Cell-free DNA mutations as biomarkers in breast cancer patients receiving tamoxifen

The aim was to identify mutations in serum cell-free DNA (cfDNA) associated with disease progression on tamoxifen treatment in metastatic breast cancer (MBC). Sera available at start of therapy, during therapy and at disease progression were selected from 10 estrogen receptor (ER)-positive breast cancer patients. DNA from primary tumor and normal tissue and cfDNA from minute amounts of sera were analyzed by targeted next generation sequencing (NGS) of 45 genes (1,242 exons). At disease progression, stop-gain single nucleotide variants (SNVs) for CREBBP (1 patient) and SMAD4 (1 patient) and non-synonymous SNVs for AKAP9 (1 patient), PIK3CA (2 patients) and TP53 (2 patients) were found. Mutations in CREBBP and SMAD4 have only been occasionally reported in breast cancer. All mutations, except for AKAP9, were also present in the primary tumor but not detected in all blood specimens preceding progression. More sensitive detection by deeper re-sequencing and digital PCR confirmed the occurrence of circulating tumor DNA (ctDNA) and these biomarkers in blood specimens

Selection of the silicon sensor thickness for the Phase-2 upgrade of the CMS Outer Tracker

During the operation of the CMS experiment at the High-Luminosity LHC the silicon sensors of the Phase-2 Outer Tracker will be exposed to radiation levels that could potentially deteriorate their performance. Previous studies had determined that planar float zone silicon with n-doped strips on a p-doped substrate was preferred over p-doped strips on an n-doped substrate. The last step in evaluating the optimal design for the mass production of about 200 m$^{2}$ of silicon sensors was to compare sensors of baseline thickness (about 300 μm) to thinned sensors (about 240 μm), which promised several benefits at high radiation levels because of the higher electric fields at the same bias voltage. This study provides a direct comparison of these two thicknesses in terms of sensor characteristics as well as charge collection and hit efficiency for fluences up to 1.5 × 10$^{15}$ n$_{eq}$/cm$^{2}$. The measurement results demonstrate that sensors with about 300 μm thickness will ensure excellent tracking performance even at the highest considered fluence levels expected for the Phase-2 Outer Tracker

Comparative evaluation of analogue front-end designs for the CMS Inner Tracker at the High Luminosity LHC

The CMS Inner Tracker, made of silicon pixel modules, will be entirely replaced prior to the start of the High Luminosity LHC period. One of the crucial components of the new Inner Tracker system is the readout chip, being developed by the RD53 Collaboration, and in particular its analogue front-end, which receives the signal from the sensor and digitizes it. Three different analogue front-ends (Synchronous, Linear, and Differential) were designed and implemented in the RD53A demonstrator chip. A dedicated evaluation program was carried out to select the most suitable design to build a radiation tolerant pixel detector able to sustain high particle rates with high efficiency and a small fraction of spurious pixel hits. The test results showed that all three analogue front-ends presented strong points, but also limitations. The Differential front-end demonstrated very low noise, but the threshold tuning became problematic after irradiation. Moreover, a saturation in the preamplifier feedback loop affected the return of the signal to baseline and thus increased the dead time. The Synchronous front-end showed very good timing performance, but also higher noise. For the Linear front-end all of the parameters were within specification, although this design had the largest time walk. This limitation was addressed and mitigated in an improved design. The analysis of the advantages and disadvantages of the three front-ends in the context of the CMS Inner Tracker operation requirements led to the selection of the improved design Linear front-end for integration in the final CMS readout chip

Beam test performance of a prototype module with Short Strip ASICs for the CMS HL-LHC tracker upgrade

The Short Strip ASIC (SSA) is one of the four front-end chips designed for the upgrade of the CMS Outer Tracker for the High Luminosity LHC. Together with the Macro-Pixel ASIC (MPA) it will instrument modules containing a strip and a macro-pixel sensor stacked on top of each other. The SSA provides both full readout of the strip hit information when triggered, and, together with the MPA, correlated clusters called stubs from the two sensors for use by the CMS Level-1 (L1) trigger system. Results from the first prototype module consisting of a sensor and two SSA chips are presented. The prototype module has been characterized at the Fermilab Test Beam Facility using a 120 GeV proton beam

Test beam performance of a CBC3-based mini-module for the Phase-2 CMS Outer Tracker before and after neutron irradiation

The Large Hadron Collider (LHC) at CERN will undergo major upgrades to increase the instantaneous luminosity up to 5–7.5×10$^{34}$ cm$^{-2}$s$^{-1}$. This High Luminosity upgrade of the LHC (HL-LHC) will deliver a total of 3000–4000 fb-1 of proton-proton collisions at a center-of-mass energy of 13–14 TeV. To cope with these challenging environmental conditions, the strip tracker of the CMS experiment will be upgraded using modules with two closely-spaced silicon sensors to provide information to include tracking in the Level-1 trigger selection. This paper describes the performance, in a test beam experiment, of the first prototype module based on the final version of the CMS Binary Chip front-end ASIC before and after the module was irradiated with neutrons. Results demonstrate that the prototype module satisfies the requirements, providing efficient tracking information, after being irradiated with a total fluence comparable to the one expected through the lifetime of the experiment

The CMS Phase-1 pixel detector upgrade

The CMS detector at the CERN LHC features a silicon pixel detector as its innermost subdetector. The original CMS pixel detector has been replaced with an upgraded pixel system (CMS Phase-1 pixel detector) in the extended year-end technical stop of the LHC in 2016/2017. The upgraded CMS pixel detector is designed to cope with the higher instantaneous luminosities that have been achieved by the LHC after the upgrades to the accelerator during the first long shutdown in 2013–2014. Compared to the original pixel detector, the upgraded detector has a better tracking performance and lower mass with four barrel layers and three endcap disks on each side to provide hit coverage up to an absolute value of pseudorapidity of 2.5. This paper describes the design and construction of the CMS Phase-1 pixel detector as well as its performance from commissioning to early operation in collision data-taking.Peer reviewe

Consumo de alcohol entre estudiantes Mexicanos de medicina O uso de álcool entre estudantes de medicina Mexicanos Alcohol use among Mexican medical students

Este estudio tiene por objetivo identificar el patrón de consumo de alcohol entre los estudiantes mexicanos de medicina. Se trata de un estudio transversal realizado en la Universidad Veracruzana, en México, con 263 estudiantes (84,4%). El cuestionario contiene la Prueba de Identificación de Trastornos por el Uso del Alcohol y el Cuestionario de Estudiantes 2006. Los sujetos eran 60% mujeres, jóvenes. El uso en la vida fue de 71,9% y la edad de inicio 12,5 años. La frecuencia del consumo fue baja pero en alta cantidad, consumen en niveles de emborrachamiento, principalmente los hombres. El 46% consume bebidas en niveles problemáticos. Los estudiantes tienen la percepción de que los padres y maestros ven muy mal que ellos consuman bebidas alcohólicas. Este estudio tiene contribuciones para el planteamiento de programas preventivos en relación al consumo de bebidas alcohólicas para ser aplicados en el ámbito universitario.<br>O estudo teve por objetivo identificar o padrão de consumo de álcool entre estudantes de medicina mexicanos. Trata-se de estudo transversal, realizado na Universidade Veracruzana, México, com 263 estudantes (84.4%). Foram usados o questionário do teste de identificação do uso de álcool e o questionário de estudantes 2006. Os sujeitos eram mulheres jovens. O uso na vida foi de 71,9% e a idade de início 12,5 anos. A frequência de consumo foi baixa, mas em alta quantidade, com padrão de embriaguez, principalmente entre os homens. Dos estudantes, 46% consomem bebidas alcoólicas em níveis problemáticos. Os estudantes percebem que os pais e professores avaliam muito mal o fato de eles consomirem bebidas alcoólicas. Este estudo traz contribuições para o planejamento de programas preventivos em relação ao consumo de bebidas alcoólicas, no âmbito universitário.<br>The study aims to identify patterns of alcohol consumption in Mexican medical students. This is a cross-sectional study, conducted at the University of Veracruz, Mexico. The sample comprised 263 students (84.4%). The Alcohol Use Disorders Identification Test and the Student Questionnaire 2006 were used. Students were characterized by youth and women. Seventy-two percent used alcohol in the lifetime, with 12.5 years as the onset age. The frequency of consumption was low but the quantity high, with a pattern of drunkenness, mainly among men. Forty-six percent consumed beverage at a problematic level. Students perceive that parents and teachers badly assess alcoholic beverage consumption. This study contributes to the planning of preventive programs for alcohol consumption, to be applied in the university context