Two modules of the AD detector have been studied with the test beam at the T10 facility at CERN. The AD detector is made of scintillator pads read out by wave-length shifters (WLS) coupled to clean ...fibres that carry the produced light to photo-multiplier tubes (PMTs). In ALICE the AD is used to trigger and study the physics of diffractive and ultra-peripheral collisions as well as for a variety of technical tasks like beam-gas background monitoring or as a luminometer. \par The position dependence of the modules' efficiency has been measured and the effect of hits on the WLS or PMTs has been evaluated. The charge deposited by pions and protons has been measured at different momenta of the test beam. The time resolution is determined as a function of the deposited charge. These results are important ingredients to better understand the AD detector, to benchmark the corresponding simulations, and very importantly they served as a baseline for a similar device, the Forward Diffractive Detector (FDD), being currently built and that will be in operation in ALICE during the LHC Runs 3 and 4.
Abstract
Background: Triple negative breast cancers (TNBC) have a greater risk of relapse than non-TNBC. New therapeutic approaches are needed for these patients (pts). CIBOMA/2004-01_GEICAM/2003-11 ...is a multinational, randomized phase III trial exploring adjuvant capecitabine (X) after completion of standard treatment in early TNBC pts.
Materials and Methods: Patients with operable, node-positive (or node-negative with tumor size ≥ 1 cm), centrally confirmed hormone receptor-negative, HER2-negative early BC, who had received 6–8 cycles (cy) of standard anthracycline and/or taxane-containing chemotherapy or 4 cy of doxorubicin-cyclophosphamide (for node-negative disease) in the (neo)adjuvant setting, were eligible. Patients were randomized to either 8 cy of X (1,000 mg/m2 bid, days 1–14, every 3 weeks) or observation. Stratification factors included center, prior taxane-based therapy, number of involved axillary lymph nodes and phenotype (basal vs non-basal, according to cytokeratins 5/6 and/or EGFR positivity). The primary objective was to compare the disease-free survival (DFS) between both treatment arms, and secondary objectives included the comparison in terms of 5-year DFS, overall survival (OS) and safety. Assuming a 30% risk reduction in DFS rate at 5 years (from 64.7% to 73.7%, hazard ratio 0.70) with 80% power and a two-tailed log-rank test at 0.05, 834 evaluable pts were needed. 876 pts had to be finally enrolled considering a drop-out rate of 5%.
Results: Recruitment of 876 pts from 8 countries was completed in September 2011. Median age was 49 years; 68.5% of pts were postmenopausal, 55.5% were lymph node negative, 71.7% had a basal phenotype, 67.5% received chemotherapy based on anthracyclines and taxanes. Median follow-up was 7.3 years (range 0.0 to 11.1). DFS was not significantly prolonged with X vs observation (hazard ratio (HR) 0.82; 95% confidence interval (CI), 0.63 to 1.06; P=0.1353). Five-year DFS was 79.6% (95% CI, 75.8% to 83.4%) with X and 76.8% (95% CI, 72.7% to 80.9%) with observation. OS was not statistically different between treatment arms (HR 0.92; 95% CI, 0.66 to 1.28; P=0.6228). In subgroup analysis for DFS, we found no statistically significant interaction between X treatment and different subgroups, with the exception of basal vs non-basal phenotypes (basal HR 0.97, 95% CI 0.72 to 1.32, P=0.8620; non-basal HR 0.51, 95% CI, 0.31 to 0.86, P=0.0101; interaction P=0.0357). Similar results were found for OS (basal HR 1.20, 95% CI 0.81 to 1.77, P=0.3684; non-basal HR 0.48, 95% CI, 0.26 to 0.91, P=0.0205; interaction P=0.0155). 75.2% of pts completed 8 cy of X, with a median relative dose intensity of 86.3%. Grade (G) 3 or higher adverse events (AEs) were observed in 40.4% of pts in X arm. In 9.6% of pts the AEs were related with X. Hand-foot syndrome was the most common AE in X arm (G3 on 18.8% of pts).
Conclusions: In our study, the addition of adjuvant X after standard (neo) adjuvant anthracycline and/or taxane-containing chemotherapy was not associated with a statistically significant improvement of DFS or OS compared to observation in pts with early TNBC. However, in a subgroup analysis a significant DFS and OS improvement was observed with X in pts with non-basal phenotype.
Sponsor: CIBOMA.
Citation Format: Martín M, Barrios CH, Torrecillas L, Ruiz-Borrego M, Bines J, Segalla J, Ruiz A, García-Sáenz JA, Torres R, de la Haba J, García E, Gómez HL, Llombart A, Rodríguez de la Borbolla M, Baena JM, Barnadas A, Calvo L, Pérez-Michel L, Ramos M, Castellanos J, Rodríguez-Lescure A, Cárdenas J, Vinholes J, Martínez de Dueñas E, Godes MJ, Seguí MA, Antón A, López-Álvarez P, Moncayo J, Amorim G, Villar E, Reyes S, Sampaio C, Cardemil B, Escudero MJ, Bezares S, Carrasco E, Lluch A. Efficacy results from CIBOMA/2004-01_GEICAM/2003-11 study: A randomized phase III trial assessing adjuvant capecitabine after standard chemotherapy for patients with early triple negative breast cancer abstract. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS2-04.
Two modules of the AD detector have been studied with the test beam at the T10 facility at CERN. The AD detector is made of scintillator pads read out by wave-length shifters (WLS)coupled to clean ...fibres that carry the produced light to photo-multiplier tubes (PMTs). In ALICE the AD is used to trigger and study the physics of diffractive and ultra-peripheral collisions as well as for a variety of technical tasks like beam-gas background monitoring or as a luminometer. The position dependence of the modules' efficiency has been measured and the effect of hits on the WLS or PMTs has been evaluated. The charge deposited by pions and protons has been measured at different momenta of the test beam. The time resolution is determined as a function of the deposited charge. These results are important ingredients to better understand the AD detector, to benchmark the corresponding simulations, and very importantly they served as a baseline for a similar device, the Forward Diffractive Detector (FDD), being currently built and that will be in operation in ALICE during the LHC Runs 3 and 4.
This paper presents a framework which, starting from a UML/MARTE model of the embedded system, relies on an enhanced IP-XACT description of the platform for the automatic generation of fast ...performance executable models. The IP-XACT description of the HW architecture is automatically generated from the UML/MARTE model. The enhancement proposed extends the current capabilities of the IP-XACT standard in order to add semantic information to the HW architecture and to support the integration of Hardware Dependent Software (HdS). This way, HW and SW aspects of the integration of a component in a virtual platform model are covered. The applicability of the proposed extensions is shown by supporting the proposed IP-XACT descriptions at the front-end of a simulation infrastructure suited for fast performance assessment, and for supporting design space exploration.
Local relapse and peritoneal carcinomatosis (PC) for pT4 colon cancer is estimated in 15,6% and 36,7% for 12 months and 36 months from surgical resection respectively, achieving a 5 years overall ...survival of 6%. There are promising results using prophylactic HIPEC in this group of patients, and it is estimated that up to 26% of all T4 colon cancer could benefit from this treatment with a minimal morbidity. Adjuvant HIPEC is effective to avoid the possibility of peritoneal seeding after surgical resection. Taking into account these results and the cumulative experience in HIPEC use, we will lead a randomized controlled trial to determine the effectiveness and safety of adjuvant treatment with HIPEC vs. standard treatment in patients with colon cancer at high risk of peritoneal recurrence (pT4).
The aim of this study is to determine the effectiveness and safety of adjuvant HIPEC in preventing the development of PC in patients with colon cancer with a high risk of peritoneal recurrence (cT4). This study will be carried out in 15 Spanish HIPEC centres. Eligible for inclusion are patients who underwent curative resection for cT4NxM0 stage colon cancer. After resection of the primary tumour, 200 patients will be randomized to adjuvant HIPEC followed by routine adjuvant systemic chemotherapy in the experimental arm, or to systemic chemotherapy only in the control arm. Adjuvant HIPEC will be performed simultaneously after the primary resection. Mitomycin C will be used as chemotherapeutic agent, for 60 min at 42-43 °C. Primary endpoint is loco-regional control (LC) in months and the rate of loco-regional control (%LC) at 12 months and 36 months after resection.
We assumed that adjuvant HIPEC will reduce the expected absolute risk of peritoneal recurrence from 36% to 18% at 36 months for T4 colon-rectal carcinoma.
NCT02614534 ( clinicaltrial.gov ) Nov-2015.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
CpG island hypermethylation and global genomic hypomethylation are common epigenetic features of cancer cells. Less attention has been focused on histone modifications in cancer cells. We ...characterized post-translational modifications to histone H4 in a comprehensive panel of normal tissues, cancer cell lines and primary tumors. Using immunodetection, high-performance capillary electrophoresis and mass spectrometry, we found that cancer cells had a loss of monoacetylated and trimethylated forms of histone H4. These changes appeared early and accumulated during the tumorigenic process, as we showed in a mouse model of multistage skin carcinogenesis. The losses occurred predominantly at the acetylated Lys16 and trimethylated Lys20 residues of histone H4 and were associated with the hypomethylation of DNA repetitive sequences, a well-known characteristic of cancer cells. Our data suggest that the global loss of monoacetylation and trimethylation of histone H4 is a common hallmark of human tumor cells.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Background
Mechanical hyperkeratotic lesions (MHL) are common condition amongst population of all ages. Such problems may be associated with pain, reduction in mobility, changes of gait and risk of ...falls and is believed to affect the quality of life (QoL), general health and optimal foot health.
Objective
The main aim of this study was to describe and compare both foot and general health‐related QoL in two groups of participants: (i) with MHL and (ii) healthy controls.
Method
A total sample of 150 patients, mean age 49.50 ± 36.50 years, was recruited from an outpatient clinic. Demographic data, medical history and clinical characteristics of overall health were determined, and the obtained values were compared by the Foot Health Status Questionnaire (FHSQ).
Results
The FHSQ scores of the sample with MHL showed lower scores than control subjects in sections one and two for footwear, general and foot health, foot pain, foot function and physical activity (P < 0.01), but not for social capacity and vigour (P > 0.01).
Conclusions
People with MHL showed a decrease in QoL, based on FHSQ scores, regardless of gender.
1. Peripheral blood serum alpha-L-fucosidases have been studied from various mammalian species: Sus scropha var domestica L. (pig), Capra hircus L. (goat), Bos taurus L. (bull, races Morucha and ...Charolais), Equus caballus L. (horse) and Equus asinus L. (donkey). 2. Fluorimetric and spectrophotometric procedures were used for determination of alpha-L-fucosidases. 3. alpha-L-Fucosidases were more active towards fluorescent substrates than towards chromogenic substrates. 4. pH optima values of the enzymes are: (A) 5.5 for sera from all above-mentioned species when fluorescent substrates were employed; (B) 4.0 for goat, 4.5 for bull, 5.0 for pig and 4.5-5.0 for horse and donkey sera when chromogenic substrates were used. 5. pH activity profiles are very similar for two races (Morucha and Charolais) of the same species (Bos taurus L.) and also for two species of the same genus (Equus caballus and Equus asinus L.). 6. These serum alpha-L-fucosidases are very labile under heat treatment, even at 37 degrees C.
Objectives
To describe and analyse erythromycin resistance trends in blood isolates of
Staphylococcus aureus
(EARS-Net Spain, 2004–2020) and the association of these trends with the consumption of ...macrolide, lincosamide, and streptogramin B (MLS
B
) antibiotics. To assess molecular changes that could be involved in erythromycin resistance trends by whole genome analysis of representative isolates.
Materials and methods
We collected antibiotic susceptibility data for all first-blood
S. aureus
isolates in patients from 47 Spanish hospitals according to EARS-Net criteria. MLS
B
antibiotic consumption was obtained from the Spanish Agency for Medicines and Medical Devices (2008–2020). We sequenced 137 representative isolates for core genome multilocus sequence typing, resistome and virulome analysis.
Results
For the 36,612 invasive
S. aureus
isolates, methicillin resistance decreased from 26.4% in 2004 to 22.4% in 2020. Erythromycin resistance in methicillin-susceptible
S. aureus
(MSSA) increased from 13.6% in 2004 to 28.9% in 2020 (
p
< 0.001); however, it decreased from 68.7 to 61.8% (
p
< 0.0001) in methicillin-resistant
S. aureus
(MRSA). Total consumption of MLS
B
antibiotics increased from 2.72 defined daily doses per 1,000 inhabitants per day (DID) in 2014 to 3.24 DID in 2016. By WGS, the macrolide resistance genes detected were
erm
(59.8%),
msrA
(46%), and
mphC
(45.2%). The
erm
genes were more prevalent in MSSA (44/57, 77.2%) than in MRSA (38/80, 47.5%). Most of the
erm
genes identified in MSSA after 2013 differed from the predominant
ermC
gene (17/22, 77.3%), largely because
ermT
was significantly associated with MSSA after 2013 (11/29, 37.9%). All 13
ermT
isolates in this study, except one, belonged to ST398 and came from 10 hospitals and six Spanish provinces.
Conclusion
The significant increase in erythromycin resistance in blood MSSA correlated with the consumption of the MLS
B
antibiotics in Spain. These preliminary data seem support the hypothesis that the human ST398 MSSA clade with
ermT
-mediated resistance to erythromycin may be involved in this trend.
Do not do in COPD: consensus statement on overuse Villar-Álvarez, Felipe; Moreno-Zabaleta, Raúl; Mira-Solves, Jose Joaquin ...
International journal of chronic obstructive pulmonary disease,
01/2018, Letnik:
13
Journal Article
Recenzirano
Odprti dostop
To identify practices that do not add value, cause harm, or subject patients with chronic obstructive pulmonary disease (COPD) to a level of risk that outweighs possible benefits (overuse).
A ...qualitative approach was applied. First, a multidisciplinary group of healthcare professionals used the Metaplan technique to draft and rank a list of overused procedures as well as self-care practices in patients with stable and exacerbated COPD. Second, in successive consensus-building rounds, description files were created for each "do not do" (DND) recommendation, consisting of a definition, description, quality of supporting evidence for the recommendation, and the indicator used to measure the degree of overuse. The consensus group comprised 6 pulmonologists, 2 general practitioners, 1 nurse, and 1 physiotherapist.
In total, 16 DND recommendations were made for patients with COPD: 6 for stable COPD, 6 for exacerbated COPD, and 4 concerning self-care.
Overuse poses a risk for patients and jeopardizes care quality. These 16 DND recommendations for COPD will lower care risks and improve disease management, facilitate communication between physicians and patients, and bolster patient ability to provide self-care.
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