Identification of the prevalence of HPP in rheumatology patients. MATERIAL AND METHODS: Medical records of all adult rheumatology patients with pathologically low total ALP levels (<35 U/L) treated in the Department of Rheumatology at the Clinic of Internal Medicine III, University Hospital Bonn between January 2017 and June 2019, were retrospectively examined for clinical signs as well as for results of genetic tests for HPP. RESULTS: In 60 out of 2289 patients (2.62%) pathologically low ALP levels were detected. Of these 30 (1.31%) were found to have persistently low ALP levels. Genetic testing for ALP gene mutations was performed in 19 of these 30 patients and 7 of the 19 patients (36.84%) had HPP signs (insufficiency fractures, or bad dental status since childhood), all with pathologic ALP mutations. Of these patients 3 (15.78%) each had a history of insufficiency fracture with normal bone densitometry. Overall, 13 out of the 19 patients (68.42%) had mutations in the ALP gene. Interestingly, no association with chondrocalcinosis was detected in any of the patients. CONCLUSION: The HPP seems to be an underdiagnosed disease with a higher proportion of affected rheumatology patients. Therefore, future studies should aim to develop a diagnostic protocol in the clinical practice.


Subject(s)
Hypophosphatasia , Rheumatic Diseases , Adult , Alkaline Phosphatase/genetics , Humans , Hypophosphatasia/diagnosis , Hypophosphatasia/epidemiology , Hypophosphatasia/genetics , Mutation , Prevalence , Retrospective Studies , Rheumatic Diseases/complications
5.
Scand J Rheumatol ; 51(2): 142-151, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34229550

ABSTRACT

OBJECTIVE: To determine the prevalence of echocardiographic findings and their change over time in patients with connective tissue diseases (CTDs) and to analyse which findings were associated with escalation of immunosuppressive therapy. METHOD: We conducted a retrospective cohort study of consecutive hospitalized patients from a tertiary rheumatology referral centre who received transthoracic echocardiography between 1 January 2006 and 31 December 2015. We tested for associations between echocardiographic findings and treatment escalation via Fisher's exact test; p < 0.05 was considered significant. Escalation of therapy was defined by dosage of glucocorticoids and type of disease-modifying anti-rheumatic drug. The clinical relevance of echocardiographic findings concerning change in immunosuppressive therapy was recorded. RESULTS: In total, 1004 patients were included (865 females), with a total of 1660 echocardiographic examinations. The most frequent findings were mitral, tricuspid, and aortic valve regurgitation (found in 36.7%, 25.4%, and 17.7% of all patients), aortic valve sclerosis (20.1%), left ventricular dysfunction (21.5%), and left atrial dilatation (19.2%). Only pericardial effusions were more frequent in cases with treatment escalation (10.9% of cases with escalated therapy vs 6.9% of cases without, p = 0.007). In 314 patients who received follow-up examinations, echocardiographic findings were found to change between examinations. Only 73 of all 1660 examinations were discussed in depth considering the treatment strategy in the hospital discharge letter. CONCLUSION: Patients with CTDs exhibited a wide, dynamically changing spectrum of echocardiographic abnormalities. Most findings neither reflected disease activity nor appeared to influence the therapeutic regimen.


Subject(s)
Aortic Valve Insufficiency , Connective Tissue Diseases , Mitral Valve Insufficiency , Ventricular Dysfunction, Left , Connective Tissue Diseases/diagnostic imaging , Connective Tissue Diseases/drug therapy , Echocardiography , Female , Humans , Retrospective Studies
7.
Z Rheumatol ; 80(2): 184-188, 2021 Mar.
Article in German | MEDLINE | ID: mdl-33336292

ABSTRACT

Septic arthritis and spondylodiscitis, especially in immunocompromised patients, constitute a major differential diagnosis of joint or back pain. This results in the invasion of a joint or spinal disc and its adjacent vertebral body by a pathogen. In most cases this is manifested as unspecific symptoms, such as local joint or back pain, fever and malaise. If this is clinically suspected the bacterial infection of the joint can be confirmed by joint puncture and blood culture. For the diagnosis of spondylodiscitis magnetic resonance imaging should be used for visualization. In addition to adequate pain treatment and empirical antibiotic treatment, an arthroscopic removal of infected intra-articular tissue and debris is imperative. When complications caused by spondylodiscitis arise a surgical removal and stabilization should be performed. The following case report presents the findings of septic polyarthritis and spondylodiscitis in an immunocompromised patient with an HIV infection and provides insights into the occurrence of complications due to the delay of adequate treatment.


Subject(s)
Arthritis, Infectious , Discitis , Arthritis, Infectious/complications , Arthritis, Infectious/diagnosis , Diagnosis, Differential , Discitis/complications , Discitis/diagnosis , HIV Infections , Humans , Immunocompromised Host , Magnetic Resonance Imaging
8.
Phys Rev Lett ; 125(8): 080504, 2020 Aug 21.
Article in English | MEDLINE | ID: mdl-32909787

ABSTRACT

We implement a two-qubit logic gate between a ^{43}Ca^{+} hyperfine qubit and a ^{88}Sr^{+} Zeeman qubit. For this pair of ion species, the S-P optical transitions are close enough that a single laser of wavelength 402 nm can be used to drive the gate but sufficiently well separated to give good spectral isolation and low photon scattering errors. We characterize the gate by full randomized benchmarking, gate set tomography, and Bell state analysis. The latter method gives a fidelity of 99.8(1)%, comparable to that of the best same-species gates and consistent with known sources of error.

9.
Z Rheumatol ; 79(8): 797-808, 2020 Oct.
Article in German | MEDLINE | ID: mdl-32926217

ABSTRACT

BACKGROUND: Immune checkpoint inhibitors (ICI) have essentially improved the treatment options for various malignant diseases. They lead to an activation of the immune system and subsequent attack of tumor cells by affecting the immune system and preventing tumor cells from avoiding detection. In addition to this desired effect, immune-related adverse events (irAE) can occur in nearly all organ systems and therefore also rheumatological irAE (rh-irAE). OBJECTIVE: The occurrence of rh-irAE has been described in various publications and is specifically investigated in this review. The aim is to provide an overview on the prevalence, severity, treatment options and altered tumor response in patients with rh-irAE. MATERIAL AND METHODS: We conducted a literature search for studies and case reports on rh-irAE under ICI therapy in PubMed up to January 2020 using the PICO model. RESULTS: A total of 18 publications were included, most of which were clinical studies (n = 13) and the rest case reports (n = 5). Several rh-irAE can occur with a wide variety of manifestations of which arthralgia, arthritis and myositis were the most common. Other rheumatic diseases, such as vasculitis, connective tissue diseases and sarcoidosis were less frequently described. The published prevalence of rh-irAE varied with a prevalence between 2.3% and 6.6%. Treatment of rh-irAE depends on the severity and most patients receive nonsteroidal anti-inflammatory drugs and glucocorticosteroids. In some cases, conventional DMARDs, such as methotrexate and biological DMARDs, were administered. Patients with rh-irAE in general had a higher tumor response rate compared to patients without side effects. CONCLUSION: A close observation of patients and early detection of rh-irAE are important in order to treat these side effects in time. Further prospective studies are necessary to systematically investigate rh-irAE.


Subject(s)
Immunotherapy/adverse effects , Myositis , Rheumatic Diseases , Antibodies, Monoclonal, Humanized/adverse effects , Humans , Prevalence , Prospective Studies , Rheumatic Diseases/drug therapy , Rheumatic Diseases/epidemiology
10.
Naunyn Schmiedebergs Arch Pharmacol ; 393(9): 1573-1580, 2020 09.
Article in English | MEDLINE | ID: mdl-32377770

ABSTRACT

Omalizumab is an effective therapeutic humanized murine IgE antibody in many cases of primary systemic mast cell activation disease (MCAD). The present study should enable the clinician to recognize when treatment of MCAD with omalizumab is contraindicated because of the potential risk of severe serum sickness and to report our successful therapeutic strategy for such adverse event (AE). Our clinical observations, a review of the literature including the event reports in the FDA AE Reporting System, the European Medicines Agency Eudra-Vigilance databases (preferred search terms: omalizumab, Xolair®, and serum sickness) and information from the manufacturer's Novartis database were used. Omalizumab therapy may be more likely to cause serum sickness than previously thought. In patients with regular adrenal function, serum sickness can occur after 3 to 10 days which resolves after the antigen and circulating immune complexes are cleared. If the symptoms do not resolve within a week, injection of 20 to 40 mg of prednisolone on two consecutive days could be given. However, in MCAD patients whose adrenal cortical function is completely suppressed by exogenous glucocorticoid therapy, there is a high risk that serum sickness will be masked by the MCAD and evolve in a severe form with pronounced damage of organs and tissues, potentially leading to death. Therefore, before the application of the first omalizumab dose, it is important to ensure that the function of the adrenal cortex is not significantly limited so that any occurring type III allergy can be self-limiting.


Subject(s)
Adrenal Insufficiency/complications , Immunologic Factors/adverse effects , Mast Cells/drug effects , Mastocytosis/drug therapy , Omalizumab/adverse effects , Serum Sickness/chemically induced , Contraindications, Drug , Glucocorticoids/therapeutic use , Humans , Mast Cells/immunology , Mast Cells/metabolism , Mastocytosis/immunology , Mastocytosis/metabolism , Prednisolone/therapeutic use , Risk Assessment , Risk Factors , Serum Sickness/blood , Serum Sickness/drug therapy , Serum Sickness/immunology
11.
Rev Sci Instrum ; 90(4): 044702, 2019 Apr.
Article in English | MEDLINE | ID: mdl-31042982

ABSTRACT

Atomic physics experiments commonly use millitesla-scale magnetic fields to provide a quantization axis. As atomic transition frequencies depend on the magnitude of this field, many experiments require a stable absolute field. Most setups use electromagnets, which require a power supply stability not usually met by commercially available units. We demonstrate the stabilization of a field of 14.6 mT to 4.3 nT rms noise (0.29 ppm), compared to noise of >100 nT without any stabilization. The rms noise is measured using a field-dependent hyperfine transition in a single 43Ca+ ion held in a Paul trap at the center of the magnetic field coils. For the 43Ca+ "atomic clock" qubit transition at 14.6 mT, which depends on the field only in second order, this would yield a projected coherence time of many hours. Our system consists of a feedback loop and a feedforward circuit that control the current through the field coils and could easily be adapted to other field amplitudes, making it suitable for other applications such as neutral atom traps.

12.
Nature ; 555(7694): 75-78, 2018 02 28.
Article in English | MEDLINE | ID: mdl-29493595

ABSTRACT

Quantum bits (qubits) based on individual trapped atomic ions are a promising technology for building a quantum computer. The elementary operations necessary to do so have been achieved with the required precision for some error-correction schemes. However, the essential two-qubit logic gate that is used to generate quantum entanglement has hitherto always been performed in an adiabatic regime (in which the gate is slow compared with the characteristic motional frequencies of the ions in the trap), resulting in logic speeds of the order of 10 kilohertz. There have been numerous proposals of methods for performing gates faster than this natural 'speed limit' of the trap. Here we implement one such method, which uses amplitude-shaped laser pulses to drive the motion of the ions along trajectories designed so that the gate operation is insensitive to the optical phase of the pulses. This enables fast (megahertz-rate) quantum logic that is robust to fluctuations in the optical phase, which would otherwise be an important source of experimental error. We demonstrate entanglement generation for gate times as short as 480 nanoseconds-less than a single oscillation period of an ion in the trap and eight orders of magnitude shorter than the memory coherence time measured in similar calcium-43 hyperfine qubits. The power of the method is most evident at intermediate timescales, at which it yields a gate error more than ten times lower than can be attained using conventional techniques; for example, we achieve a 1.6-microsecond-duration gate with a fidelity of 99.8 per cent. Faster and higher-fidelity gates are possible at the cost of greater laser intensity. The method requires only a single amplitude-shaped pulse and one pair of beams derived from a continuous-wave laser. It offers the prospect of combining the unrivalled coherence properties, operation fidelities and optical connectivity of trapped-ion qubits with the submicrosecond logic speeds that are usually associated with solid-state devices.

13.
Leukemia ; 31(9): 1936-1943, 2017 09.
Article in English | MEDLINE | ID: mdl-28626218

ABSTRACT

Mutations in the epigenetic regulator gene EZH2 are frequently observed in patients with myelodysplastic/myeloproliferative neoplasms (MDS/MPN; 10-13%) and are associated with a poor outcome. To gain more insight into EZH2 pathology, we sought to genetically characterize a cohort of 41 EZH2-mutated MDS/MPN patients using targeted deep next-generation sequencing (NGS), colony-forming progenitor assays and transcriptome analysis. Stable short hairpin RNA (shRNA)-mediated downregulation of EZH2 was performed in MDS-derived F-36P, MOLM-13 and OCI-M2 cells to study EZH2-specific changes. Targeted NGS revealed a complex pattern of mutations with a total of 190 individual mutations. EZH2 mutations frequently co-occur with TET2 (58%), RUNX1 (40%) and ASXL1 (34%) mutations. Colony assays indicated EZH2 mutations to be mostly early events in leukemogenesis and showed a complex mutational hierarchy. Gene expression data revealed a number of differently expressed genes between EZH2 wild-type and mutant patients including known EZH2 targets. Comparison of patient transcriptome to EZH2-downregulated cell line data revealed several genes as novel EZH2 targets, showing opposite as well as unidirectional regulation between cell lines and patients. Some genes, such as CXXC5, ETS1 and VAV3 have previously been implied to have a role in leukemogenesis. Their precise role in MDS/MPN needs to be further investigated.


Subject(s)
Enhancer of Zeste Homolog 2 Protein/genetics , Leukemia/genetics , Mutation , Carcinogenesis/genetics , Cell Line , DNA Mutational Analysis , Gene Expression Regulation, Leukemic , High-Throughput Nucleotide Sequencing , Humans
14.
Z Rheumatol ; 76(7): 589-594, 2017 Sep.
Article in German | MEDLINE | ID: mdl-28447158

ABSTRACT

Ultrasound of the salivary glands is a specific examination for detecting pathology of salivary glands in the diagnosis of Sjögren's syndrome. It is easy to learn, rapidly performed, non-invasive and inexpensive. Other imaging techniques, such as sialography and scintigraphy, are currently only rarely performed. For the examination, linear ultrasound probes with frequencies between 7 and 12 MHz are recommended. Such probes are already widely available to the rheumatologist performing musculoskeletal ultrasound. The parotid and submandibular glands are bilaterally scanned both in longitudinal and transverse planes as a standard.Normal salivary glands have uniformly hyperechoic and homogeneous tissue. They can be clearly delineated from the surrounding muscles and soft tissue and appear similar to the thyroid gland. The salivary glands are typically hypoechoic and inhomogeneous in Sjögren's syndrome. Focal or diffuse hypoechoic or anechoic foci are found in the glands. The submandibular glands may become atrophic (sagittal diameter <8 mm). Particularly in disease flares, the parotid glands may become enlarged (sagittal diameter >20 mm). The sensitivity for the diagnosis is 60 to 90% and the specificity is over 90%.Doppler sonography does not further improve the diagnostic accuracy. Sonography has thus become an important tool in the diagnosis of Sjögren's syndrome.


Subject(s)
Sjogren's Syndrome/diagnostic imaging , Ultrasonography/methods , Humans , Parotid Gland/diagnostic imaging , Reference Values , Sensitivity and Specificity , Sjogren's Syndrome/classification , Submandibular Gland/diagnostic imaging , Thyroid Gland/diagnostic imaging
15.
Open Rheumatol J ; 10: 81-87, 2016.
Article in English | MEDLINE | ID: mdl-27867432

ABSTRACT

BACKGROUND: Rheumatoid arthritis (RA) commonly involves the knee joint in up to 30% of patients. Musculoskeletal ultrasound enables the skilled clinician to easily assess disease activity. OBJECTIVE: To evaluate the sensitivity to change of the sonography score of large joints in Rheumatology (SOLAR) for different treatments of knee arthritis in RA. METHOD: Joints were assessed by ultrasound at 4 visits. Laboratory, immunological and clinical parameters were recorded. RESULTS: 225 RA patients were analyzed. The DAS 28 in the subgroup receiving systemic steroids was significantly higher (p < 0.001) than in patients treated with intraarticular glucocorticosteroids (GCs) at T0, comparing the values from T0 to T3 the same appeared (p=0.003). Concerning the acute GC treatment regimens, the gray scale ultrasound (GSUS) sum score was found to be significantly higher in patients receiving intraarticular GCs versus no GCs (p=0,035), as well as in patients receiving systemic versus intraarticular GCs (p=0.001). Regarding the differences from T0 and T3, similar to the baseline analysis, a high GSUS sum score was significantly associated with intraarticular GCs, a low to no GC administration (p=0.035), while a high GSUS sum score was significantly linked to intraarticular GCs, rather than systemic GCs (p=0.008). CONCLUSION: SOLAR score is sensitive to change in knee arthritis. Intraarticular GC administration is performed in patients with high GSUS scores. Systemic administration of GC is linked to high disease activity (DAS28) rather than GSUS or power Doppler ultrasound (PDUS) results.

16.
Z Rheumatol ; 75(9): 939-942, 2016 Nov.
Article in German | MEDLINE | ID: mdl-27581001

ABSTRACT

Spinal epidural lipomatosis (SEL) of the thoracic and lumbar spine is a rare entity, which leads to compression of the spinal canal. The exact pathogenesis is still unknown. It most commonly occurs in patients with long-term exogenous or endogenous glucocorticoid excess or morbid obesity but there are also idiopathic forms. The symptoms depend on the severity of the SEL and can manifest as clinically asymptomatic, non-specific back pain, radiculopathy up to spinal cord compression. The diagnosis is usually achieved by magnetic resonance imaging (MRI) of the affected spinal segments. The treatment varies between discontinuation of glucocorticoids, weight reduction up to multisegmental decompressive laminectomy. The following case report presents the findings of SEL in a patient with steroid-dependent Jo-1 antibody syndrome and provides a current literature review on this rare disease.


Subject(s)
Antibodies, Antinuclear/immunology , Glucocorticoids/adverse effects , Lipomatosis/chemically induced , Lipomatosis/diagnostic imaging , Polymyositis/complications , Spinal Cord Compression/etiology , Diagnosis, Differential , Glucocorticoids/therapeutic use , Humans , Lipomatosis/prevention & control , Magnetic Resonance Imaging/methods , Male , Middle Aged , Polymyositis/diagnosis , Polymyositis/immunology , Spinal Cord Compression/diagnostic imaging , Spinal Cord Compression/prevention & control , Syndrome
17.
Nature ; 528(7582): 384-6, 2015 Dec 17.
Article in English | MEDLINE | ID: mdl-26672554

ABSTRACT

Entanglement is one of the most fundamental properties of quantum mechanics, and is the key resource for quantum information processing (QIP). Bipartite entangled states of identical particles have been generated and studied in several experiments, and post-selected or heralded entangled states involving pairs of photons, single photons and single atoms, or different nuclei in the solid state, have also been produced. Here we use a deterministic quantum logic gate to generate a 'hybrid' entangled state of two trapped-ion qubits held in different isotopes of calcium, perform full tomography of the state produced, and make a test of Bell's inequality with non-identical atoms. We use a laser-driven two-qubit gate, whose mechanism is insensitive to the qubits' energy splittings, to produce a maximally entangled state of one (40)Ca(+) qubit and one (43)Ca(+) qubit, held 3.5 micrometres apart in the same ion trap, with 99.8 ± 0.6 per cent fidelity. We test the CHSH (Clauser-Horne-Shimony-Holt) version of Bell's inequality for this novel entangled state and find that it is violated by 15 standard deviations; in this test, we close the detection loophole but not the locality loophole. Mixed-species quantum logic is a powerful technique for the construction of a quantum computer based on trapped ions, as it allows protection of memory qubits while other qubits undergo logic operations or are used as photonic interfaces to other processing units. The entangling gate mechanism used here can also be applied to qubits stored in different atomic elements; this would allow both memory and logic gate errors caused by photon scattering to be reduced below the levels required for fault-tolerant quantum error correction, which is an essential prerequisite for general-purpose quantum computing.

18.
Opt Lett ; 40(18): 4265-8, 2015 Sep 15.
Article in English | MEDLINE | ID: mdl-26371912

ABSTRACT

We demonstrate injection locking of high-power laser diodes operating at 397 nm. We achieve stable operation with an injection power of ∼100 µW and a slave laser output power of up to 110 mW. We investigate the spectral purity of the slave laser light via photon scattering experiments on a single trapped (40)Ca(+) ion. We show that it is possible to achieve a scattering rate indistinguishable from that of monochromatic light by filtering the laser light with a diffraction grating to remove amplified spontaneous emission.

19.
Leukemia ; 28(12): 2292-9, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25212276

ABSTRACT

To study clonal evolution in chronic myeloid leukemia (CML), we searched for BCR-ABL-independent gene mutations in both Philadelphia chromosome (Ph)-negative and Ph-positive clones in 29 chronic-phase CML patients by targeted deep sequencing of 25 genes frequently mutated in myeloid disorders. Ph-negative clones were analyzed in 14 patients who developed clonal cytogenetic abnormalities in Ph-negative cells during treatment with tyrosine kinase inhibitors (TKI). Mutations were detected in 6/14 patients (43%) affecting the genes DNMT3A, EZH2, RUNX1, TET2, TP53, U2AF1 and ZRSR2. In two patients, the mutations were also found in corresponding Ph-positive diagnostic samples. To further investigate Ph-positive clones, 15 randomly selected CML patients at diagnosis were analyzed. Somatic mutations additional to BCR-ABL were found in 5/15 patients (33%) affecting ASXL1, DNMT3A, RUNX1 and TET2. Analysis of individual hematopoietic colonies at diagnosis revealed that most mutations were part of the Ph-positive clone. In contrast, deep sequencing of subsequent samples during TKI treatment revealed one DNMT3A mutation in Ph-negative cells that was also present in Ph-positive cells at diagnosis, implying that the mutation preceded the BCR-ABL rearrangement. In summary, BCR-ABL-independent gene mutations were frequently found in Ph-negative and Ph-positive clones of CML patients and may be considered as important cofactors in the clonal evolution of CML.


Subject(s)
Clonal Evolution/genetics , Fusion Proteins, bcr-abl/genetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Adult , Aged , Antineoplastic Agents/therapeutic use , Chromosome Aberrations , Cohort Studies , Female , Follow-Up Studies , Fusion Proteins, bcr-abl/metabolism , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Male , Middle Aged , Mutation , Philadelphia Chromosome , Protein Kinase Inhibitors/therapeutic use
20.
Cell Death Dis ; 5: e1035, 2014 Jan 30.
Article in English | MEDLINE | ID: mdl-24481449

ABSTRACT

To combine the CD27 stimulation inhibitory effect of blocking CD70 antibodies with an antibody-dependent cellular cytotoxicity (ADCC)-independent, cell death-inducing activity for targeting of CD70-expressing tumors, we evaluated here fusion proteins of the apoptosis-inducing TNF family member TRAIL and a single-chain variable fragment (scFv) derived from a high-affinity llama-derived anti-human CD70 antibody (lαhCD70). A fusion protein of scFv:lαhCD70 with TNC-TRAIL, a stabilized form of TRAIL, showed strongly enhanced apoptosis induction upon CD70 binding and furthermore efficiently interfered with CD70-CD27 interaction. Noteworthy, introduction of recently identified mutations that discriminate between TRAILR1 and TRAILR2 binding into the TRAIL part of scFv:lαhCD70-TNC-TRAIL resulted in TRAIL death receptor-specific fusion proteins with CD70-restricted activity.


Subject(s)
CD27 Ligand/immunology , Neoplasms/drug therapy , Receptors, TNF-Related Apoptosis-Inducing Ligand/immunology , Single-Chain Antibodies/pharmacology , TNF-Related Apoptosis-Inducing Ligand/pharmacology , Apoptosis/drug effects , CD27 Ligand/genetics , Cell Line, Tumor , Humans , Mutation , Neoplasms/immunology , Neoplasms/physiopathology , Receptors, TNF-Related Apoptosis-Inducing Ligand/genetics , Single-Chain Antibodies/genetics , Single-Chain Antibodies/immunology , Species Specificity , TNF-Related Apoptosis-Inducing Ligand/genetics , TNF-Related Apoptosis-Inducing Ligand/immunology , Tumor Necrosis Factor Receptor Superfamily, Member 7/genetics , Tumor Necrosis Factor Receptor Superfamily, Member 7/immunology
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