Large-scale quantum computers will require quantum gate operations between widely separated qubits. A method for implementing such operations, known as quantum gate teleportation (QGT), requires only ...local operations, classical communication, and shared entanglement. We demonstrate QGT in a scalable architecture by deterministically teleporting a controlled-NOT (CNOT) gate between two qubits in spatially separated locations in an ion trap. The entanglement fidelity of our teleported CNOT is in the interval (0.845, 0.872) at the 95% confidence level. The implementation combines ion shuttling with individually addressed single-qubit rotations and detections, same- and mixed-species two-qubit gates, and real-time conditional operations, thereby demonstrating essential tools for scaling trapped-ion quantum computers combined in a single device.
Congophilic Fibrillary Glomerulonephritis: A Case Series Alexander, Mariam P.; Dasari, Surendra; Vrana, Julie A. ...
American journal of kidney diseases,
September 2018, 2018-09-00, 20180901, Letnik:
72, Številka:
3
Journal Article
Recenzirano
Congo Red positivity with birefringence under polarized light has traditionally permitted classification of organized glomerular deposits as from amyloid or nonamyloid diseases. The absence of ...congophilia has been used to differentiate fibrillary glomerulonephritis (GN) from amyloidosis. We describe a series of fibrillary GN cases in which the deposits are Congo Red–positive (congophilic fibrillary GN) and discuss the role of DNAJB9 in distinguishing congophilic fibrillary GN from amyloidosis.
Case series.
Analysis of the clinicopathologic characteristics of 18 cases of congophilic fibrillary GN. Mass spectrometry was performed and compared with 24 cases of Congo Red–negative fibrillary GN, 145 cases of amyloidosis, and 12 apparently healthy individuals. DNAJB9 immunohistochemistry was obtained for a subset of cases.
The proteomic signature of amyloid was not detected using mass spectrometry among cases of congophilic fibrillary GN. DNAJB9, a recently discovered proteomic marker for fibrillary GN, was detected using mass spectrometry in all cases of fibrillary GN regardless of congophilia and was absent in cases of amyloidosis and in healthy individuals. DNAJB9 immunohistochemistry confirmed the mass spectrometry findings. The congophilic fibrillary GN cases included 11 men and 7 women with a mean age at diagnosis of 65 years. Concomitant monoclonal gammopathy, hepatitis C virus infection, malignancy, or autoimmune disease was present in 35%, 22%, 17%, and 11% of patients, respectively. No patient had evidence of extrarenal amyloidosis. Patients presented with proteinuria (100%), nephrotic syndrome (47%), hematuria (78%), and chronic kidney disease (83%). After a mean follow-up of 23 months, 31% of patients progressed to end-stage kidney disease and the remaining 69% had persistently reduced kidney function.
Retrospective nature. Blinded pathology evaluations were not performed.
The congophilic properties of organized fibrillary deposits should not be solely relied on in differentiating fibrillary GN from renal amyloidosis. Mass spectrometry and DNAJB9 immunohistochemistry can be useful in making this distinction.
The clinical success of the BCL-2-selective BH3-mimetic venetoclax in patients with poor prognosis chronic lymphocytic leukemia (CLL) highlights the potential of targeting the BCL-2-regulated ...apoptotic pathway in previously untreatable lymphoid malignancies. By selectively inhibiting BCL-2, venetoclax circumvents the dose-limiting, BCL-XL-mediated thrombocytopenia of its less selective predecessor navitoclax, while enhancing efficacy in CLL. We have previously reported the potent sensitivity of many high-risk childhood acute lymphoblastic leukemia (ALL) xenografts to navitoclax. Given the superior tolerability of venetoclax, here we have investigated its efficacy in childhood ALL. We demonstrate that in contrast to the clear dependence of CLL on BCL-2 alone, effective antileukemic activity in the majority of ALL xenografts requires concurrent inhibition of both BCL-2 and BCL-XL. We identify BCL-XL expression as a key predictor of poor response to venetoclax and demonstrate that concurrent inhibition of both BCL-2 and BCL-XL results in synergistic killing in the majority of ALL xenografts. A notable exception is mixed lineage leukemia–rearranged infant ALL, where venetoclax largely recapitulates the activity of navitoclax, identifying this subgroup of patients as potential candidates for clinical trials of venetoclax in childhood ALL. Conversely, our findings provide a clear basis for progressing navitoclax into trials ahead of venetoclax in other subgroups.
•Venetoclax demonstrates potent in vitro and in vivo single-agent activity in MLL-rearranged ALL xenografts.•Clinically efficacious BH3-mimetic therapy for other high-risk ALL subtypes is likely to require concurrent BCL-2 and BCL-XL inhibition.
Autoantibodies to the M-type phospholipase A(2) receptor (PLA(2)R) are sensitive and specific for idiopathic membranous nephropathy. The anti-B cell agent rituximab is a promising therapy for this ...disease, but biomarkers of early response to treatment currently do not exist. Here, we investigated whether levels of anti-PLA(2)R correlate with the immunological activity of membranous nephropathy, potentially exhibiting a more rapid response to treatment than clinical parameters such as proteinuria. We measured the amount of anti-PLA(2)R using Western blot immunoassay in serial serum samples from a total of 35 patients treated with rituximab for membranous nephropathy in two distinct cohorts. Pretreatment samples from 25 of 35 (71%) patients contained anti-PLA(2)R, and these autoantibodies declined or disappeared in 17 (68%) of these patients within 12 months after rituximab. Those who demonstrated this immunologic response fared better clinically: 59% and 88% attained complete or partial remission by 12 and 24 months, respectively, compared with 0% and 33% among those with persistent anti-PLA(2)R levels. Changes in antibody levels preceded changes in proteinuria. One subject who relapsed during follow-up had a concomitant return of anti-PLA(2)R. In summary, measuring anti-PLA(2)R levels by immunoassay may be a method to follow and predict response to treatment with rituximab in membranous nephropathy.
Direct estimates of rare disease prevalence from public health surveillance may only be available in a few catchment areas. Understanding variation among observed prevalence can inform estimates of ...prevalence in other locations. The Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet) conducts population-based surveillance of major muscular dystrophies in selected areas of the United States. We identified sources of variation in prevalence estimates of Duchenne and Becker muscular dystrophy (DBMD) within MD STARnet from published literature and a survey of MD STARnet investigators, then developed a logic model of the relationships between the sources of variation and estimated prevalence.
The 17 identified sources of variability fell into four categories: (1) inherent in surveillance systems, (2) particular to rare diseases, (3) particular to medical-records-based surveillance, and (4) resulting from extrapolation. For the sources of uncertainty measured by MD STARnet, we estimated each source's contribution to the total variance in DBMD prevalence. Based on the logic model we fit a multivariable Poisson regression model to 96 age-site-race/ethnicity strata. Age accounted for 74% of the variation between strata, surveillance site for 6%, race/ethnicity for 3%, and 17% remained unexplained.
Variation in estimates derived from a non-random sample of states or counties may not be explained by demographic differences alone. Applying these estimates to other populations requires caution.
Abstract
We present protocols for dissipative entanglement of three trapped-ion qubits and discuss a scheme that uses sympathetic cooling as the dissipation mechanism. This scheme relies on tailored ...destructive interference to generate any one of six entangled W states in a three-ion qubit space. Using a beryllium–magnesium ion crystal as an example system, we theoretically investigate the protocol’s performance and the effects of likely error sources, including thermal secular motion of the ion crystal, calibration imperfections, and spontaneous photon scattering. We estimate that a fidelity of ∼98% may be achieved in typical trapped ion experiments with ∼1 ms interaction time. These protocols avoid timescale hierarchies for faster preparation of entangled states.
Reconstruction of a Nasal Tip Defect Morris, Lisa M; Erickson, Stephen P; Michalski, Basia M
Dermatologic surgery,
2024-Apr-01, 2024-04-00, 20240401, Letnik:
50, Številka:
4
Journal Article
Background
The objective of this systematic review and meta-analysis were to evaluate the effectiveness of high fluid intake for the prevention of incident and recurrent kidney stones, as well as its ...adherence and safety.
Methods
A literature search was performed encompassing 1980 through July 2014. Studies that reported relative risks, odds ratios, or hazard ratios comparing the risk of kidney stone events in patients with high vs inadequate fluid intake were included. Pooled risk ratios (RRs) and 95 % confidence intervals (CIs) were calculated using a random-effect, generic inverse variance method.
Results
Nine studies 2 randomized controlled trials (RCTs) with 269 patients; 7 observational studies with 273,685 individuals were included in the meta-analysis. Pooled RRs of kidney stones in individuals with high-fluid intake were 0.40 (95 % CI 0.20–0.79) and 0.49 (0.34–0.71) in RCTs and observational studies, respectively. High fluid intake was significantly associated with reduced risk of recurrent kidney stones: RRs 0.40 (95 % CI 0.20–0.79) and 0.20 (0.09–0.44) in RCTs and observational studies, respectively. Adherence and safety data on high fluid intake treatment were limited; 1 RCT reported no withdrawals due to adverse events.
Conclusion
This analysis demonstrated a significantly reduced risk of incident kidney stones among individuals with high fluid consumption. High fluid consumption also reduced the risk of recurrent kidney stones. Furthermore, the magnitude of risk reduction was high. Although increased water intake appears to be safe, future studies on its safety in patients with high risk of volume overload or hyponatremia may be indicated.
Vincristine combined with camptothecin derivatives showed synergy in preclinical pediatric cancer models, and the combinations are effective in treatment of childhood solid tumors. We determined ...whether the synergy between vincristine and irinotecan extends to eribulin, another microtubule inhibitor.
Vincristine or eribulin, alone or combined with irinotecan, was studied in 12 xenograft models. Tumor regression and time to event were used to assess antitumor activity. Pharmacodynamic studies and RNA sequencing (RNA-seq) were conducted 24 and 144 hours after single-agent or combination treatment. Effects on vascular development were studied in Matrigel plugs implanted in mice. The interaction between binary combinations was examined
.
Eribulin combined with irinotecan was more effective than vincristine-irinotecan in 6 of 12 models. Pharmacodynamic markers induced by eribulin (phospho-histone H3) and irinotecan (γ-H2A.X) were abrogated in combination-treated tumors. The predominant RNA-seq signature in combination-treated tumors was activation of the TP53 pathway with increased nuclear TP53. Massive apoptosis was observed 24 hours only after treatment with the eribulin combination.
, neither combination showed interaction using combination index analysis. Eribulin alone and the combination caused alterations in developing vasculature.
The eribulin combination is very active in these xenograft models, but not synergistic
. The combination reduced pharmacodynamic markers indicative of single-agent mechanisms but in tumors, dramatically activated the TP53 pathway. Although a mechanism for
synergy requires further study, it is possible that eribulin-induced inhibition of microtubule dynamics enhances irinotecan-induced nuclear accumulation of TP53, leading to rapid cell death.
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