protocol of a randomized trial

H4A Primary Healthcare Research Network scholars programme for support of research in the protocol design phase. This article will also be supported by National Funds through FCT - Fundação para a Ciência e a Tecnologia,I.P., within CINTESIS, R&D Unit (reference UIDB/4255/2020).BACKGROUND: Screening with prostate-specific antigen (PSA) test for prostate cancer is considered a preference sensitive decision; meaning it does not only depend on what is best from a medical point of view, but also from a patient value standpoint. Decision aids are evidence-based tools which are shown to help people feel clearer about their values; therefore it has been advocated that decision aids should contain a specific values clarification method (VCM). VCMs may be either implicit or explicit, but the evidence concerning the best method is scarce. We aim to compare the perceived clarity of personal values in men considering PSA screening using decision aids with no VCM versus an implicit VCM versus an explicit VCM. METHODS: Male factory employees from an industrial facility in the Northern region of Portugal aged 50 to 69 years old will be randomly assigned to one of three decision aid groups used to support prostate cancer screening decisions: (i) decision aid with information only (control), (ii) decision aid with information plus an implicit VCM, (iii) decision aid with information plus an explicit VCM. Men will be allowed release time from work to attend a session at their workplace. After a brief oral presentation, those willing to participate in the study will fill the baseline questionnaire, plus a 5 point-Likert scale question about intentions to undergo screening, and will then receive the intervention materials to complete. We estimated a total sample size of 276 participants; with 92 in each group. The primary outcome will be the perceived clarity of personal values assessed by the Portuguese validated translation of the three subscales of the Decisional Conflict Scale. Secondary outcomes will be intention to be screened (before and after the intervention), the total score from the Decisional Conflict Scale and the self-report of having or not undergone screening at 6 months. DISCUSSION: This study will add to the body of evidence on the role of decision aids to support health preference-sensitive choices and provide further insight on the impact of different methods for eliciting people's values embedded within a decision aid. TRIAL REGISTRATION: NCT03988673 - clinicalTrials.gov (2019/06/17).publishersversionpublishe

Derivation and Characterization of Induced Pluripotent Stem Cells from Equine Fibroblasts

Pluripotent stem cells offer unprecedented potential not only for human medicine but also for veterinary medicine, particularly in relation to the horse. Induced pluripotent stem cells (iPSCs) are particularly promising, as they are functionally similar to embryonic stem cells and can be generated in vitro in a patient-specific manner. In this study, we report the generation of equine iPSCs from skin fibroblasts obtained from a foal and reprogrammed using viral vectors coding for murine Oct4, Sox2, c-Myc, and Klf4 sequences. The reprogrammed cell lines were morphologically similar to iPSCs reported from other species and could be stably maintained over more than 30 passages. Immunostaining and polymerase chain reaction analyses revealed that these cell lines expressed an array of endogenous markers associated with pluripotency, including OCT4, SOX2, NANOG, REX1, LIN28, SSEA1, SSEA4, and TRA1-60. Furthermore, under the appropriate conditions, the equine iPSCs readily formed embryoid bodies and differentiated in vitro into cells expressing markers of ectoderm, mesoderm, and endoderm, and when injected into immunodeficient mice, gave raise to tumors containing differentiated derivatives of the 3 germ layers. Finally, we also reprogrammed fibroblasts from a 2-year-old horse. The reprogrammed cells were similar to iPSCs derived from neonatal fibroblasts in terms of morphology, expression of pluripotency markers, and differentiation ability. The generation of these novel cell lines constitutes an important step toward the understanding of pluripotency in the horse, and paves the way for iPSC technology to potentially become a powerful research and clinical tool in veterinary biomedicine

Mapping social reward and punishment processing in the human brain:A voxel-based meta-analysis of neuroimaging findings using the social incentive delay task

Social rewards or punishments motivate human learning and behaviour, and alterations in the brain circuits involved in the processing of these stimuli have been linked with several neuropsychiatric disorders. However, questions still remain about the exact neural substrates implicated in social reward and punishment processing. Here, we conducted four Anisotropic Effect Size Signed Differential Mapping voxel-based meta-analyses of fMRI studies investigating the neural correlates of the anticipation and receipt of social rewards and punishments using the Social Incentive Delay task. We found that the anticipation of both social rewards and social punishment avoidance recruits a wide network of areas including the basal ganglia, the midbrain, the dorsal anterior cingulate cortex, the supplementary motor area, the anterior insula, the occipital gyrus and other frontal, temporal, parietal and cerebellar regions not captured in previous coordinate-based meta-analysis. We identified decreases in the BOLD signal during the anticipation of both social reward and punishment avoidance in regions of the default-mode network that were missed in individual studies likely due to a lack of power. Receipt of social rewards engaged a robust network of brain regions including the ventromedial frontal and orbitofrontal cortices, the anterior cingulate cortex, the amygdala, the hippocampus, the occipital cortex and the brainstem, but not the basal ganglia. Receipt of social punishments increased the BOLD signal in the orbitofrontal cortex, superior and inferior frontal gyri, lateral occipital cortex and the insula. In contrast to the receipt of social rewards, we also observed a decrease in the BOLD signal in the basal ganglia in response to the receipt of social punishments. Our results provide a better understanding of the brain circuitry involved in the processing of social rewards and punishment. Furthermore, they can inform hypotheses regarding brain areas where disruption in activity may be associated with dysfunctional social incentive processing during diseas

Hidden Quantum Gravity in 3d Feynman diagrams

In this work we show that 3d Feynman amplitudes of standard QFT in flat and homogeneous space can be naturally expressed as expectation values of a specific topological spin foam model. The main interest of the paper is to set up a framework which gives a background independent perspective on usual field theories and can also be applied in higher dimensions. We also show that this Feynman graph spin foam model, which encodes the geometry of flat space-time, can be purely expressed in terms of algebraic data associated with the Poincare group. This spin foam model turns out to be the spin foam quantization of a BF theory based on the Poincare group, and as such is related to a quantization of 3d gravity in the limit where the Newton constant G_N goes to 0. We investigate the 4d case in a companion paper where the strategy proposed here leads to similar results.Comment: 35 pages, 4 figures, some comments adde

Imaging Coulomb Islands in a Quantum Hall Interferometer

In the Quantum Hall regime, near integer filling factors, electrons should only be transmitted through spatially-separated edge states. However, in mesoscopic systems, electronic transmission turns out to be more complex, giving rise to a large spectrum of magnetoresistance oscillations. To explain these observations, recent models put forward that, as edge states come close to each other, electrons can hop between counterpropagating edge channels, or tunnel through Coulomb islands. Here, we use scanning gate microscopy to demonstrate the presence of quantum Hall Coulomb islands, and reveal the spatial structure of transport inside a quantum Hall interferometer. Electron islands locations are found by modulating the tunneling between edge states and confined electron orbits. Tuning the magnetic field, we unveil a continuous evolution of active electron islands. This allows to decrypt the complexity of high magnetic field magnetoresistance oscillations, and opens the way to further local scale manipulations of quantum Hall localized states

The VLT-FLAMES Tarantula Survey III: A very massive star in apparent isolation from the massive cluster R136

VFTS 682 is located in an active star-forming region, at a projected distance of 29 pc from the young massive cluster R136 in the Tarantula Nebula of the Large Magellanic Cloud. It was previously reported as a candidate young stellar object, and more recently spectroscopically revealed as a hydrogen-rich Wolf-Rayet (WN5h) star. Our aim is to obtain the stellar properties, such as its intrinsic luminosity, and to investigate the origin of VFTS 682. To this purpose, we model optical spectra from the VLT-FLAMES Tarantula Survey with the non-LTE stellar atmosphere code CMFGEN, as well as the spectral energy distribution from complementary optical and infrared photometry. We find the extinction properties to be highly peculiar (RV ~4.7), and obtain a surprisingly high luminosity log(L/Lsun) = 6.5 \pm 0.2, corresponding to a present-day mass of ~150Msun. The high effective temperature of 52.2 \pm 2.5kK might be explained by chemically homogeneous evolution - suggested to be the key process in the path towards long gamma-ray bursts. Lightcurves of the object show variability at the 10% level on a timescale of years. Such changes are unprecedented for classical Wolf-Rayet stars, and are more reminiscent of Luminous Blue Variables. Finally, we discuss two possibilities for the origin of VFTS 682: (i) the star either formed in situ, which would have profound implications for the formation mechanism of massive stars, or (ii) VFTS 682 is a slow runaway star that originated from the dense cluster R136, which would make it the most massive runaway known to date.Comment: 5 pages, 5 figures, accepted by A&A Letter

The VLT-FLAMES Tarantula survey XX. The nature of the X-ray bright emission-line star VFTS 399

Context. The stellar population of the 30 Doradus star-forming region in the Large Magellanic Cloud contains a subset of apparently single, rapidly rotating O-type stars. The physical processes leading to the formation of this cohort are currently uncertain. Aims. One member of this group, the late O-type star VFTS 399, is found to be unexpectedly X-ray bright for its bolometric luminosity − in this study we aim to determine its physical nature and the cause of this behaviour. Methods. To accomplish this we performed a time-resolved analysis of optical, infrared and X-ray observations. Results. We found VFTS 399 to be an aperiodic photometric variable with an apparent near-IR excess. Its optical spectrum demonstrates complex emission profiles in the lower Balmer series and select He i lines − taken together these suggest an OeBe classification. The highly variable X-ray luminosity is too great to be produced by a single star, while the hard, non-thermal nature suggests the presence of an accreting relativistic companion. Finally, the detection of periodic modulation of the X-ray lightcurve is most naturally explained under the assumption that the accretor is a neutron star. Conclusions. VFTS 399 appears to be the first high-mass X-ray binary identified within 30 Dor, sharing many observational characteristics with classical Be X-ray binaries. Comparison of the current properties of VFTS 399 to binary-evolution models suggests a progenitor mass ≳25 M⊙ for the putative neutron star, which may host a magnetic field comparable in strength to those of magnetars. VFTS 399 is now the second member of the cohort of rapidly rotating “single” O-type stars in 30 Dor to show evidence of binary interaction resulting in spin-up, suggesting that this may be a viable evolutionary pathway for the formation of a subset of this stellar population

Global trends in aquatic animal tracking with acoustic telemetry

Acoustic telemetry (AT) is a rapidly evolving technique used to track the movements of aquatic animals. As the capacity of AT research expands it is important to optimize its relevance to management while still pursuing key ecological questions. A global review of AT literature revealed region-specific research priorities underscoring the breadth of how AT is applied, but collectively demonstrated a lack of management-driven objectives, particularly relating to fisheries, climate change, and protection of species. In addition to the need for more research with direct pertinence to management, AT research should prioritize ongoing efforts to create collaborative opportunities, establish long-term and ecosystem-based monitoring, and utilize technological advancements to bolster aquatic policy and ecological understanding worldwide

The role of multiple marks in epigenetic silencing and the emergence of a stable bivalent chromatin state

We introduce and analyze a minimal model of epigenetic silencing in budding yeast, built upon known biomolecular interactions in the system. Doing so, we identify the epigenetic marks essential for the bistability of epigenetic states. The model explicitly incorporates two key chromatin marks, namely H4K16 acetylation and H3K79 methylation, and explores whether the presence of multiple marks lead to a qualitatively different systems behavior. We find that having both modifications is important for the robustness of epigenetic silencing. Besides the silenced and transcriptionally active fate of chromatin, our model leads to a novel state with bivalent (i.e., both active and silencing) marks under certain perturbations (knock-out mutations, inhibition or enhancement of enzymatic activity). The bivalent state appears under several perturbations and is shown to result in patchy silencing. We also show that the titration effect, owing to a limited supply of silencing proteins, can result in counter-intuitive responses. The design principles of the silencing system is systematically investigated and disparate experimental observations are assessed within a single theoretical framework. Specifically, we discuss the behavior of Sir protein recruitment, spreading and stability of silenced regions in commonly-studied mutants (e.g., sas2, dot1) illuminating the controversial role of Dot1 in the systems biology of yeast silencing.Comment: Supplementary Material, 14 page

Macro-Climatic Distribution Limits Show Both Niche Expansion and Niche Specialization among C4 Panicoids

Grasses are ancestrally tropical understory species whose current dominance in warm open habitats is linked to the evolution of C4 photosynthesis. C4 grasses maintain high rates of photosynthesis in warm and water stressed environments, and the syndrome is considered to induce niche shifts into these habitats while adaptation to cold ones may be compromised. Global biogeographic analyses of C4 grasses have, however, concentrated on diversity patterns, while paying little attention to distributional limits. Using phylogenetic contrast analyses, we compared macro-climatic distribution limits among ~1300 grasses from the subfamily Panicoideae, which includes 4/5 of the known photosynthetic transitions in grasses. We explored whether evolution of C4 photosynthesis correlates with niche expansions, niche changes, or stasis at subfamily level and within the two tribes Paniceae and Paspaleae. We compared the climatic extremes of growing season temperatures, aridity, and mean temperatures of the coldest months. We found support for all the known biogeographic distribution patterns of C4 species, these patterns were, however, formed both by niche expansion and niche changes. The only ubiquitous response to a change in the photosynthetic pathway within Panicoideae was a niche expansion of the C4 species into regions with higher growing season temperatures, but without a withdrawal from the inherited climate niche. Other patterns varied among the tribes, as macro-climatic niche evolution in the American tribe Paspaleae differed from the pattern supported in the globally distributed tribe Paniceae and at family level.Fil: Aagesen, Lone. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Botánica Darwinion. Academia Nacional de Ciencias Exactas, Físicas y Naturales. Instituto de Botánica Darwinion; ArgentinaFil: Biganzoli, Fernando. Universidad de Buenos Aires. Facultad de Agronomía. Departamento de Métodos Cuantitativos y Sistemas de Información; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bena, María Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Botánica Darwinion. Academia Nacional de Ciencias Exactas, Físicas y Naturales. Instituto de Botánica Darwinion; ArgentinaFil: Godoy Bürki, Ana Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Botánica Darwinion. Academia Nacional de Ciencias Exactas, Físicas y Naturales. Instituto de Botánica Darwinion; ArgentinaFil: Reinheimer, Renata. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Agrobiotecnología del Litoral. Universidad Nacional del Litoral. Instituto de Agrobiotecnología del Litoral; ArgentinaFil: Zuloaga, Fernando Omar. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Botánica Darwinion. Academia Nacional de Ciencias Exactas, Físicas y Naturales. Instituto de Botánica Darwinion; Argentin