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SARS-CoV-2 Omicron variant has been characterized by decreased clinical severity, raising the question of whether early variant-specific interactions within the mucosal surfaces of the respiratory tract could mediate its attenuated pathogenicity. Here, we employed ex vivo infection of native human nasal and lung tissues to investigate the local-mucosal susceptibility and innate immune response to Omicron, compared to Delta and earlier SARS-CoV-2 variants of concern (VOC). We show that the replication of Omicron in lung tissues is highly restricted compared to other VOC, whereas it remains relatively unchanged in nasal tissues. Mechanistically, Omicron induced a much stronger antiviral interferon response in infected tissues compared to Delta and earlier VOC - a difference which was most striking in the lung tissues, where the innate immune response to all other SARS-CoV-2 VOC was blunted. Our data provide new insights to the reduced lung involvement and clinical severity of Omicron.

The MICROSCOPE mission was designed to test the weak equivalence principle (WEP), stating the equality between the inertial and the gravitational masses, with a precision of 10^{-15} in terms of the Eötvös ratio η. Its experimental test consisted of comparing the accelerations undergone by two collocated test masses of different compositions as they orbited the Earth, by measuring the electrostatic forces required to keep them in equilibrium. This was done with ultrasensitive differential electrostatic accelerometers onboard a drag-free satellite. The mission lasted two and a half years, cumulating five months worth of science free-fall data, two-thirds with a pair of test masses of different compositions-titanium and platinum alloys-and the last third with a reference pair of test masses of the same composition-platinum. We summarize the data analysis, with an emphasis on the characterization of the systematic uncertainties due to thermal instabilities and on the correction of short-lived events which could mimic a WEP violation signal. We found no violation of the WEP, with the Eötvös parameter of the titanium and platinum pair constrained to η(Ti,Pt)=[-1.5±2.3(stat)±1.5(syst)]×10^{-15} at 1σ in statistical errors.

Documenting the preparation phase of giant earthquakes and retrieving pre-seismic signals of upcoming events is a crucial challenge. Over the short term, various deformation transients have been detected before large subduction events, emphasizing in particular the role of the slab pull in driving plate motions (e.g., Bouchon et al., 2016 ; Bedford et al., 2020). Among them, we previously evidenced an anomalous gravity gradient signal during the months before the March 2011 Tohoku earthquake, likely originating from the solid Earth (Panet et al., 2018). We showed that it could reflect a broad deformation of the subducted slab prior to the event, generating the giant earthquake as the deformation propagated from depth to surface.Taking the example of the 2011 Tohoku earthquake, we conduct here a systematic and global retrospective analysis of time series of GRACE-reconstructed gravity gradients truncated in February 2011. Our aim is to test whether the gravity gradient variations preceeding the earthquake can be identified as singular and potentially originating from the solid Earth in an automated way and without knowledge on the upcoming event. First, we enhance the angular resolution of the gravity gradients in order to extract signals closely aligned with a chosen plate boundary orientation. Along this preferred orientation, we extract fast temporal variations at the sub-annual timescales of geodetic, gravitational and seismic signals reported before the event in previous studies. To evaluate the significance of the obtained gravity gradient anomalies, we design a method to extract coherent signals between different GRACE gravity field models and assess their sensitivity to the dealiasing ocean model. We present and discuss the results of these analyses applied to different sets of GRACE gravity models: the GRGS03, GRGS04 and CSR06 solutions, as well as their respective ocean dealiasing models. Beyond the case of the Tohoku earthquake, our approach can be applied to the systematic monitoring of the Pacific subduction belt, to detect gravity variations potentially linked with sudden changes in slab motions in-depth these plate boundaries. ReferencesBedford, J. R., et al. (2020). Months-long thousand-kilometre-scale wobbling before great subduction earthquakes, Nature 580, 628-635.Bouchon, M., et al. (2016). Potential slab deformation and plunge prior to the Tohoku, Iquique and Maule earthquakes, Nature Geoscience 9, 380-383.Panet, I., et al. (2018). Migrating pattern of deformation prior to the Tohoku-Oki earthquake revealed by GRACE data, Nature Geoscience 11, 367-373.

The control on megathrust earthquake generation exerted by deeper subduction processes remains poorly understood and still insufficiently documented. Here, we use the 2003-2014 space-time variations of the Earth’s gravity gradients derived from the GRACE geoids in order to probe aseismic mass variations at depth and their possible interactions with intraplate seismicity along the Chilean margin. We work with three different datasets of GRACE geoid models over a large region surrounding the rupture zone of the Mw 8.8 2010 Maule earthquake. In order to separate signals associated with mass sources of differents sizes, shapes or orientations, we reconstruct each month the Earth’s gravity gradients at different spatial scales from these geoid models. Our analysis emphasizes a highly anomalous, large-amplitude gravity gradients signal that appears three months prior to the earthquake North of the epicentral zone, and progressively increases until the megathrustal rupture, in all three datasets. We show that this large signal cannot be caused by a shallow hydrological source nor by GRACE striping artefacts and dealiasing models. Instead, we conclude that its most likely origin is in mass redistributions within the solid Earth on the continental side of the subduction zone. These anomalous gravity gradient variations could be explained by a deep extensional deformation of the slab around 150-km depth along the Nazca Plate subduction direction, driving large-scale fluid motion in the subduction zone and into the overriding lithosphere. Our results highlight the importance of observations of the Earth’s time-varying gravity field from satellites to probe aseismic mass redistributions in-depth major plate boundaries . The detection of such mass redistributions at depth by GRACE and their interactions with interplate seismicity opens a new field of research to better characterize and understand the dynamics of the seismic cycle at megathrusts.

Nos últimos anos, o Direito à Cidade entra como forte pauta na agenda dos Direitos Humanos, no contexto acadêmico e de lutas sociais. Decorrem sobre ele o acesso com qualidade à saúde, educação, segurança pública, cultura, transporte e lazer. Entretanto, a realidade para muitos indivíduos, tidos como minorias de poder, é a violação de direitos e sua exposição à diversos tipos de violência. Dentre esses indivíduos estão aqueles que representam a comunidade LGBT+, que, ao romper com o padrão cisheteronormativo de gênero e sexualidade são expostos, além das agressões em geral, à coibição do direito de se expressarem no espaço urbano. Tal prática acaba por promover um processo de territorialização com a eleição de espaços urbanos propícios ao exercício livre de suas condições de existência, dentre elas, a prática do lazer. Essa pesquisa tem como objetivo relatar, apresentar e discutir os resultados de uma investigação que teve lugar na cidade de João Pessoa, sobre o

BACKGROUND: Phase 2 cooperative group meningioma trial assessing the safety and efficacy of risk-adaptive management strategies. This is the initial analysis of the high-risk cohort. METHODS AND MATERIALS: High-risk patients were those with a new or recurrent World Health Organization (WHO) grade III meningioma of any resection extent, recurrent WHO grade II of any resection extent, or new WHO grade II after subtotal resection. Patients received intensity-modulated radiotherapy (IMRT) using a simultaneous integrated boost technique (60 Gy high dose and 54 Gy low dose in 30 fractions). Three-year progression-free survival (PFS) was the primary endpoint. Adverse events (AEs) were scored per NCI Common Terminology Criteria for Adverse Events version 3. RESULTS: Of 57 enrolled patients, 53 received protocol treatment. Median follow-up was 4.0 years (4.8 years for living patients). Two patients withdrew without progression before year 3; for the remaining 51 patients, 3-year PFS was 58.8%. Among all 53 protocol-treated patients, 3-year PFS was 59.2%. Three-year local control was 68.9%, and overall survival was 78.6%. Of 51 patients, 1 patient (1.9%) experienced a late grade-5 necrosis-related AE. All other acute (23 of 53 patients) and late (21 of 51 patients) AEs were grades 1 to 3. CONCLUSIONS: Patients with high-risk meningioma treated with IMRT (60 Gy/30) experienced 3-year PFS of 58.8%. Combined acute and late AEs were limited to grades 1 to 3, except for a single necrosis-related grade 5 event. These results support postoperative IMRT for high-risk meningioma and invite ongoing investigations to improve outcomes further. © 2019 Elsevier Inc. All rights reserved.

The MICROSCOPE mission was designed to test the Weak Equivalence Principle (WEP), stating the equality between the inertial and the gravitational masses, with a precision of $10^{-15}$ in terms of the E\"otv\"os ratio $\eta$. Its experimental test consisted of comparing the accelerations undergone by two collocated test masses of different compositions as they orbited the Earth, by measuring the electrostatic forces required to keep them in equilibrium. This was done with ultra-sensitive differential electrostatic accelerometers onboard a drag-free satellite. The mission lasted two and a half years, cumulating five-months-worth of science free-fall data, two thirds with a pair of test masses of different compositions -- Titanium and Platinum alloys -- and the last third with a reference pair of test masses of the same composition -- Platinum. We summarize the data analysis, with an emphasis on the characterization of the systematic uncertainties due to thermal instabilities and on the correction of short-lived events which could mimic a WEP violation signal. We found no violation of the WEP, with the E\"otv\"os parameter of the Titanium and Platinum pair constrained to $\eta({\rm Ti, Pt})~=~ [-1.5 \pm 2.3~{\rm (stat)} \pm 1.5~{\rm (syst)}]~\times 10^{-15}$ at $1\sigma$ in statistical errors., Comment: Phys. Rev. Lett. 129, 121102

O processo projetual que obteve como produto final o anteprojeto de uma Unidade Básica de Saúde, localizada na cidade de Belém (PA), foi resultado de uma experiência acadêmica de interdisciplinaridade e colaboração mútua com os alunos do quarto período do curso de Arquitetura e Urbanismo da Universidade Federal de Campina Grande – CAU/UFCG, a partir da integração entre as disciplinas de Projeto de Arquitetura II (PA II), Planejamento da Paisagem I (PP I) e Conforto Ambiental II (CA II). As metodologias aplicadas às disciplinas, como: avaliação pós ocupação (APO), estudo de projetos correlatos e a consultoria de especialistas - contribuíram não apenas para a concepção projetual, como, também, para o incentivo do senso crítico e questionador acerca do espaço e de suas respectivas apropriações. Ao final do processo foram selecionadas três propostas para representar o CAU/UFCG no concurso estudantil íbero-americano de arquitetura bioclimática na XI Bienal José Miguel Aroztegui, que ocorreu durante o ENCAC/ELACAC na cidade de João Pessoa/PB. O anteprojeto da Unidade Básica de Saúde intitulada “UBS Rio Guamá” foi selecionado como menção honrosa

Summary Background Whole breast irradiation delivered once per day over 3–5 weeks after breast conserving surgery reduces local recurrence with good cosmetic results. Accelerated partial breast irradiation (APBI) delivered over 1 week to the tumour bed was developed to provide a more convenient treatment. In this trial, we investigated if external beam APBI was non-inferior to whole breast irradiation. Methods We did this multicentre, randomised, non-inferiority trial in 33 cancer centres in Canada, Australia and New Zealand. Women aged 40 years or older with ductal carcinoma in situ or node-negative breast cancer treated by breast conserving surgery were randomly assigned (1:1) to receive either external beam APBI (38·5 Gy in ten fractions delivered twice per day over 5–8 days) or whole breast irradiation (42·5 Gy in 16 fractions once per day over 21 days, or 50 Gy in 25 fractions once per day over 35 days). Patients and clinicans were not masked to treatment assignment. The primary outcome was ipsilateral breast tumour recurrence (IBTR), analysed by intention to treat. The trial was designed on the basis of an expected 5 year IBTR rate of 1·5% in the whole breast irradiation group with 85% power to exclude a 1·5% increase in the APBI group; non-inferiority was shown if the upper limit of the two-sided 90% CI for the IBTR hazard ratio (HR) was less than 2·02. This trial is registered with ClinicalTrials.gov , NCT00282035 . Findings Between Feb 7, 2006, and July 15, 2011, we enrolled 2135 women. 1070 were randomly assigned to receive APBI and 1065 were assigned to receive whole breast irradiation. Six patients in the APBI group withdrew before treatment, four more did not receive radiotherapy, and 16 patients received whole breast irradiation. In the whole breast irradiation group, 16 patients withdrew, and two more did not receive radiotherapy. In the APBI group, a further 14 patients were lost to follow-up and nine patients withdrew during the follow-up period. In the whole breast irradiation group, 20 patients were lost to follow-up and 35 withdrew during follow-up. Median follow-up was 8·6 years (IQR 7·3–9·9). The 8-year cumulative rates of IBTR were 3·0% (95% CI 1·9–4·0) in the APBI group and 2·8% (1·8–3·9) in the whole breast irradiation group. The HR for APBI versus whole breast radiation was 1·27 (90% CI 0·84–1·91). Acute radiation toxicity (grade ≥2, within 3 months of radiotherapy start) occurred less frequently in patients treated with APBI (300 [28%] of 1070 patients) than whole breast irradiation (484 [45%] of 1065 patients, p Interpretation External beam APBI was non-inferior to whole breast irradiation in preventing IBTR. Although less acute toxicity was observed, the regimen used was associated with an increase in moderate late toxicity and adverse cosmesis, which might be related to the twice per day treatment. Other approaches, such as treatment once per day, might not adversely affect cosmesis and should be studied. Funding Canadian Institutes for Health Research and Canadian Breast Cancer Research Alliance.

BACKGROUNDCytomegalovirus (CMV) is the most common intrauterine infection, leading to infant brain damage. Prognostic assessment of CMV-infected fetuses has remained an ongoing challenge in prenatal care, in the absence of established prenatal biomarkers of congenital CMV (cCMV) infection severity. We aimed to identify prognostic biomarkers of cCMV-related fetal brain injury.METHODSWe performed global proteome analysis of mid-gestation amniotic fluid samples, comparing amniotic fluid of fetuses with severe cCMV with that of asymptomatic CMV-infected fetuses. The levels of selected differentially excreted proteins were further determined by specific immunoassays.RESULTSUsing unbiased proteome analysis in a discovery cohort, we identified amniotic fluid proteins related to inflammation and neurological disease pathways, which demonstrated distinct abundance in fetuses with severe cCMV. Amniotic fluid levels of 2 of these proteins - the immunomodulatory proteins retinoic acid receptor responder 2 (chemerin) and galectin-3-binding protein (Gal-3BP) - were highly predictive of the severity of cCMV in an independent validation cohort, differentiating between fetuses with severe (n = 17) and asymptomatic (n = 26) cCMV, with 100%-93.8% positive predictive value, and 92.9%-92.6% negative predictive value (for chemerin and Gal-3BP, respectively). CONCLUSIONAnalysis of chemerin and Gal-3BP levels in mid-gestation amniotic fluids could be used in the clinical setting to profoundly improve the prognostic assessment of CMV-infected fetuses.FUNDINGIsrael Science Foundation (530/18 and IPMP 3432/19); Research Fund - Hadassah Medical Organization.

Cyanobacteria have massively contributed to carbonate deposit formation over the geological history. They are traditionally thought to biomineralize CaCO3 extracellularly as an indirect byproduct of photosynthesis. However, the recent discovery of freshwater cyanobacteria forming intracellular amorphous calcium carbonates (iACC) challenges this view. Despite the geochemical interest of such a biomineralization process, its molecular mechanisms and evolutionary history remain elusive. Here, using comparative genomics, we identify a new gene (ccyA) and protein (calcyanin) family specifically associated with cyanobacterial iACC biomineralization. Calcyanin is composed of a conserved C-terminal domain, which likely adopts an original fold, and a variable N-terminal domain whose structure allows differentiating 4 major types among the 35 known calcyanin homologues. Calcyanin lacks detectable full-length homologs with known function. Yet, genetic and comparative genomic analyses suggest a possible involvement in Ca homeostasis, making this gene family a particularly interesting target for future functional studies. Whatever its function, this new gene family appears as a gene diagnostic of intracellular calcification in cyanobacteria. By searching for ccyA in publicly available genomes, we identified 13 additional cyanobacterial strains forming iACC. This significantly extends our knowledge about the phylogenetic and environmental distribution of cyanobacterial iACC biomineralization, especially with the detection of multicellular genera as well as a marine species. Phylogenetic analyses indicate that iACC biomineralization is ancient, with independent losses in various lineages and some HGT cases that resulted in the broad but patchy distribution of calcyanin across modern cyanobacteria. Overall, iACC biomineralization emerges as a new case of genetically controlled biomineralization in bacteria.Significance statementFew freshwater species of Cyanobacteria have been known to mineralize amorphous CaCO3 (ACC) intracellularly. Despite the geochemical interest of this biomineralization, its evolutionary history and molecular mechanism remain poorly known. Here, we report the discovery of a new gene family that has no homolog with known function, which proves to be a good diagnostic marker of this process. It allowed to find cyanobacteria in several phyla and environments such as seawater, where ACC biomineralization had not been reported before. Moreover, this gene is ancient and was independently lost in various lineages with some later horizontal transfers, resulting in a broad and patchy phylogenetic distribution in modern cyanobacteria.

Along-strike variation in the geometry of lithospheric structures is a key control parameter for the occurrence and propagation of major interplate earthquakes in subduction and collision zones. The lateral segmentation of the Himalayan arc is now well-established from various observations, including topography, gravity anomalies, exhumation rates, and present-day seismic activity. Good knowledge of the main geometric features of these segments and their boundaries is thus the next step to improve seismic hazard assessment in this area. Following recent studies, we focus our approach on the transition zone between Nepal and Bhutan where both M > 8 earthquakes and changes in the geometry of the Indian plate have been documented. Ground gravity data sets are combined with satellite gravity gradients provided by the GOCE mission (Gravity Field and Steady-State Ocean Circulation Explorer) in a joint inversion to assess the location and the geometry of this transition. We obtain a ca. 10 km wide transition zone located at the western border of Bhutan that is aligned with the Madhupur fault in the foreland and coincides with the Dhubri–Chungthang fault zone and the Yadong-Gulu rift in Himalaya and southern Tibet, respectively. This sharp segment boundary at depth can act as a barrier to earthquake rupture propagation. It can possibly restrict the size of large earthquakes and thus reduce the occurrence probability of M > 9 earthquakes along the Main Himalayan Thrust.