The Collaborative Islet Transplant Registry (CITR) collects data on clinical islet isolations and transplants. This retrospective report analyzed 1017 islet isolation procedures performed for 537 ...recipients of allogeneic clinical islet transplantation in 1999–2010. This study describes changes in donor and islet isolation variables by era and factors associated with quantity and quality of final islet products. Donor body weight and BMI increased significantly over the period (p < 0.001). Islet yield measures have improved with time including islet equivalent (IEQ)/particle ratio and IEQs infused. The average dose of islets infused significantly increased in the era of 2007–2010 when compared to 1999–2002 (445.4 ± 156.8 vs. 421.3 ± 155.4 ×103 IEQ; p < 0.05). Islet purity and total number of β cells significantly improved over the study period (p < 0.01 and <0.05, respectively). Otherwise, the quality of clinical islets has remained consistently very high through this period, and differs substantially from nonclinical islets. In multivariate analysis of all recipient, donor and islet factors, and medical management factors, the only islet product characteristic that correlated with clinical outcomes was total IEQs infused. This analysis shows improvements in both quantity and some quality criteria of clinical islets produced over 1999–2010, and these parallel improvements in clinical outcomes over the same period.
Product criteria from clinical grade allogeneic human islets exhibit consistently superior‐quality characteristics and significantly increasing islet equivalent yield, paralleling improving success rates of islet transplantation for type I diabetes.
Recent tests of a single module of the Jagiellonian Positron Emission Tomography system (J-PET) consisting of 30 cm long plastic scintillator strips have proven its applicability for the detection of ...annihilation quanta (0.511 MeV) with a coincidence resolving time (CRT) of 0.266 ns. The achieved resolution is almost by a factor of two better with respect to the current TOF-PET detectors and it can still be improved since, as it is shown in this article, the intrinsic limit of time resolution for the determination of time of the interaction of 0.511 MeV gamma quanta in plastic scintillators is much lower. As the major point of the article, a method allowing to record timestamps of several photons, at two ends of the scintillator strip, by means of matrix of silicon photomultipliers (SiPM) is introduced. As a result of simulations, conducted with the number of SiPM varying from 4 to 42, it is shown that the improvement of timing resolution saturates with the growing number of photomultipliers, and that the Formula: see text configuration at two ends allowing to read twenty timestamps, constitutes an optimal solution. The conducted simulations accounted for the emission time distribution, photon transport and absorption inside the scintillator, as well as quantum efficiency and transit time spread of photosensors, and were checked based on the experimental results. Application of the Formula: see text matrix of SiPM allows for achieving the coincidence resolving time in positron emission tomography of Formula: see text0.170 ns for 15 cm axial field-of-view (AFOV) and Formula: see text0.365 ns for 100 cm AFOV. The results open perspectives for construction of a cost-effective TOF-PET scanner with significantly better TOF resolution and larger AFOV with respect to the current TOF-PET modalities.
Egg‐yolk antibodies (IgY) against somatostatin‐14 (anti‐SST‐14) were evaluated as orally administered, growth promotants in gastric rainbow trout (Oncorhynchus mykiss) and agastric common carp ...(Cyprinus carpio) in an 8‐week feeding trial. Feeding groups were compared with fish which did not receive anti‐SST‐14 IgY. Growth responses and IgY plasma contents of the blood were assessed. In contrast to rainbow trout, oral anti‐SST‐14 addition to carp significantly improved protein efficiency ratio (PER, 1.02 ± 0.04) and protein productive value (PPV, 26.7 ± 0.91) after 56 days (P < 0.05) compared to the negative control (PER = 0.91 ± 0.02; PPV = 22.9 ± 0.66). IgY was undetectable in plasma of rainbow trout after oral administration, indicating that gastric degradation of the fed IgY makes this application route for growth promotion in gastric trout challenging.
INTRODUCTIONInfections are responsible for a part of the overall mortality in primary Sjögren's syndrome patients (pSS). Our retrospective monocentric study aimed at describing infections reported in ...a population of pSS hospitalized patients, along with the characteristics of their disease. METHODSPatients with SS have been randomly selected from our hospital database claim, between 2009 and 2018. After careful analysis of their medical chart, only patients with pSS and fulfilling ACR/EULAR 2016 diagnosis criteria were included. We collected main clinical, biological and pathological characteristics of SS, along with all the reported infections during the follow-up. The characteristics of the disease were compared according to the presence of an infection in hospitalization. RESULTSIn total, 109 pSS patients were included (93% of women, mean age 53.6±14.3 years, mean follow-up 8.2±8.4 years). Fifty-one percent had been exposed to hydroxychloroquine (HCQ). Seventy-eight infections were recorded in 47 (43%) patients. Twenty-five infections were recorded in hospitalization (5 in critical care) in 20 (18%) patients, whom leading causes were urinary tract (28%), pulmonary (24%), ENT (16%), and intestinal (12%) infections. pSS patients with infections in hospitalization were older, exhibited more hypocomplementemia, and were less exposed to HCQ. We found no difference in immunosuppressive treatments exposure. CONCLUSIONSThe impact of HCQ exposure on infectious risk needs further investigations. Broad vaccination campaign and tight control of sicca syndrome could lead to a better control of infection risk.
Many objects in the real world have features that vary over time, creating uncertainty in how they will look in the future. This uncertainty makes statistical knowledge about the likelihood of ...features critical to attention demanding processes such as visual search. However, little is known about how the uncertainty of visual features is integrated into predictions about search targets in the brain. In the current study, we test the idea that regions prefrontal cortex code statistical knowledge about search targets before the onset of search. Across 20 human participants (13 female; 7 male), we observe target identity in the multivariate pattern and uncertainty in the overall activation of dorsolateral prefrontal cortex (DLPFC) and inferior frontal junction (IFJ) in advance of the search display. This indicates that the target identity (mean) and uncertainty (variance) of the target distribution are coded independently within the same regions. Furthermore, once the search display appears the univariate IFJ signal scaled with the distance of the actual target from the expected mean, but more so when expected variability was low. These results inform neural theories of attention by showing how the prefrontal cortex represents both the identity and expected variability of features in service of top-down attentional control.
Theories of attention and working memory posit that when we engage in complex cognitive tasks our performance is determined by how precisely we remember task-relevant information. However, in the real world the properties of objects change over time, creating uncertainty about many aspects of the task. There is currently a gap in our understanding of how neural systems represent this uncertainty and combine it with target identity information in anticipation of attention demanding cognitive tasks. In this study, we show that the prefrontal cortex represents identity and uncertainty as unique codes before task onset. These results advance theories of attention by showing that the prefrontal cortex codes both target identity and uncertainty to implement top-down attentional control.
Visual attention is often characterized as being guided by precise memories for target objects. However, real-world search targets have dynamic features that vary over time, meaning that observers ...must predict how the target could look based on how features are expected to change. Despite its importance, little is known about how target feature predictions influence feature-based attention, or how these predictions are represented in the target template. In Experiment 1 (N = 60 university students), we show observers readily track the statistics of target features over time and adapt attentional priority to predictions about the distribution of target features. In Experiments 2a and 2b (N = 480 university students), we show that these predictions are encoded into the target template as a distribution of likelihoods over possible target features, which are independent of memory precision for the cued item. These results provide a novel demonstration of how observers represent predicted feature distributions when target features are uncertain and show that these predictions are used to set attentional priority during visual search.
Public Significance Statement
Theories of attention and working memory posit that when we engage in complex cognitive tasks, our performance is determined by how precisely we remember task-relevant information. However, in the real world, properties of objects change over time, creating uncertainty about many aspects of the task. There is currently a gap in our understanding of how cognitive systems overcome this uncertainty when engaging in common behaviors like visual search. In two studies we show that when searching for target objects, observers readily learn the distribution of possible target features and leverage this information to make predictions about which features will best guide attention in the upcoming search. Further, we show that these predictions are distinct from memory, and uniquely influence attention when search targets are uncertain. These results help advance theories of attention and working memory by explaining how we use learning and prediction to overcome uncertainty in the environment.
In the adult, new blood vessel formation can occur either through angiogenesis from pre-existing mature endothelium or vasculogenesis mediated by bone marrow-derived endothelial precursors. We ...recently isolated endothelial progenitor cells, or angioblasts, in human adult bone marrow which have selective migratory properties for ischemic tissues, including myocardium, to where they home and induce vasculogenesis. Here we show that myocardial production of the IL-8/Gro-alpha CXC chemokine family is significantly increased after acute ischemia, and that this provides a chemoattractant gradient for bone marrow-derived endothelial progenitors, or angioblasts. This chemokine-mediated homing of bone marrow angioblasts to the ischemic heart regulates their ability to induce myocardial neovascularization, protection against cardiomyocyte apoptosis, and functional cardiac recovery. Together, our results indicate that CXC chemokines play a central role in regulating vasculogenesis in the adult, and suggest that manipulation of interactions between chemokines and their receptors on autologous human bone marrow-derived angioblasts could augment neovascularization of ischemic myocardial tissue.
Animals abstract compact representations of a task’s structure, which supports accelerated learning and flexible behavior. Whether and how such abstracted representations may be used to assign credit ...for inferred, but unobserved, relationships in structured environments are unknown. We develop a hierarchical reversal-learning task and Bayesian learning model to assess the computational and neural mechanisms underlying how humans infer specific choice-outcome associations via structured knowledge. We find that the medial prefrontal cortex (mPFC) efficiently represents hierarchically related choice-outcome associations governed by the same latent cause, using a generalized code to assign credit for both experienced and inferred outcomes. Furthermore, the mPFC and lateral orbitofrontal cortex track the current “position” within a latent association space that generalizes over stimuli. Collectively, these findings demonstrate the importance of both tracking the current position in an abstracted task space and efficient, generalizable representations in the prefrontal cortex for supporting flexible learning and inference in structured environments.
•Dopaminergic midbrain and frontal areas update experienced and inferred associations•mPFC uses a generalized code for observed and inferred credit assignment•mPFC tracks the evolving estimated “position” in the association space
Witkowski et al. show that prefrontal cortical areas both track the inferred “position” in a task space defined by hierarchically related associations governed by a common latent cause and reinstate these latent causes at feedback to assign credit to the inferred associations.
We consider a holographic model of two 1+1-dimensional heat baths at different temperatures joined at time t = 0, such that a steady state heat-current region forms and expands in space for times t > ...0. After commenting on the causal structure of the dual 2+1-dimensional spacetime, we present how to calculate the time-dependent entanglement entropy of the boundary system holographically. We observe that the increase rate of the entanglement entropy satisfies certain bounds known from the literature on entanglement tsunamis. Furthermore, we check the validity of several non-trivial entanglement inequalities in this dynamic system.
The orbital frontal cortex (OFC) has long been linked to goal-directed, flexible behaviors. Recent evidence suggests the OFC plays key roles in representing the abstracted structure of task spaces, ...and using this representation for flexible inferences during both learning and choice. Here, we review convergent evidence from studies in animal models and humans in support of this view. We begin by considering early accounts of OFC function, then discuss how more recent evidence supports theories that have re-cast OFC's function as representing the structure of a task or environment for flexible inference. Finally, we turn to neural recording studies that provide insights into the underlying representations and computations the OFC may implement in coordination with other brain areas.
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