The learning of new words is a challenge that accompanies human beings throughout the entire life span. Although the main electrophysiological markers of word learning have already been described, ...little is known about the performance-dependent neural machinery underlying this exceptional human faculty. Furthermore, it is currently unknown how word learning abilities are related to verbal memory capacity, auditory attention functions, phonetic discrimination skills, and musicality. Accordingly, we used EEG and examined 40 individuals, who were assigned to two groups (low LPs and high performers HPs) based on a median split of word learning performance, while they completed a phonetic-based word learning task. Furthermore, we collected behavioral data during an attentive listening and a phonetic discrimination task with the same stimuli to address relationships between auditory attention and phonetic discrimination skills, word learning performance, and musicality. The phonetic-based word learning task, which also included a nonlearning control condition, was sensitive enough to segregate learning-specific and unspecific N200/N400 manifestations along the anterior–posterior topographical axis. Notably, HPs exhibited enhanced verbal memory capacity and we also revealed a performance-dependent spatial N400 pattern, with maximal amplitudes at posterior electrodes in HPs and central maxima in LPs. Furthermore, phonetic-based word learning performance correlated with verbal memory capacity and phonetic discrimination skills, whereas the latter was related to musicality. This experimental approach clearly highlights the multifaceted dimensions of phonetic-based word learning and is helpful to disentangle learning-specific and unspecific ERPs.
Anderson localization is the ubiquitous phenomenon of inhibition of transport of classical and quantum waves in a disordered medium. In dimension one, it is well known that all states are localized, ...implying that the distribution of an initially narrow wave packet released in a disordered potential will, at long time, decay exponentially on the scale of the localization length. However, the exact shape of the stationary localized distribution differs from a purely exponential profile and has been computed almost fifty years ago by Gogolin. Using the atomic quantum kicked rotor, a paradigmatic quantum simulator of Anderson localization physics, we study this asymptotic distribution by two complementary approaches. First, we discuss the connection of the statistical properties of the system’s localized eigenfunctions and their exponential decay with the localization length of the Gogolin distribution. Next, we make use of our experimental platform, realizing an ideal Floquet disordered system, to measure the long-time probability distribution and highlight the very good agreement with the analytical prediction compared to the purely exponential one over 3 orders of magnitude.
Graphical Abstract
Abstract
Following the results of the IMpassion130 trial, an early access program (EAP) was opened in France, allowing patients with PD-L1-positive advanced triple negative breast cancer (aTNBC) to ...receive a combination of paclitaxel and atezolizumab as first line therapy. This EAP was later discontinued when the IMpassion131 trial read out with negative results. We performed a retrospective multicentric analysis in patients who were prospectively enrolled in the French EAP. Efficacy and toxicity data were obtained on 64 patients treated from August 2019 to August 2020 in 10 French cancer centers. Median progression-free survival (PFS) and overall survival (OS) were 4.1 months (95% CI 3.0–5.8) and 17.9 months (95% CI 12.4–NR), respectively. The 6-months PFS rate was 28% (95% CI 16–40%) (N = 18/64), while N = 33/64 patients (52%, 95% CI 38–63%) experienced a tumor response. Exploratory subgroup analyses retrieved that corticosteroid use at inclusion in the EAP, before treatment initiation, was the only independent unfavorable prognostic factor for PFS (HR 2.7, 95% CI 1.3–5.6). No new safety signal was observed. This real-life study, unique by its setting (EAP granted by anticipation and later withdrawn), suggests atezolizumab and paclitaxel has a limited efficacy in PD-L1-positive aTNBC, especially in patients receiving corticosteroids as comedication before treatment start.
Building upon the exact methods presented in our earlier work (2022) 5, we introduce a heuristic approach for the star discrepancy subset selection problem. The heuristic gradually improves the ...current-best subset by replacing one of its elements at a time. While it does not necessarily return an optimal solution, we obtain promising results for all tested dimensions. For example, for moderate sizes 30≤n≤240, we obtain point sets in dimension 6 with L∞ star discrepancy up to 35% better than that of the first n points of the Sobol' sequence. Our heuristic works in all dimensions, the main limitation being the precision of the discrepancy calculation algorithms. We provide a comparison with an energy functional introduced by Steinerberger (2019) 31, showing that our heuristic performs better on all tested instances. Finally, our results give further empirical information on inverse star discrepancy conjectures.
Learning a new language requires the identification of word units from continuous speech (the speech segmentation problem) and mapping them onto conceptual representation (the word to world mapping ...problem). Recent behavioral studies have revealed that the statistical properties found within and across modalities can serve as cues for both processes. However, segmentation and mapping have been largely studied separately, and thus it remains unclear whether both processes can be accomplished at the same time and if they share common neurophysiological features. To address this question, we recorded EEG of 20 adult participants during both an audio alone speech segmentation task and an audiovisual word-to-picture association task. The participants were tested for both the implicit detection of online mismatches (structural auditory and visual semantic violations) as well as for the explicit recognition of words and word-to-picture associations. The ERP results from the learning phase revealed a delayed learning-related fronto-central negativity (FN400) in the audiovisual condition compared to the audio alone condition. Interestingly, while online structural auditory violations elicited clear MMN/N200 components in the audio alone condition, visual-semantic violations induced meaning-related N400 modulations in the audiovisual condition. The present results support the idea that speech segmentation and meaning mapping can take place in parallel and act in synergy to enhance novel word learning.
Invasive lobular carcinomas (ILCs) have a low frequency of ERBB2 amplification, therefore restricting the use of conventional anti-HER2 therapies for this histologic special type. Conversely, ILCs ...with low HER2 overexpression may represent a broader target for the use of emerging antibody drug conjugate therapies targeting HER2, since these treatments have proven effective in HER2-low breast cancers. Very scarce data about HER2-low ILCs have been so far published, although these tumors could have different prevalence and histomolecular specificities compared with invasive breast carcinoma of no special type (IBC-NST). Our aims in that context were to decipher the clinicopathological and molecular features of a large series of HER2-low ILCs. Comparative evaluation of HER2-low prevalence was done based on a retrospective series of 7970 patients from Institut Curie, with either primary invasive lobular (N = 1103) or no special type (N = 6867) invasive carcinoma. Clinicopathological and molecular analyses of HER2-zero, HER2-low, and HER2-positive ILCs were performed on a subgroup of 251 patients who underwent surgery for a primary ILC between 2005 and 2008. The mutational profile of these 251 cases was determined from RNAseq data. Compared with HER2-negative IBC-NSTs, the HER2-negative ILCs were found to display a higher frequency of HER2-zero cases (59.4% vs 53.7%) and a lower frequency of HER2-low (40.6% vs 46.3%) (P < .001). Clinicopathological features associated with HER2-low status (vs HER2-zero) in ILC were older age, postmenopausal status, nonclassic ILC histological types, higher grade, proliferation, and estrogen receptor expression levels. Survival curve analysis showed a significantly lower risk of local recurrence for HER2-low (vs HER2-zero) ILCs, but no association was found between HER2 status and either breast cancer-specific survival or distant metastasis-free interval. ERBB3 was the unique mutated gene exclusively associated with HER2-low ILCs yet being mutated at a low frequency (7.1%) (false discovery rate < 0.05). In conclusion, HER2-low ILCs exhibit their own particularities, both on clinical-pathological and molecular levels. Our findings call for larger multicenter validation studies.
The choice between chemotherapy and endocrine therapy as first-line treatment for hormone receptor-positive, ERBB2 (also known as HER2)-negative metastatic breast cancer is usually based on the ...presence of clinical features associated with a poor prognosis. In this setting, a high circulating tumor cell (CTC) count (≥5 CTCs/7.5 mL) is a strong adverse prognostic factor for overall survival and progression-free survival (PFS).
To compare the efficacy of a clinician-driven treatment choice vs a CTC-driven choice for first-line treatment.
In the CTC arm, patients received chemotherapy or endocrine therapy according to the CTC count (chemotherapy if ≥5 CTCs/7.5 mL; endocrine therapy if <5 CTCs/7.5 mL), whereas in the control arm, the choice was left to the investigator.
In the STIC CTC randomized, open-label, noninferiority phase 3 trial, participants were randomized to a clinician-driven choice of first-line treatment or a CTC count-driven first-line treatment choice. Eligible participants were premenopausal and postmenopausal women 18 years or older diagnosed with hormone receptor-positive, ERBB2-negative metastatic breast cancer. Data were collected at 17 French cancer centers from February 1, 2012, to July 28, 2016, and analyzed June 2019 to October 2019.
The primary end point was the investigator-assessed PFS in the per-protocol population, with a noninferiority margin of 1.25 for the 90% CI of the hazard ratio.
Among the 755 women in the per-protocol population, the median (range) age was 63 (30-88) years 64 (30-88) years for the 377 patients allocated to the CTC arm and 63 (31-87) years for the 378 patients allocated to the standard arm; 138 (37%) and 103 (27%) received chemotherapy, respectively. Median PFS was 15.5 months (95% CI, 12.7-17.3) in the CTC arm and 13.9 months (95% CI, 12.2-16.3) in the standard arm. The primary end point was met, with a hazard ratio of 0.94 (90% CI, 0.81-1.09).
This randomized clinical trial found that the CTC count may be a reliable biomarker method for guiding the choice between chemotherapy and endocrine therapy as the first-line treatment in hormone receptor-positive, ERBB2-negative metastatic breast cancer.
ClinicalTrials.gov Identifier: NCT01710605.
The atomic Quantum Kicked Rotor (QKR) is an outstanding 'quantum simulator' for the exploration of transport in disordered quantum systems. Here we study experimentally the phase-shifted QKR, which ...we show to display properties close to an ideal disordered quantum system, opening new windows into the study of Anderson physics.
.In patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer, the STIC CTC trial established that, for choosing between endocrine therapy (ET) ...or chemotherapy, the use of circulating tumor cell (CTC) count is noninferior to the investigator's choice in terms of progression-free survival. Here, we report overall survival (OS) results, a secondary end point. Patients were randomly assigned in a 1:1 ratio to have their first-line treatment (ET or chemotherapy) determined by investigators or CTC count (chemotherapy if ≥ 5 CTCs/7.5 mL; ET if low CTC count; CellSearch). OS was assessed at the discontinuation of follow-up. After a median follow-up of 4.7 years, 382 deaths (50.6%) had occurred among 755 patients. Median OS was 51.3 months (95% CI, 46.8 to 55.1) in the CTC arm and 45.5 months (95% CI, 40.9 to 51.1) in the standard arm (hazard ratio HR for death, 0.85; 95% CI, 0.69 to 1.03;
= .11). Among 189 patients (25.0%) with ET recommended by clinicians and high CTC count, chemotherapy was superior to ET (HR for death, 0.53; 95% CI, 0.36 to 0.78;
= .001). In case of a discordant estimate, OS data demonstrate the clinical utility of CTC count.
In the last decade, several studies have investigated the neuroplastic changes induced by long-term musical training. Here we investigated structural brain differences in expert pianists compared to ...non-musician controls, as well as the effect of the age of onset (AoO) of piano playing. Differences with non-musicians and the effect of sensitive periods in musicians have been studied previously, but importantly, this is the first time in which the age of onset of music-training was assessed in a group of musicians playing the same instrument, while controlling for the amount of practice. We recruited a homogeneous group of expert pianists who differed in their AoO but not in their lifetime or present amount of training, and compared them to an age-matched group of non-musicians. A subset of the pianists also completed a scale-playing task in order to control for performance skill level differences. Voxel-based morphometry analysis was used to examine gray-matter differences at the whole-brain level. Pianists showed greater gray matter (GM) volume in bilateral putamen (extending also to hippocampus and amygdala), right thalamus, bilateral lingual gyri and left superior temporal gyrus, but a GM volume shrinkage in the right supramarginal, right superior temporal and right postcentral gyri, when compared to non-musician controls. These results reveal a complex pattern of plastic effects due to sustained musical training: a network involved in reinforcement learning showed increased GM volume, while areas related to sensorimotor control, auditory processing and score-reading presented a reduction in the volume of GM. Behaviorally, early-onset pianists showed higher temporal precision in their piano performance than late-onset pianists, especially in the left hand. Furthermore, early onset of piano playing was associated with smaller GM volume in the right putamen and better piano performance (mainly in the left hand). Our results, therefore, reveal for the first time in a single large dataset of healthy pianists the link between onset of musical practice, behavioral performance, and putaminal gray matter structure. In summary, skill-related plastic adaptations may include decreases and increases in GM volume, dependent on an optimization of the system caused by an early start of musical training. We believe our findings enrich the plasticity discourse and shed light on the neural basis of expert skill acquisition.
•We scanned and compared 36 professional pianists and 17 non-musicians.•Pianists, differing in the age of onset of training, performed a scale-playing task.•Musicianship elicited a pattern of increases and decreases of gray matter.•Piano performance was better in early-onset pianists, especially in the left hand.•The earlier the onset the smaller the amount of gray matter in the right putamen.
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