ESÓFAGO DE BARRETT: REVISIÓN DE LA LITERATURA

RESUMENEl Esófago de Barrett (EB) es una patología adquirida producto del reflujo gastroesofágico crónico que provoca la lesión de la mucosa esofágica normal y su reemplazo por mucosa metaplásica. La importancia clínica del EB radica en que constituye un factor de riesgo para el desarrollo de adenocarcinoma esofágico. La incidencia del adenocarcinoma esofágico se encuentra en aumento y su diagnóstico se realiza generalmente en etapas avanzadas, teniendo un pronóstico sombrío. Actualmente el objetivo es detectar el cáncer en etapas iniciales y eventualmente tratables, para lo cual se han planteado distintos protocolos de vigilancia y numerosas alternativas de tratamiento del epitelio metaplásico del esófago de Barrett. En el siguiente artículo se revisan los conceptos más recientes de manejo.SUMMARYBarrett's esophagus is an acquired disease caused by chronic gastroesophageal reflux causing the injury of normal esophageal mucosa and its replacement by metaplastic mucosa. The clinical significance of Barrett's esophagus is that it constitutes a risk factor for the development of esophageal adenocarcinoma. The incidence of esophageal adenocarcinoma is increasing and its diagnosis is usually done in advanced stages, with grim prognosis. Currently the goal is to detect cancer in early, treatable stages. Different protocols have been proposed, numerous alternatives for monitoring and treating metaplastic epithelium of Barrett's esophagus. In the following article the latest management concepts are reviewed

Control and systems software for the Cosmology Large Angular Scale Surveyor (CLASS)

The Cosmology Large Angular Scale Surveyor (CLASS) is an array of polarization-sensitive millimeter wave telescopes that observes ~70% of the sky at frequency bands centered near 40GHz, 90GHz, 150GHz, and 220GHz from the Atacama desert of northern Chile. Here, we describe the architecture of the software used to control the telescopes, acquire data from the various instruments, schedule observations, monitor the status of the instruments and observations, create archival data packages, and transfer data packages to North America for analysis. The computer and network architecture of the CLASS observing site is also briefly discussed. This software and architecture has been in use since 2016, operating the telescopes day and night throughout the year, and has proven successful in fulfilling its design goals.Comment: 19 pages, 8 figures, to appear in Proc. SPI

EuroFlow Lymphoid Screening Tube (LST) data base for automated identification of blood lymphocyte subsets

In recent years the volume and complexity of flow cytometry data has increased substantially. This has led to a greater number of identifiable cell populations in a single measurement. Consequently, new gating strategies and new approaches for cell population definition are required. Here we describe how the EuroFlow Lymphoid Screening Tube (LST) reference data base for peripheral blood (PB) samples was designed, constructed and validated for automated gating of the distinct lymphoid (and myeloid) subsets in PB of patients with chronic lymphoproliferative disorders (CLPD). A total of 46 healthy/reactive PB samples which fulfilled predefined technical requirements, were used to construct the LST-PB reference data base. In addition, another set of 92 PB samples (corresponding to 10 healthy subjects, 51 B-cell CLPD and 31 T/NK-cell CLPD patients), were used to validate the automated gating and cell-population labeling tools with the Infinicyt software. An overall high performance of the LST-PB data base was observed with a median percentage of alarmed cellular events of 0.8% in 10 healthy donor samples and of 44.4% in CLPD data files containing 49.8% (range: 1.3–96%) tumor cells. The higher percent of alarmed cellular events in every CLPD sample was due to aberrant phenotypes (75.6% cases) and/or to abnormally increased cell counts (86.6% samples). All 18 (22%) data files that only displayed numerical alterations, corresponded to T/NK-cell CLPD cases which showed a lower incidence of aberrant phenotypes (41%) vs B-cell CLPD cases (100%). Comparison between automated vs expert-bases manual classification of normal (r2 = 0.96) and tumor cell populations (rho = 0.99) showed a high degree of correlation. In summary, our results show that automated gating of cell populations based on the EuroFlow LST-PB data base provides an innovative, reliable and reproducible tool for fast and simplified identification of normal vs pathological B and T/NK lymphocytes in PB of CLPD patients

CLASS Angular Power Spectra and Map-Component Analysis for 40 GHz Observations through 2022

Measurement of the largest angular scale ($\ell < 30$) features of the cosmic microwave background (CMB) polarization is a powerful way to constrain the optical depth to reionization, $\tau$, and search for the signature of inflation through the detection of primordial $B$-modes. We present an analysis of maps covering nearly 75% of the sky made from the ground-based $40\,\mathrm{GHz}$ channel of the Cosmology Large Angular Scale Surveyor (CLASS) from August 2016 to May 2022. Using fast front-end polarization modulation from the Atacama Desert in Chile, we show this channel achieves higher sensitivity than the analogous frequencies from satellite measurements in the range $10 < \ell < 100$. After a final calibration adjustment, noise simulations show the CLASS linear (circular) polarization maps have a white noise level of $125 \,(130)\,\mathrm{\mu K\, arcmin}$. We measure the Galaxy-masked $EE$ and $BB$ spectra of diffuse synchrotron radiation and compare to space-based measurements at similar frequencies. In combination with external data, we expand measurements of the spatial variations of the synchrotron spectral energy density (SED) to include new regions of the sky and measure the faint diffuse SED in the harmonic domain. We place a new upper limit on a background of circular polarization in the range $5 < \ell < 125$ with the first bin showing $D_\ell < 0.023$ $\mathrm{\mu K^2_{CMB}}$ at 95% confidence. These results establish a new standard for recovery of the largest-scale CMB polarization from the ground and signal exciting possibilities when the higher sensitivity and higher frequency CLASS channels are included in the analysis.Comment: 36 pages, 24 figures, 6 tables. Submitted to The Astrophysical Journa

Next Generation Flow for highly sensitive and standardized detection of minimal residual disease in multiple myeloma

[EN]Flow cytometry has become a highly valuable method to monitor minimal residual disease (MRD) and evaluate the depth of complete response (CR) in bone marrow (BM) of multiple myeloma (MM) after therapy. However, current flow-MRD has lower sensitivity than molecular methods and lacks standardization. Here we report on a novel next generation flow (NGF) approach for highly sensitive and standardized MRD detection in MM. An optimized 2-tube 8-color antibody panel was constructed in five cycles of design-evaluation-redesign. In addition, a bulk-lysis procedure was established for acquisition of ⩾107 cells/sample, and novel software tools were constructed for automatic plasma cell gating. Multicenter evaluation of 110 follow-up BM from MM patients in very good partial response (VGPR) or CR showed a higher sensitivity for NGF-MRD vs conventional 8-color flow-MRD -MRD-positive rate of 47 vs 34% (P=0.003)-. Thus, 25% of patients classified as MRD-negative by conventional 8-color flow were MRD-positive by NGF, translating into a significantly longer progression-free survival for MRD-negative vs MRD-positive CR patients by NGF (75% progression-free survival not reached vs 7 months; P=0.02). This study establishes EuroFlow-based NGF as a highly sensitive, fully standardized approach for MRD detection in MM which overcomes the major limitations of conventional flow-MRD methods and is ready for implementation in routine diagnostics.This work has been supported by the International Myeloma Foundation-Black Swan Research Initiative, the Red Temática de Investigación Cooperativa en Cáncer (RTICC); grant SA079U14 from the Consejería de Educación, Junta de Castilla y León, Valladolid, Spain and; grant DTS15/00119 from Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain

Two Year Cosmology Large Angular Scale Surveyor (CLASS) Observations: Long Timescale Stability Achieved with a Front-End Variable-delay Polarization Modulator at 40 GHz

The Cosmology Large Angular Scale Surveyor (CLASS) is a four-telescope array observing the largest angular scales ($2 \lesssim \ell \lesssim 200$) of the cosmic microwave background (CMB) polarization. These scales encode information about reionization and inflation during the early universe. The instrument stability necessary to observe these angular scales from the ground is achieved through the use of a variable-delay polarization modulator (VPM) as the first optical element in each of the CLASS telescopes. Here we develop a demodulation scheme used to extract the polarization timestreams from the CLASS data and apply this method to selected data from the first two years of observations by the 40 GHz CLASS telescope. These timestreams are used to measure the $1/f$ noise and temperature-to-polarization ($T\rightarrow P$) leakage present in the CLASS data. We find a median knee frequency for the pair-differenced demodulated linear polarization of 15.12 mHz and a $T\rightarrow P$ leakage of $<3.8\times10^{-4}$ (95\% confidence) across the focal plane. We examine the sources of $1/f$ noise present in the data and find the component of $1/f$ due to atmospheric precipitable water vapor (PWV) has an amplitude of $203 \pm 12 \mathrm{\mu K_{RJ}\sqrt{s}}$ for 1 mm of PWV when evaluated at 10 mHz; accounting for $\sim32\%$ of the $1/f$ noise in the central pixels of the focal plane. The low level of $T\rightarrow P$ leakage and $1/f$ noise achieved through the use of a front-end polarization modulator enables the observation of the largest scales of the CMB polarization from the ground by the CLASS telescopes.Comment: Submitted to Ap

Expert-independent classification of mature B-cell neoplasms using standardized flow cytometry: a multicentric study

Reproducible expert-independent flow-cytometric criteria for the differential diagnoses between mature B-cell neoplasms are lacking. We developed an algorithm-driven classification for these lymphomas by flow cytometry and compared it to the WHO gold standard diagnosis. Overall, 662 samples from 662 patients representing 9 disease categories were analyzed at 9 laboratories using the previously published EuroFlow 5-tube-8-color B-cell chronic lymphoproliferative disease antibody panel. Expression levels of all 26 markers from the panel were plotted by B-cell entity to construct a univariate, fully standardized diagnostic reference library. For multivariate data analysis, we subsequently used canonical correlation analysis of 176 training cases to project the multidimensional space of all 26 immunophenotypic parameters into 36 2-dimensional plots for each possible pairwise differential diagnosis. Diagnostic boundaries were fitted according to the distribution of the immunophenotypes of a given differential diagnosis. A diagnostic algorithm based on these projections was developed and subsequently validated using 486 independent cases. Negative predictive values exceeding 92.1% were observed for all disease categories except for follicular lymphoma. Particularly high positive predictive values were returned in chronic lymphocytic leukemia (99.1%), hairy cell leukemia (97.2%), follicular lymphoma (97.2%), and mantle cell lymphoma (95.4%). Burkitt and CD101 diffuse large B-cell lymphomas were difficult to distinguish by the algorithm. A similar ambiguity was observed between marginal zone, lymphoplasmacytic, and CD102 diffuse large B-cell lymphomas. The specificity of the approach exceeded 98% for all entities. The univariate immunophenotypic library and the multivariate expert-independent diagnostic algorithm might contribute to increased reproducibility of future diagnostics in mature B-cell neoplasms