While patient-derived xenografts (PDXs) offer a powerful modality for translational cancer research, a precise evaluation of how accurately patient responses correlate with matching PDXs in a large, ...heterogeneous population is needed for assessing the utility of this platform for preclinical drug-testing and personalized patient cancer treatment.
Tumors obtained from surgical or biopsy procedures from 237 cancer patients with a variety of solid tumors were implanted into immunodeficient mice and whole-exome sequencing was carried out. For 92 patients, responses to anticancer therapies were compared with that of their corresponding PDX models.
We compared whole-exome sequencing of 237 PDX models with equivalent information in The Cancer Genome Atlas database, demonstrating that tumorgrafts faithfully conserve genetic patterns of the primary tumors. We next screened PDXs established for 92 patients with various solid cancers against the same 129 treatments that were administered clinically and correlated patient outcomes with the responses in corresponding models. Our analysis demonstrates that PDXs accurately replicate patients’ clinical outcomes, even as patients undergo several additional cycles of therapy over time, indicating the capacity of these models to correctly guide an oncologist to treatments that are most likely to be of clinical benefit.
Integration of PDX models as a preclinical platform for assessment of drug efficacy may allow a higher success-rate in critical end points of clinical benefit.
Summary
A new procedure was developed and applied to study immunoglobulin free light chains (FLC) in saliva of healthy subjects and patients with multiple sclerosis (MS). The procedure was based on a ...Western blot analysis for detection and semiquantitative evaluation of monomeric and dimeric FLCs. The FLC indices accounting for the total FLC levels and for the monomer/dimer ratios of κ and λ FLC were calculated, and the cut‐off values of the FLC indices were determined to distinguish healthy state from MS disease. The obtained FLC index values were statistically different in the saliva of three groups: active MS patients, MS patients in remission and healthy subjects groups. Our FLC monomer–dimer analysis allowed differentiation between healthy state and active MS with specificity of 100% and a sensitivity of 88·5%. The developed technique may serve as a new non‐invasive complementary tool to evaluate the disease state by differentiating active MS from remission with sensitivity of 89% and specificity of 80%.
A new procedure based on a semiquantitative Western blot analysis was developed to study saliva immunoglobulin free light chain (FLC) monomers (25 kDa) and dimers (50kDa) of κ and λ type. Striking differences were revealed by comparing saliva FLC monomer‐dimer patterns of active MS patients (a2, b2, c2, d2, e2) versus patients in remission (c1, d1, e1) or healthy subjects (a1 and b1): active MS patients showed abnormally elevated level of FLC monomers and/or of both monomeric and dimeric FLC. The developed technique may serve as a new non‐invasive complimentary tool to evaluate the MS disease state by differentiating active MS from remission with sensitivity of 89% and specificity of 80%.
High brightness, high charge electron beams are critical for a number of advanced accelerator applications. The initial emittance of the electron beam, which is determined by the mean transverse ...energy (MTE) and laser spot size, is one of the most important parameters determining the beam quality. The bialkali photocathodes illuminated by a visible laser have the advantages of high quantum efficiency (QE) and low MTE. Furthermore, Superconducting Radio Frequency (SRF) guns can operate in the continuous wave (CW) mode at high accelerating gradients, e.g. with significant reduction of the laser spot size at the photocathode. Combining the bialkali photocathode with the SRF gun enables generation of high charge, high brightness, and possibly high average current electron beams. However, integrating the high QE semiconductor photocathode into the SRF guns has been challenging. In this article, we report on the development of bialkali photocathodes for successful operation in the SRF gun with months-long lifetime while delivering CW beams with nano-coulomb charge per bunch. This achievement opens a new era for high charge, high brightness CW electron beams.
Continuous-wave photoinjectors operating at high accelerating gradients promise to revolutionize many areas of science and applications. They can establish the basis for a new generation of ...monochromatic x-ray free electron lasers, high-brightness hadron beams, or a new generation of microchip production. In this Letter we report on the record-performing superconducting rf electron gun with CsK2 Sb photocathode. The gun is generating high charge electron bunches (up to 10 nC / bunch ) and low transverse emittances, while operating for months with a single photocathode. This achievement opens a new era in generating high-power beams with a very high average brightness.
Cooling of beams of gold ions using electron bunches accelerated with radio-frequency systems was recently experimentally demonstrated in the Relativistic Heavy Ion Collider at Brookhaven National ...Laboratory. Such an approach is new and opens the possibility of using this technique at higher energies than possible with electrostatic acceleration of electron beams. The challenges of this approach include generation of electron beams suitable for cooling, delivery of electron bunches of the required quality to the cooling sections without degradation of beam angular divergence and energy spread, achieving the required small angles between electron and ion trajectories in the cooling sections, precise velocity matching between the two beams, high-current operation of the electron accelerator, as well as several physics effects related to bunched-beam cooling. Here we report on the first demonstration of cooling hadron beams using this new approach.
High-Gain Harmonic-Generation Free-Electron Laser L.-H. Yu; Babzien, M.; Ben-Zvi, I. ...
Science (American Association for the Advancement of Science),
08/2000, Volume:
289, Issue:
5481
Journal Article
Peer reviewed
A high-gain harmonic-generation free-electron laser is demonstrated. Our approach uses a laser-seeded free-electron laser to produce amplified, longitudinally coherent, Fourier transform-limited ...output at a harmonic of the seed laser. A seed carbon dioxide laser at a wavelength of 10.6 micrometers produced saturated, amplified free-electron laser output at the second-harmonic wavelength, 5.3 micrometers. The experiment verifies the theoretical foundation for the technique and prepares the way for the application of this technique in the vacuum ultraviolet region of the spectrum, with the ultimate goal of extending the approach to provide an intense, highly coherent source of hard x-rays.
Objectives: Temporal artery biopsy (TAB) is performed in patients suspected of giant cell arteritis (GCA). Inadequate TAB specimen length is considered a possible explanation for a negative biopsy in ...patients with GCA. We investigated the association between specimen length and diagnostic yield of TAB.
Method: We conducted a retrospective analysis of 240 patients who underwent TAB in a single hospital between 2000 and 2015. Patients were diagnosed with GCA based on positive TAB or, when TAB was negative, on clinical grounds that fulfilled the American College of Rheumatology (ACR) 1990 criteria. Baseline clinical and laboratory features and TAB length were obtained from medical records. Among patients diagnosed with GCA, the rate of TAB positivity was calculated according to biopsy length (< 5, 5-9, 10-14, and ≥ 20 mm).
Results: Out of 240 patients, 88 were diagnosed with GCA: 62 had a positive TAB and 26 were diagnosed based on clinical grounds despite a negative TAB. Among those who were diagnosed with GCA, the length of the TAB specimen was similar in those with a positive and a negative TAB (1.13 ± 1.68 mm vs. 1.15 ± 0.61 mm, respectively, p = 0.928). The TAB positivity rate was similar among all ranges of biopsy length < 5 mm: 7/10 (70%); 5-9 mm: 22/31 (71%); 10-14 mm: 11/16 (69%); 15-19 mm: 11/16 (69%); ≥ 20 mm: 11/15 (73%, p = ns and was similar to the overall biopsy positivity rate.
Conclusions: Specimen length is not associated with diagnostic yield of TAB.
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