One of the most intriguing aspects of quantum mechanics is the impossibility of measuring at the same time observables corresponding to noncommuting operators, because of quantum uncertainty. This ...impossibility can be partially relaxed when considering joint or sequential weak value evaluation. Indeed, weak value measurements have been a real breakthrough in the quantum measurement framework that is of the utmost interest from both a fundamental and an applicative point of view. In this Letter, we show how we realized for the first time a sequential weak value evaluation of two incompatible observables using a genuine single-photon experiment. These (sometimes anomalous) sequential weak values revealed the single-operator weak values, as well as the local correlation between them.
Tumor phenotype may change during breast cancer progression. This study evaluates the prognostic impact of receptor discordance between paired primaries and recurrences.
One hundred and thirty-nine ...patients underwent histological sampling of suspected breast cancer recurrence. All the pathology assessments ER, PgR and human epidermal growth factor receptor 2 (HER2) on both primaries and confirmed recurrences were performed at the same laboratory.
A breast cancer recurrence was confirmed in 119 cases. Rates of discordance were 13.4%, 39% and 11.8% for ER, PgR and HER2, respectively. Ninety-two patients maintained the same tumor phenotype i.e. the same hormone receptors (HR) and HER2 status, whereas 27 (22.7%) changed during progression. The loss of HR positivity and the loss of HER2 positivity resulted in a worse post-recurrence survival (P=0.01 and P=0.008, respectively) and overall survival (OS; P=0.06 and P=0.0002, respectively), compared with the corresponding concordant-positive cases. Tumor phenotype discordance was associated with worse post-recurrence and OS (P=0.006 and P=0.002, respectively); those cases who turned into triple-negative experienced the poorest outcome, respect to the concordant group (P=0.001, OS).
We demonstrated for the first time an impact on OS of phenotype discordance between primary breast cancer and relapse. Among discordant cases, receptor loss resulted in the main determinant of poorer outcome.
Weak value measurements have recently given rise to a great amount of interest in both the possibility of measurement amplification and the chance for further quantum mechanics foundations ...investigation. In particular, a question emerged about weak values being proof of the incompatibility between quantum mechanics and noncontextual hidden variables theories (NCHVTs). A test to provide a conclusive answer to this question was given by Pusey Phys. Rev. Lett. 113, 200401 (2014), where a theorem was derived showing the NCHVT incompatibility with the observation of anomalous weak values under specific conditions. In this Letter we realize this proposal, clearly pointing out the connection between weak values and the contextual nature of quantum mechanics.
Emerging literature data are showing that a change in human epidermal growth factor receptor (HER2) status adversely affects breast cancer patient's prognosis. The aim of this study was to evaluate ...the prognostic impact of HER2 loss in patients with HER2-positive disease treated with neoadjuvant therapy with or without anti-HER2 agents.
One hundred and seven consecutive HER2-positive patients were identified from a prospectively maintained database. The first cohort includes 40 patients treated with chemotherapy (CT) alone. The second cohort includes 67 patients treated with neoadjuvant CT plus anti-HER2 agents (trastuzumab and/or lapatinib). HER2 expression was evaluated by immunihistochemistry or fluorescence in situ hybridization on pretreatment core biopsy and on surgical specimen after therapy.
The rates of pathologic complete response (pCR) and breast-conserving surgery were higher in the CT + anti-HER2 cohort. A loss of HER2 expression was observed in 40% of the patients with residual disease after CT alone versus 14.7% of the patients after CT + anti-HER2 agents (P = 0.019). Patients not achieving a pCR have a significant increase in the risk of relapse when compared with those achieving a pCR (hazard ratio HR 9.55, P = 0.028). Patients with HER2 loss tended to have a higher risk of relapse as comparing to patients with maintained HER2 positivity (HR 2.41, P = 0.063).
The pCR is confirmed as a powerful predictor of long-term outcome. The rate of HER2 loss is higher in patients receiving neoadjuvant CT without anti-HER2 agents. HER2 status on residual disease after preoperative therapy can be helpful in selecting patients at different risk of relapse, to be included in prospective trial exploring further adjuvant therapy.
Data reduction pipeline for the Hi-GAL survey Traficante, A.; Calzoletti, L.; Veneziani, M. ...
Monthly Notices of the Royal Astronomical Society,
October 2011, Letnik:
416, Številka:
4
Journal Article
Recenzirano
Odprti dostop
We present the data reduction pipeline for the Herschel Infrared Galactic Plane survey (Hi-GAL). Hi-GAL is a key project of the Herschel satellite, which is mapping the inner part of the Galactic ...plane (|l| ≤ 70° and |b| ≤ 1°), using two Photodetector Array Camera and Spectrometer (PACS) and three Spectral and Photometric Imaging Receiver (SPIRE) frequency bands, from 70 to 500 μm. Our pipeline relies only partially on the Herschel Interactive Processing Environment (hipe). It features several newly developed routines to perform data reduction, including accurate data culling, noise estimation and minimum variance map-making, the latter performed with the romagal algorithm, a deep modification of the roma code already tested on cosmological surveys. We discuss in depth the properties of the Hi-GAL science demonstration phase data.
We have observed the Andromeda galaxy, Messier 31 (M31), at 6.7 GHz with the Sardinia Radio Telescope. We mapped the radio emission in the C-band, re-analyzed WMAP and Planck maps, as well as other ...ancillary data, and we have derived an overall integrated flux density spectrum from the radio to the infrared. This allowed us to estimate the emission budget from M31. Integrating over the whole galaxy, we found strong and highly significant evidence for anomalous microwave emission (AME), at the level of Jy at the peaking frequency of 25 GHz. Decomposing the spectrum into known emission mechanisms such as free-free, synchrotron, thermal dust, and AME arising from electric dipole emission from rapidly rotating dust grains, we found that the overall emission from M31 is dominated, at frequencies below 10 GHz, by synchrotron emission with a spectral index of , with subdominant free-free emission. At frequencies 10 GHz, AME has a similar intensity to that of synchrotron and free-free emission, overtaking them between 20 and 50 GHz, whereas thermal dust emission dominates the emission budget at frequencies above 60 GHz, as expected.
The aim of this work was to evaluate the impact of (and relative contribution of) tumor-related and immune-related diversity of HER2-positive disease on the response to neoadjuvant chemotherapy plus ...anti-HER2 agents.
The CherLOB phase II study randomized 121 HER2-positive breast cancer patients to neoadjuvant chemotherapy plus trastuzumab, lapatinib or both. Tumor samples from diagnostic core biopsy were centralized. Tumor-infiltrating lymphocytes (TILs) were evaluated on H&E slides. Intrinsic subtyping was carried out using the research-based 50-gene prediction analysis of a microarray (PAM50) subtype predictor. Immune-related gene signatures were also evaluated.
Continuous Str-TILs and It-TILs were significantly associated with pCR OR 1.03, 95% CI 1.02–1.05 (P < 0.001) and OR 1.09, 95% CI 1.04–1.15 (P < 0.001) for Str-TILs and It-TILs, respectively. According to PAM50, the subtype distribution was as follows: HER2-enriched 26.7%, Luminal A 25.6%, Luminal B 16.3%, Basal-like 14% and Normal-like 17.4%. The highest rate of pCR was observed for the HER2-enriched subtype (50%), followed by Basal-like, Luminal B and Luminal A (χ2 test, P = 0.026). Immune gene signatures significantly associated with pCR in univariate analyses were identified: most of them maintained a significant association with pCR in multivariate analyses corrected for PAM50 subtypes, whereas TILs did not.
In this study, both tumor-related and immune-related features contribute to the modulation of pCR after neoadjuvant chemotherapy plus anti-HER2 agents. Immune signatures rather than TILs added significant prediction of pCR beyond PAM50 intrinsic subtypes.
We study the propagation of a specific class of instrumental systematics to the reconstruction of the
B
-mode power spectrum of the cosmic microwave background (CMB). We focus on the non-idealities ...of the half-wave plate (HWP), a polarization modulator that is to be deployed by future CMB experiments, such as the phase-A satellite mission LiteBIRD. We study the effects of non-ideal HWP properties, such as transmittance, phase shift, and cross-polarization. To this end, we developed a simple, yet stand-alone end-to-end simulation pipeline adapted to LiteBIRD. We analyzed the effects of a possible mismatch between the measured frequency profiles of HWP properties (used in the mapmaking stage of the pipeline) and the actual profiles (used in the sky-scanning step). We simulated single-frequency, CMB-only observations to emphasize the effects of non-idealities on the BB power spectrum. We also considered multi-frequency observations to account for the frequency dependence of HWP properties and the contribution of foreground emission. We quantified the systematic effects in terms of a bias Δ
r
on the tensor-to-scalar ratio,
r
, with respect to the ideal case without systematic effects. We derived the accuracy requirements on the measurements of HWP properties by requiring Δ
r
< 10
−5
(1% of the expected LiteBIRD sensitivity on
r
). Our analysis is introduced by a detailed presentation of the mathematical formalism employed in this work, including the use of the Jones and Mueller matrix representations.
There is the need to identify new prognostic markers to refine risk stratification for HER2-positive early breast cancer patients. The aim of this study was to evaluate the association of ...tumor-infiltrating lymphocytes (TILs) with distant disease-free survival (DDFS) in patients with HER2-positive early breast cancer enrolled in the ShortHER adjuvant trial which compared 9 weeks versus 1-year trastuzumab in addition to chemotherapy, and to test the interaction between TILs and treatment arm.
Stromal TILs were assessed for 866 cases on centralized hematoxylin and eosin-stained tumor slides. The association of TILs as 10% increments with DDFS was assessed with Cox models. Kaplan–Meier curves were estimated for patients with TILs ≥20% and TILs <20%. Median follow-up was 6.1 years.
Median TILs was 5% (Q1–Q3 1%–15%). Increased TILs were independently associated with better DDFS in multivariable model hazard ratio (HR) 0.73, 95% confidence interval (CI) 0.59–0.89, P = 0.006, for each 10% TILs increment. Five years DDFS rates were 91.1% for patients with TILs <20% and 95.7% for patients with TILs ≥20% (P = 0.025). The association between 10% TILs increments and DDFS was significant for patients randomized to 9 weeks of trastuzumab (HR 0.60, 95% CI 0.41–0.88) but not for patients treated with 1 year of trastuzumab (HR 0.89, 95% CI 0.71–1.12; test for interaction P = 0.088). For patients with TILs <20%, the HR for the comparison between the short versus the long arm was 1.75 (95% CI 1.09–2.80, P=0.021); whereas, for patients with TILs ≥20% the HR for the comparison of short versus long arm was 0.23 (95% CI 0.05–1.09, P = 0.064), resulting in a significant interaction (P = 0.015).
TILs are an independent prognostic factor for HER2-positive early breast cancer patients treated with adjuvant chemotherapy and trastuzumab and may refine the ability to identify patients at low risk of relapse eligible for de-escalated adjuvant therapy.
The original central fatigue hypothesis suggested that an exercise-induced increase in extracellular serotonin concentrations in several brain regions contributed to the development of fatigue during ...prolonged exercise. Serotonin has been linked to fatigue because of its well known effects on sleep, lethargy and drowsiness and loss of motivation. Several nutritional and pharmacological studies have attempted to manipulate central serotonergic activity during exercise, but this work has yet to provide robust evidence for a significant role of serotonin in the fatigue process. However, it is important to note that brain function is not determined by a single neurotransmitter system and the interaction between brain serotonin and dopamine during prolonged exercise has also been explored as having a regulative role in the development of fatigue. This revised central fatigue hypothesis suggests that an increase in central ratio of serotonin to dopamine is associated with feelings of tiredness and lethargy, accelerating the onset of fatigue, whereas a low ratio favours improved performance through the maintenance of motivation and arousal. Convincing evidence for a role of dopamine in the development of fatigue comes from work investigating the physiological responses to amphetamine use, but other strategies to manipulate central catecholamines have yet to influence exercise capacity during exercise in temperate conditions. Recent findings have, however, provided support for a significant role of dopamine and noradrenaline (norepinephrine) in performance during exercise in the heat. As serotonergic and catecholaminergic projections innervate areas of the hypothalamus, the thermoregulatory centre, a change in the activity of these neurons may be expected to contribute to the control of body temperature whilst at rest and during exercise. Fatigue during prolonged exercise clearly is influenced by a complex interaction between peripheral and central factors.
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