6,321 research outputs found
Gnathostomosis, an emerging foodborne zoonotic disease in Acapulco, Mexico.
Between 1993 and 1997, 98 gnathostomosis cases were clinically identified in Acapulco, Mexico. Intermittent cutaneous migratory swellings were the commonest manifestation. Larvae were identified in 26 cases, while in 72, final diagnosis was made on the basis of epidemiologic data, food habits, and positive enzyme-linked immunosorbent assay and Western blot results
Effect of promoter architecture on the cell-to-cell variability in gene expression
According to recent experimental evidence, the architecture of a promoter,
defined as the number, strength and regulatory role of the operators that
control the promoter, plays a major role in determining the level of
cell-to-cell variability in gene expression. These quantitative experiments
call for a corresponding modeling effort that addresses the question of how
changes in promoter architecture affect noise in gene expression in a
systematic rather than case-by-case fashion. In this article, we make such a
systematic investigation, based on a simple microscopic model of gene
regulation that incorporates stochastic effects. In particular, we show how
operator strength and operator multiplicity affect this variability. We examine
different modes of transcription factor binding to complex promoters
(cooperative, independent, simultaneous) and how each of these affects the
level of variability in transcription product from cell-to-cell. We propose
that direct comparison between in vivo single-cell experiments and theoretical
predictions for the moments of the probability distribution of mRNA number per
cell can discriminate between different kinetic models of gene regulation.Comment: 35 pages, 6 figures, Submitte
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
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
First narrow-band search for continuous gravitational waves from known pulsars in advanced detector data
Spinning neutron stars asymmetric with respect to their rotation axis are potential sources of
continuous gravitational waves for ground-based interferometric detectors. In the case of known pulsars a
fully coherent search, based on matched filtering, which uses the position and rotational parameters
obtained from electromagnetic observations, can be carried out. Matched filtering maximizes the signalto-
noise (SNR) ratio, but a large sensitivity loss is expected in case of even a very small mismatch
between the assumed and the true signal parameters. For this reason, narrow-band analysis methods have
been developed, allowing a fully coherent search for gravitational waves from known pulsars over a
fraction of a hertz and several spin-down values. In this paper we describe a narrow-band search of
11 pulsars using data from Advanced LIGO’s first observing run. Although we have found several initial
outliers, further studies show no significant evidence for the presence of a gravitational wave signal.
Finally, we have placed upper limits on the signal strain amplitude lower than the spin-down limit for 5 of
the 11 targets over the bands searched; in the case of J1813-1749 the spin-down limit has been beaten for
the first time. For an additional 3 targets, the median upper limit across the search bands is below the
spin-down limit. This is the most sensitive narrow-band search for continuous gravitational waves carried
out so far
Constraints on the χ_(c1) versus χ_(c2) polarizations in proton-proton collisions at √s = 8 TeV
The polarizations of promptly produced χ_(c1) and χ_(c2) mesons are studied using data collected by the CMS experiment at the LHC, in proton-proton collisions at √s=8 TeV. The χ_c states are reconstructed via their radiative decays χ_c → J/ψγ, with the photons being measured through conversions to e⁺e⁻, which allows the two states to be well resolved. The polarizations are measured in the helicity frame, through the analysis of the χ_(c2) to χ_(c1) yield ratio as a function of the polar or azimuthal angle of the positive muon emitted in the J/ψ → μ⁺μ⁻ decay, in three bins of J/ψ transverse momentum. While no differences are seen between the two states in terms of azimuthal decay angle distributions, they are observed to have significantly different polar anisotropies. The measurement favors a scenario where at least one of the two states is strongly polarized along the helicity quantization axis, in agreement with nonrelativistic quantum chromodynamics predictions. This is the first measurement of significantly polarized quarkonia produced at high transverse momentum
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