740 research outputs found
EP05.02-003 Durvalumab after Chemoradiotherapy (CRT) in Unresectable Stage III NSCLC. Comparative Study of Two Cohorts in the Real-World Setting
[EN] Introduction: Durvalumab is the new standard of care for unresectable
locally advanced NSCLC, with PD-L1 _1% and who did not
have progression after CRT treatment in the European Union. Our
study compares the effectiveness and the frequency of radiation
pneumonitis in patients treated with concurrent CRT with or without
durvalumab consolidation during the same period in real clinical
practice. Methods: A single-center retrospective study. 71 treated
patients with unresectable stage III NSCLC were included between
March 2018 and December 2021, 37 with CRT followed by durvalumab
and 34 with CRT alone. Real-world progression-free survival
(rwPFS) and real-world overall survival (rwOS) were calculated since
the date of the end CRT. Propensity score matching (PSM) 1:1 was
used to account for differences in baseline characteristics. Results:
Median age was 67 years (range 46-82). 25.4% of the patients were
_75 years old. 78.9% were men and 53.5% former smokers. 54.9%
had squamous histology and 28%, 51% and 21% stage IIIA, IIIB and
IIIC disease, respectively. The most used scheme was carboplatinpaclitaxel
(43.7%), receiving induction chemotherapy in up to 54.9%
of patients. 73.2% received between 60-66 Gy doses of radiotherapy.
Median time from end of CRT to onset durvalumab was 44 days
(range 13-120) with a median of 14 infusions (range 6-27). Of the
34 patients without durvalumab treatment, the expression PD-L1
<1% (58.8%) was the most frequent cause for rejecting consolidation
therapy. After PSM analysis, patients distributions were well
balanced. With a median follow-up of 19.7 months (range 1.4-36.6);
median rw-PFS was 9.3 months (95% CI, 5-13.5) without durvalumab
and 17 months (95% CI, 11-22.9) with durvalumab (p¼0.013).
Median rw-OS was 19.3 months (95% CI, 3.8-34.8) without durvalumab
and 29.9 months (95% CI, 23.3-36.6) with durvalumab
(p¼0.241) with a rw-OS% at 6, 18 and 24 months of 90%, 62% and
49% vs 100%, 86% and 74%, respectively. The rate of radiation
pneumonitis was more frequent with durvalumab consolidation
(56.8% against 44.1%), (p¼0.346), especially within 3 months after
CRT. G3 pneumonitis was only observed in the consolidation therapy.
Conclusions: Our results demonstrate the effectiveness of
durvalumab consolidation after CRT in real-world patients with
unresectable stage III NSCLC. Further sample and longer follow-up
are required to obtain more accurate results. Active surveillance and
appropriate management for radiation pneumonitis are needed, in
especially in candidates for consolidation treatmentS
EP05.02-002 Who Benefits More of Durvalumab after Chemoradiotherapy (CRT) in Real-World Patients with Locally Advanced Non-Small-Cell Lung Cancer (NSCLC)?
[EN] Introduction: Durvalumab received EMA approval as consolidation
therapy (CT) for unresectable stage III NSCLC with PD-L1 _1% and
who did not have progression after CRT. Our objective was to analyze
in real clinical practice the effectiveness of durvalumab and explore the
clinical factors that may be associated with the benefit from CT.
Methods: Retrospective study was made at Hospital of Leon (Spain),
including 37 patients with locally advanced NSCLC treated with durvalumab
after CRT treatment between March 2018 and october 2021
(40.5% patients were included in the durvalumab early access program).
The neutrophil-to-lymphocyte ratio (NLR) could identified after
CRT as a factor that may be benefit from durvalumab. Results: Median
age was 67 years (range 46-82 years). 40.5% of patients were _70
years old. 78.4% were male and 51.4% smokers. 54% had non-squamous
histology. PD-L1 expression was <1% in 5% and not available in
8% patients. 2.7% ROS1 rearrangements, 5.4% KRAS mutations and
not available in 43.2% patients. Stage IIIA, IIIB, IIIC disease were
24.3%, 54.1% and 21.6%, respectively. Median time from end of CRT to
onset durvalumab was 44 days (range 13-120 days). Overall median CT
duration was 214.8 days (range 69-399 days) with a median of 14
infusions (range 6-27 infusions). With a median follow up of 19.7
months (range 1.4-34.9 months); 67.6% had stopped CT: 37.8% due to
completing treatment, 16.2% disease progression, 10.8% adverse event
and 2.7% due to COVID19 infection. Median real-world progressionfree
survival (rwPFS) was 17 months (95% CI, 11-23). Median realworld
overall survival (rwOS) was 29.9 months (95% CI, 23.3-36.6). %
rwOS at 6, 18 and 24 months were 100%, 86.9% and 74.5%, respectively.
For patients with post-CRT NLR not exceeding the cohort median
value of 6, receipt of durvalumab was associated with an improvement
in rwOS (median not reached vs 25.7 months; p¼0.025). 56.8% patients
had any grade of radiation pneumonitis (median time from CRT
start: 119 days [range 36-241 days]). Of these, 19% patients developed
worsening of radiation pneumonitis with durvalumab. 54,1% developed
immune-mediated toxicity, mostly G1-2 (85.1%). Conclusions:
Our results demonstrate the effectiveness of durvalumab consolidation
in this patients population in a real-life setting. We identified low NLR
after CRT as a potentially predictive factor for the benefit of CT in
locally advanced NSCLC.S
A new view of electrochemistry at highly oriented pyrolytic graphite
Major new insights on electrochemical processes at graphite electrodes are reported, following extensive investigations of two of the most studied redox couples, Fe(CN)64–/3– and Ru(NH3)63+/2+. Experiments have been carried out on five different grades of highly oriented pyrolytic graphite (HOPG) that vary in step-edge height and surface coverage. Significantly, the same electrochemical characteristic is observed on all surfaces, independent of surface quality: initial cyclic voltammetry (CV) is close to reversible on freshly cleaved surfaces (>400 measurements for Fe(CN)64–/3– and >100 for Ru(NH3)63+/2+), in marked contrast to previous studies that have found very slow electron transfer (ET) kinetics, with an interpretation that ET only occurs at step edges. Significantly, high spatial resolution electrochemical imaging with scanning electrochemical cell microscopy, on the highest quality mechanically cleaved HOPG, demonstrates definitively that the pristine basal surface supports fast ET, and that ET is not confined to step edges. However, the history of the HOPG surface strongly influences the electrochemical behavior. Thus, Fe(CN)64–/3– shows markedly diminished ET kinetics with either extended exposure of the HOPG surface to the ambient environment or repeated CV measurements. In situ atomic force microscopy (AFM) reveals that the deterioration in apparent ET kinetics is coupled with the deposition of material on the HOPG electrode, while conducting-AFM highlights that, after cleaving, the local surface conductivity of HOPG deteriorates significantly with time. These observations and new insights are not only important for graphite, but have significant implications for electrochemistry at related carbon materials such as graphene and carbon nanotubes
Origin and function of short-latency inputs to the neural substrates underlying the acoustic startle reflex
The acoustic startle reflex (ASR) is a survival mechanism of alarm, which rapidly alerts the organism to a sudden loud auditory stimulus. In rats, the primary ASR circuit encompasses three serially connected structures: cochlear root neurons (CRNs), neurons in the caudal pontine reticular nucleus (PnC), and motoneurons in the medulla and spinal cord. It is well-established that both CRNs and PnC neurons receive short-latency auditory inputs to mediate the ASR. Here, we investigated the anatomical origin and functional role of these inputs using a multidisciplinary approach that combines morphological, electrophysiological and behavioral techniques. Anterograde tracer injections into the cochlea suggest that CRNs somata and dendrites receive inputs depending, respectively, on their basal or apical cochlear origin. Confocal colocalization experiments demonstrated that these cochlear inputs are immunopositive for the vesicular glutamate transporter 1 (VGLUT1). Using extracellular recordings in vivo followed by subsequent tracer injections, we investigated the response of PnC neurons after contra-, ipsi-, and bilateral acoustic stimulation and identified the source of their auditory afferents. Our results showed that the binaural firing rate of PnC neurons was higher than the monaural, exhibiting higher spike discharges with contralateral than ipsilateral acoustic stimulations. Our histological analysis confirmed the CRNs as the principal source of short-latency acoustic inputs, and indicated that other areas of the cochlear nucleus complex are not likely to innervate PnC. Behaviorally, we observed a strong reduction of ASR amplitude in monaural earplugged rats that corresponds with the binaural summation process shown in our electrophysiological findings. Our study contributes to understand better the role of neuronal mechanisms in auditory alerting behaviors and provides strong evidence that the CRNs-PnC pathway mediates fast neurotransmission and binaural summation of the ASR
Constraints on the steady and pulsed very high energy gamma-ray emission from observations of PSR B1951+32/CTB 80 with the MAGIC Telescope
We report on very high energy gamma-observations with the MAGIC Telescope of
the pulsar PSR B1951+32 and its associated nebula, CTB 80. Our data constrain
the cutoff energy of the pulsar to be less than 32 GeV, assuming the pulsed
gamma-ray emission to be exponentially cut off. The upper limit on the flux of
pulsed gamma-ray emission above 75 GeV is 4.3*10^-11 photons cm^-2 sec^-1, and
the upper limit on the flux of steady emission above 140 GeV is 1.5*10^-11
photons cm^-2 sec^-1. We discuss our results in the framework of recent model
predictions and other studies.Comment: 7 pages, 7 figures, replaced with published versio
Estimation of the real population and its impact on the utilisation of healthcare services in Mediterranean resort regions: an ecological study
BACKGROUND: The demographic structure has a significant influence on the use of healthcare services, as does the size of the population denominators. Very few studies have been published on methods for estimating the real population such as tourist resorts. The lack of information about these problems means there is a corresponding lack of information about the behaviour of populational denominators (the floating population or tourist load) and the effect of this on the use of healthcare services. The objectives of the study were: a) To determine the Municipal Solid Waste (MSW) ratio, per person per day, among populations of known size; b) to estimate, by means of this ratio, the real population in an area where tourist numbers are very significant; and c) to determine the impact on the utilisation of hospital emergency healthcare services of the registered population, in comparison to the non-resident population, in two areas where tourist numbers are very significant. METHODS: An ecological study design was employed. We analysed the Healthcare Districts of the Costa del Sol and the island of Menorca. Both are Spanish territories in the Mediterranean region. RESULTS: In the two areas analysed, the correlation coefficient between the MSW ratio and admissions to hospital emergency departments exceeded 0.9, with p < 0.001. On the basis of MSW generation ratios, obtained for a control zone and also measured in neighbouring countries, we estimated the real population. For the summer months, when tourist activity is greatest and demand for emergency healthcare at hospitals is highest, this value was found to be double that of the registered population. CONCLUSION: The MSW indicator, which is both ecological and indirect, can be used to estimate the real population in areas where population levels vary significantly during the year. This parameter is of interest in planning and dimensioning the provision of healthcare services
Discovery of VHE Gamma Radiation from IC443 with the MAGIC Telescope
We report the detection of a new source of very high energy (VHE, E_gamma >=
100GeV) gamma-ray emission located close to the Galactic Plane, MAGIC
J0616+225, which is spatially coincident with SNR IC443. The observations were
carried out with the MAGIC telescope in the periods December 2005 - January
2006 and December 2006 - January 2007. Here we present results from this
source, leading to a VHE gamma-ray signal with a statistical significance of
5.7 sigma in the 2006/7 data and a measured differential gamma-ray flux
consistent with a power law, described as dN_gamma/(dA dt dE) = (1.0 +/-
0.2)*10^(-11)(E/0.4 TeV)^(-3.1 +/- 0.3) cm^(-2)s^(-1)TeV^(-1). We briefly
discuss the observational technique used and the procedure implemented for the
data analysis. The results are put in the perspective of the multiwavelength
emission and the molecular environment found in the region of IC443.Comment: Accepted by ApJ Letter
Observation of Pulsed Gamma-rays Above 25 GeV from the Crab Pulsar with MAGIC
One fundamental question about pulsars concerns the mechanism of their pulsed
electromagnetic emission. Measuring the high-end region of a pulsar's spectrum
would shed light on this question. By developing a new electronic trigger, we
lowered the threshold of the Major Atmospheric gamma-ray Imaging Cherenkov
(MAGIC) telescope to 25 GeV. In this configuration, we detected pulsed
gamma-rays from the Crab pulsar that were greater than 25 GeV, revealing a
relatively high cutoff energy in the phase-averaged spectrum. This indicates
that the emission occurs far out in the magnetosphere, hence excluding the
polar-cap scenario as a possible explanation of our measurement. The high
cutoff energy also challenges the slot-gap scenario.Comment: Slight modification of the analysis: Fitting a more general function
to the combined data set of COMPTEL, EGRET and MAGIC. Final result and
conclusion is unchange
The Zoning of Semi-Enclosed Bodies of Water According to the Sediment Pollution: The Bay of Algeciras as a Case Example
This paper reports a study of the occurrence and
levels of polycyclic aromatic hydrocarbons (PAHs) in a bay
characterised by a chronic persistent impact. A total of 55
sediment samples were taken at different depths up to
111 m in two sampling campaigns. Chemical analyses were
carried out by gas chromatography-mass spectroscopy. The
results indicate that: (1) significant spatial variations exist,
(2) levels of PAHs are related more strongly to the spatial
distribution of sediments than to mineralogy/granulometry,
(3) the sediments are slightly-to-moderately contaminated
by PAHs, and (4) these PAHs derive from pyrolytic and
petrogenic sources. Through use of an innovative data
classification system (proposed according to depth and
spatial location of sampling points), and using factorial and
cluster techniques, five zones have been differentiated
depending on the contamination level and source
Search for coherent charged pion production in neutrino-carbon interactions
We report the result from a search for charged-current coherent pion
production induced by muon neutrinos with a mean energy of 1.3 GeV. The data
are collected with a fully active scintillator detector in the K2K
long-baseline neutrino oscillation experiment. No evidence for coherent pion
production is observed and an upper limit of is set on
the cross section ratio of coherent pion production to the total
charged-current interaction at 90% confidence level. This is the first
experimental limit for coherent charged pion production in the energy region of
a few GeV.Comment: 5 pages, 4 figure
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