A climatology of Sea‐viewing Wide Field‐of‐View Sensor (SeaWiFS) chlorophyll data over the Indian Ocean is used to examine the bloom variability patterns, identifying spatio‐temporal contrasts in ...bloom appearance and intensity and relating them to the variability of the physical environment. The near‐surface ocean dynamics is assessed using an ocean general circulation model (OGCM). It is found that over a large part of the basin, the seasonal cycle of phytoplankton is characterized by two consecutive blooms, one during the summer monsoon, and the other during the winter monsoon. Each bloom is described by means of two parameters, the timing of the bloom onset and the cumulated increase in chlorophyll during the bloom. This yields a regional image of the influence of the two monsoons on phytoplankton, with distinct regions emerging in summer and in winter. By comparing the bloom patterns with dynamical features derived from the OGCM (horizontal and vertical velocities and mixed‐layer depth), it is shown that the regional structure of the blooms is intimately linked with the horizontal and vertical circulations forced by the monsoons. Moreover, this comparison permits the assessment of some of the physical mechanisms that drive the bloom patterns, and points out the regions where these mechanisms need to be further investigated. A new outcome of this study is that in many distinct areas, time shifts of 1–2 months are witnessed in the timing of the bloom onsets in adjoining regions. These time shifts are rationalized in terms of horizontal advection and Rossby wave propagation.
Vegetation phenology is the study of the timing of seasonal events that are considered to be the result of adaptive responses to climate variations on short and long time scales. In the field of ...remote sensing of vegetation phenology, phenological metrics are derived from time series of optical data. For that purpose, considerable effort has been specifically focused on developing noise reduction and cloud-contaminated data removal techniques to improve the quality of remotely-sensed time series. Comparative studies between time series composed of satellite data acquired under clear and cloudy conditions and from radiometric data obtained with high accuracy from ground-based measurements constitute a direct and effective way to assess the operational use and limitations of remote sensing for predicting the main plant phenological events. In the present paper, we sought to explicitly evaluate the potential use of MODerate resolution Imaging Spectroradiometer (MODIS) remote sensing data for monitoring the seasonal dynamics of different types of vegetation cover that are representative of the major terrestrial biomes, including temperate deciduous forests, evergreen forests, African savannah, and crops. After cloud screening and filtering, we compared the temporal patterns and phenological metrics derived from in situ NDVI time series and from MODIS daily and 16-composite products. We also evaluated the effects of residual noise and the influence of data gaps in MODIS NDVI time series on the identification of the most relevant metrics for vegetation phenology monitoring. The results show that the inflexion points of a model fitted to a MODIS NDVI time series allow accurate estimates of the onset of greenness in the spring and the onset of yellowing in the autumn in deciduous forests (RMSE≤one week). Phenological metrics identical to those provided with the MODIS Global Vegetation Phenology product (MDC12Q2) are less robust to data gaps, and they can be subject to large biases of approximately two weeks or more during the autumn phenological transitions. In the evergreen forests, in situ NDVI time series describe the phenology with high fidelity despite small temporal changes in the canopy foliage. However, MODIS is unable to provide consistent phenological patterns. In crops and savannah, MODIS NDVI time series reproduce the general temporal patterns of phenology, but significant discrepancies appear between MODIS and ground-based NDVI time series during very localized periods of time depending on the weather conditions and spatial heterogeneity within the MODIS pixel. In the rainforest, the temporal pattern exhibited by a MODIS 16-day composite NDVI time series is more likely due to a pattern of noise in the NDVI data structure according to both rainy and dry seasons rather than to phenological changes. More investigations are needed, but in all cases, this result leads us to conclude that MODIS time series in tropical rainforests should be interpreted with great caution.
► We compare ground- and MODIS-based NDVI time-series in different terrestrial biomes. ► We identify the most relevant NDVI based vegetation phenological metrics. ► We develop a new method to quantify the uncertainty of the phenological metrics. ► In tropical rainforests, MODIS-derived phenology should be interpreted with caution.
•This ESO-ESMO ABC 5 Clinical Practice Guideline provides key recommendations for managing advanced breast cancer patients.•It provides updates on managing patients with all breast cancer subtypes, ...LABC, follow-up, palliative and supportive care.•Updated diagnostic and treatment algorithms are also provided.•All recommendations were compiled by a multidisciplinary group of international experts.•Recommendations are based on available clinical evidence and the collective expert opinion of the authors.
Phase transitions to quantum condensed phases--such as Bose-Einstein condensation (BEC), superfluidity, and superconductivity--have long fascinated scientists, as they bring pure quantum effects to a ...macroscopic scale. BEC has, for example, famously been demonstrated in dilute atom gas of rubidium atoms at temperatures below 200 nanokelvin. Much effort has been devoted to finding a solid-state system in which BEC can take place. Promising candidate systems are semiconductor microcavities, in which photons are confined and strongly coupled to electronic excitations, leading to the creation of exciton polaritons. These bosonic quasi-particles are 10(9) times lighter than rubidium atoms, thus theoretically permitting BEC to occur at standard cryogenic temperatures. Here we detail a comprehensive set of experiments giving compelling evidence for BEC of polaritons. Above a critical density, we observe massive occupation of the ground state developing from a polariton gas at thermal equilibrium at 19 K, an increase of temporal coherence, and the build-up of long-range spatial coherence and linear polarization, all of which indicate the spontaneous onset of a macroscopic quantum phase.
Background
Fish is one of the most allergenic foods. While clinical cross‐reactivity among different fishes is a widely accepted feature of fish allergy, associations with other food allergies are ...not well understood. This study aims at analyzing the relevance of clinical cross‐reactivity between fish and chicken meat in patients with allergy to chicken meat without sensitization to hen's eggs.
Methods
Patients with food allergy to fish and chicken meat (n = 29) or chicken meat only (n = 7) were recruited. IgE‐reactive chicken proteins were identified (Edman, MS analysis) and quantified (ELISA). Allergens were used in IgE ELISA and skin testing.
Results
Chicken parvalbumin and two new allergens, aldolase and enolase, were identified at 12, 40, and 50 kDa, respectively. They were recognized by sIgE of 61%, 75%, and 83% of all patient sera which were in the majority of the cases positive for the fish homologues as well. Fish and chicken meat allergens were highly cross‐reactive while high inhibition rates with fish or chicken allergens correlated with the patients' primary sensitization to fish or chicken. In cooked or roasted foods, enolase and aldolase were detectable in chicken breast while parvalbumin was detectable in chicken legs and wings.
Conclusions
Fish and chicken meat are cross‐reactive foods; both fish‐allergic and chicken meat‐allergic patients might be at risk of developing a food allergy to chicken meat or to fish, respectively. This clinical phenomenon is proposed to be termed ‘fish–chicken syndrome’ with cross‐reactive allergens involved being parvalbumins, enolases, and aldolases.
In the past years, mass univariate statistical analyses of neuroimaging data have been complemented by the use of multivariate pattern analyses, especially based on machine learning models. While ...these allow an increased sensitivity for the detection of spatially distributed effects compared to univariate techniques, they lack an established and accessible software framework. The goal of this work was to build a toolbox comprising all the necessary functionalities for multivariate analyses of neuroimaging data, based on machine learning models. The “Pattern Recognition for Neuroimaging Toolbox” (PRoNTo) is open-source, cross-platform, MATLAB-based and SPM compatible, therefore being suitable for both cognitive and clinical neuroscience research. In addition, it is designed to facilitate novel contributions from developers, aiming to improve the interaction between the neuroimaging and machine learning communities. Here, we introduce PRoNTo by presenting examples of possible research questions that can be addressed with the machine learning framework implemented in PRoNTo, and cannot be easily investigated with mass univariate statistical analysis.
Cancers with a defective DNA mismatch repair (dMMR) system contain thousands of mutations most frequently located in monomorphic microsatellites and are thereby defined as having microsatellite ...instability (MSI). Therefore, MSI is a marker of dMMR. MSI/dMMR can be identified using immunohistochemistry to detect loss of MMR proteins and/or molecular tests to show microsatellite alterations. Together with tumour mutational burden (TMB) and PD-1/PD-L1 expression, it plays a role as a predictive biomarker for immunotherapy.
To define best practices to implement the detection of dMMR tumours in clinical practice, the ESMO Translational Research and Precision Medicine Working Group launched a collaborative project, based on a systematic review-approach, to generate consensus recommendations on the: (i) definitions related to the concept of MSI/dMMR; (ii) methods of MSI/dMMR testing and (iii) relationships between MSI, TMB and PD-1/PD-L1 expression.
The MSI-related definitions, for which a consensus frame-work was used to establish definitions, included: ‘microsatellites’, ‘MSI’, ‘DNA mismatch repair’ and ‘features of MSI tumour’. This consensus also provides recommendations on MSI testing; immunohistochemistry for the mismatch repair proteins MLH1, MSH2, MSH6 and PMS2 represents the first action to assess MSI/dMMR (consensus with strong agreement); the second method of MSI/dMMR testing is represented by polymerase chain reaction (PCR)-based assessment of microsatellite alterations using five microsatellite markers including at least BAT-25 and BAT-26 (strong agreement). Next-generation sequencing, coupling MSI and TMB analysis, may represent a decisive tool for selecting patients for immunotherapy, for common or rare cancers not belonging to the spectrum of Lynch syndrome (very strong agreement). The relationships between MSI, TMB and PD-1/PD-L1 expression are complex, and differ according to tumour types.
This ESMO initiative is a response to the urgent questions raised by the growing success of immunotherapy and provides also important insights on the relationships between MSI, TMB and PD-1/PD-L1.
Patients with relapsed or refractory mantle-cell lymphoma who have disease progression during or after the receipt of Bruton's tyrosine kinase (BTK) inhibitor therapy have a poor prognosis. KTE-X19, ...an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, may have benefit in patients with relapsed or refractory mantle-cell lymphoma.
In a multicenter, phase 2 trial, we evaluated KTE-X19 in patients with relapsed or refractory mantle-cell lymphoma. Patients had disease that had relapsed or was refractory after the receipt of up to five previous therapies; all patients had to have received BTK inhibitor therapy previously. Patients underwent leukapheresis and optional bridging therapy, followed by conditioning chemotherapy and a single infusion of KTE-X19 at a dose of 2×10
CAR T cells per kilogram of body weight. The primary end point was the percentage of patients with an objective response (complete or partial response) as assessed by an independent radiologic review committee according to the Lugano classification. Per the protocol, the primary efficacy analysis was to be conducted after 60 patients had been treated and followed for 7 months.
A total of 74 patients were enrolled. KTE-X19 was manufactured for 71 patients and administered to 68. The primary efficacy analysis showed that 93% (95% confidence interval CI, 84 to 98) of the 60 patients in the primary efficacy analysis had an objective response; 67% (95% CI, 53 to 78) had a complete response. In an intention-to-treat analysis involving all 74 patients, 85% had an objective response; 59% had a complete response. At a median follow-up of 12.3 months (range, 7.0 to 32.3), 57% of the 60 patients in the primary efficacy analysis were in remission. At 12 months, the estimated progression-free survival and overall survival were 61% and 83%, respectively. Common adverse events of grade 3 or higher were cytopenias (in 94% of the patients) and infections (in 32%). Grade 3 or higher cytokine release syndrome and neurologic events occurred in 15% and 31% of patients, respectively; none were fatal. Two grade 5 infectious adverse events occurred.
KTE-X19 induced durable remissions in a majority of patients with relapsed or refractory mantle-cell lymphoma. The therapy led to serious and life-threatening toxic effects that were consistent with those reported with other CAR T-cell therapies. (Funded by Kite, a Gilead company; ZUMA-2 ClinicalTrials.gov number, NCT02601313.).
A spin torque magnetoresistive random access memory (ST-MRAM) holds great promise to be a fast, high density, nonvolatile memory that can enhance the performance of a variety of applications, ...particularly when used as a non-volatile buffer in data storage devices and systems. Towards that end, we have developed a fully functional 64 Mb DDR3 ST-MRAM built on 90 nm CMOS technology. The memory is organized in an 8-bank configuration that can sustain 1.6 GigaTransfers/s (DDR3-1600). We have run standard memory tests, such as a March6N pattern, on the full 64 Mb at 800 MHz with 0 fails for greater than 10 5 cycles. Full functionality was also verified from 0°C to 70°C with no significant change in performance. The bits are magnetic tunnel junctions (MTJs) having an MgO tunnel barrier and a magnetic free layer made of a CoFeB-based alloy with an in-plane magnetization, but with an out-of-plane anisotropy reduced by more than 50% due to an enhanced perpendicular surface anisotropy. To enable the 64 Mb performance, we developed an MTJ stack that has low switching voltage (V sw ), high breakdown voltage (V bd ), and excellent switching reliability with tight distributions. The ST switching distribution has σ ≈ 10%, and we found excellent agreement with a single Gaussian distribution down to an error rate . For our optimized material, the V sw /V bd ≈ 0.3, and the separation between V sw and V bd is ≈ 25σ. The energy barrier to magnetization reversal (E b ) was characterized using both time-dependent coercivity and higher temperature to accelerate reversal. We found the average E b ≈ 70kbT.
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