Characterizing object- and position-dependent response profiles to uni- and bilateral stimulus configurations in human higher visual cortex:a 7T fMRI study

Visual scenes are initially processed via segregated neural pathways dedicated to either of the two visual hemifields. Although higher-order visual areas are generally believed to utilize invariant object representations (abstracted away from features such as stimulus position), recent findings suggest they retain more spatial information than previously thought. Here, we assessed the nature of such higher-order object representations in human cortex using high-resolution fMRI at 7T, supported by corroborative 3T data. We show that multi-voxel activation patterns in both the contra- and ipsilateral hemisphere can be exploited to successfully classify the object category of unilaterally presented stimuli. Moreover, robustly identified rank order-based response profiles demonstrated a strong contralateral bias which frequently outweighed object category preferences. Finally, we contrasted different combinatorial operations to predict the responses during bilateral stimulation conditions based on responses to their constituent unilateral elements. Results favored a max operation predominantly reflecting the contralateral stimuli. The current findings extend previous work by showing that configuration-dependent modulations in higher-order visual cortex responses as observed in single unit activity have a counterpart in human neural population coding. They furthermore corroborate the emerging view that position coding is a fundamental functional characteristic of ventral visual stream processing

Creating and Certifying the Professional Mediator -- Education and Credentialing

Existing and pending law school mediation programs, post-graduate mediator training programs, mentorship programs, credentialing movements, and continuing mediation education were examined by a panel and speakers directly involved in those fields. Are we effectively training new mediators in law schools and post-graduate programs? Should we, and how can we, credential mediators? Do good mediators need to be re-trained? How would continuing mediation educational requirements be implemented

Creating and Certifying the Professional Mediator -- Education and Credentialing

Existing and pending law school mediation programs, post-graduate mediator training programs, mentorship programs, credentialing movements, and continuing mediation education were examined by a panel and speakers directly involved in those fields. Are we effectively training new mediators in law schools and post-graduate programs? Should we, and how can we, credential mediators? Do good mediators need to be re-trained? How would continuing mediation educational requirements be implemented

Theta-phase dependent neuronal coding during sequence learning in human single neurons

This work was supported by grants from the French Agence Nationale de la Recherche (ANR-12-JSH2-0004-01 and ANR AI-REPS–18-CE37-0007-01), the Fyssen foundation, and the Université Paul Sabatier, Toulouse, France (BQR, 2009 and Appel à Projets de Recherche Labellisés, 2013), to L.R., the European Research Council (ERC Consolidator Grant P-Cycles number 614244), the French Agence Nationale de la Recherche (ANR OSCI-DEEP ANR-19-NEUC-0004), and an ANITI (Artificial and Natural Intelligence Toulouse Institute) Research Chair (ANR-19-PI3A-0004) to R.V., the Studienstiftung des Deutschen Volkes (German Academic Scholarship Foundation) to B.Z., the European Union (ERC Grant Agreement n. 339490 “Cortic_al_gorithms” and grant agreements 720270 and 785907 “Human Brain Project SGA1 and SGA2’) and the Friends Foundation of the Netherlands Institute for Neuroscience to P.R.R.The ability to maintain a sequence of items in memory is a fundamental cognitive function. In the rodent hippocampus, the representation of sequentially organized spatial locations is reflected by the phase of action potentials relative to the theta oscillation (phase precession). We investigated whether the timing of neuronal activity relative to the theta brain oscillation also reflects sequence order in the medial temporal lobe of humans. We used a task in which human participants learned a fixed sequence of pictures and recorded single neuron and local field potential activity with implanted electrodes. We report that spikes for three consecutive items in the sequence (the preferred stimulus for each cell, as well as the stimuli immediately preceding and following it) were phase-locked at distinct phases of the theta oscillation. Consistent with phase precession, spikes were fired at progressively earlier phases as the sequence advanced. These findings generalize previous findings in the rodent hippocampus to the human temporal lobe and suggest that encoding stimulus information at distinct oscillatory phases may play a role in maintaining sequential order in memory.Publisher PDFPeer reviewe

The Cardiac Care Bridge transitional care program for the management of older high-risk cardiac patients: An economic evaluation alongside a randomized controlled trial

Objective To evaluate the cost-effectiveness of the Cardiac Care Bridge (CCB) nurse-led transitional care program in older (≥70 years) cardiac patients compared to usual care. Methods The intervention group (n = 153) received the CCB program consisting of case management, disease management and home-based cardiac rehabilitation in the transition from hospital to home on top of usual care and was compared with the usual care group (n = 153). Outcomes included a composite measure of first all-cause unplanned hospital readmission or mortality, Quality Adjusted Life Years (QALYs) and societal costs within six months follow-up. Missing data were imputed using multiple imputation. Statistical uncertainty surrounding Incremental Cost-Effectiveness Ratios (ICERs) was estimated by using bootstrapped seemingly unrelated regression. Results No significant between group differences in the composite outcome of readmission or mortality nor in societal costs were observed. QALYs were statistically significantly lower in the intervention group, mean difference -0.03 (95% CI: -0.07; -0.02). Cost-effectiveness acceptability curves showed that the maximum probability of the intervention being cost-effective was 0.31 at a Willingness To Pay (WTP) of €0,00 and 0.14 at a WTP of €50,000 per composite outcome prevented and 0.32 and 0.21, respectively per QALY gained. Conclusion The CCB program was on average more expensive and less effective compared to usual care, indicating that the CCB program is dominated by usual care. Therefore, the CCB program cannot be considered cost-effective compared to usual care

Aseptic Meningitis Epidemic during a West Nile Virus Avian Epizootic

While enteroviruses have been the most commonly identified cause of aseptic meningitis in the United States, the role of the emerging, neurotropic West Nile virus (WNV) is not clear. In summer 2001, an aseptic meningitis epidemic occurring in an area of a WNV epizootic in Baltimore, Maryland, was investigated to determine the relative contributions of WNV and enteroviruses. A total of 113 aseptic meningitis cases with onsets from June 1 to September 30, 2001, were identified at six hospitals. WNV immunoglobulin M tests were negative for 69 patients with available specimens; however, 43 (61%) of 70 patients tested enterovirus-positive by viral culture or polymerase chain reaction. Most (76%) of the serotyped enteroviruses were echoviruses 13 and 18. Enteroviruses, including previously rarely detected echoviruses, likely caused most aseptic meningitis cases in this epidemic. No WNV meningitis cases were identified. Even in areas of WNV epizootics, enteroviruses continue to be important causative agents of aseptic meningitis

New ophthalmosaurid ichthyosaurs from the European lower cretaceous demonstrate extensive ichthyosaur survival across the Jurassic–Cretaceous boundary

Background Ichthyosauria is a diverse clade of marine amniotes that spanned most of the Mesozoic. Until recently, most authors interpreted the fossil record as showing that three major extinction events affected this group during its history: one during the latest Triassic, one at the Jurassic–Cretaceous boundary (JCB), and one (resulting in total extinction) at the Cenomanian-Turonian boundary. The JCB was believed to eradicate most of the peculiar morphotypes found in the Late Jurassic, in favor of apparently less specialized forms in the Cretaceous. However, the record of ichthyosaurs from the Berriasian–Barremian interval is extremely limited, and the effects of the end-Jurassic extinction event on ichthyosaurs remains poorly understood. Methodology/Principal Findings Based on new material from the Hauterivian of England and Germany and on abundant material from the Cambridge Greensand Formation, we name a new ophthalmosaurid, Acamptonectes densus gen. et sp. nov. This taxon shares numerous features with Ophthalmosaurus, a genus now restricted to the Callovian–Berriasian interval. Our phylogenetic analysis indicates that Ophthalmosauridae diverged early in its history into two markedly distinct clades, Ophthalmosaurinae and Platypterygiinae, both of which cross the JCB and persist to the late Albian at least. To evaluate the effect of the JCB extinction event on ichthyosaurs, we calculated cladogenesis, extinction, and survival rates for each stage of the Oxfordian–Barremian interval, under different scenarios. The extinction rate during the JCB never surpasses the background extinction rate for the Oxfordian–Barremian interval and the JCB records one of the highest survival rates of the interval. Conclusions/Significance There is currently no evidence that ichthyosaurs were affected by the JCB extinction event, in contrast to many other marine groups. Ophthalmosaurid ichthyosaurs remained diverse from their rapid radiation in the Middle Jurassic to their total extinction at the beginning of the Late Cretaceous

A universal influenza mRNA vaccine candidate boosts T cell responses and reduces zoonotic influenza virus disease in ferrets

Universal influenza vaccines should protect against continuously evolving and newly emerging influenza viruses. T cells may be an essential target of such vaccines, as they can clear infected cells through recognition of conserved influenza virus epitopes. We evaluated a novel T cell-inducing nucleoside-modified messenger RNA (mRNA) vaccine that encodes the conserved nucleoprotein, matrix protein 1, and polymerase basic protein 1 of an H1N1 influenza virus. To mimic the human situation, we applied the mRNA vaccine as a prime-boost regimen in naïve ferrets (mimicking young children) and as a booster in influenza-experienced ferrets (mimicking adults). The vaccine induced and boosted broadly reactive T cells in the circulation, bone marrow, and respiratory tract. Booster vaccination enhanced protection against heterosubtypic infection with a potential pandemic H7N9 influenza virus in influenza-experienced ferrets. Our findings show that mRNA vaccines encoding internal influenza virus proteins represent a promising strategy to induce broadly protective T cell immunity against influenza viruses.</p

Loss of Dnmt3b function upregulates the tumor modifier Ment and accelerates mouse lymphomagenesis

DNA methyltransferase 3B (Dnmt3b) belongs to a family of enzymes responsible for methylation of cytosine residues in mammals. DNA methylation contributes to the epigenetic control of gene transcription and is deregulated in virtually all human tumors. To better understand the generation of cancer-specific methylation patterns, we genetically inactivated Dnmt3b in a mouse model of MYC-induced lymphomagenesis. Ablation of Dnmt3b function using a conditional knockout in T cells accelerated lymphomagenesis by increasing cellular proliferation, which suggests that Dnmt3b functions as a tumor suppressor. Global methylation profiling revealed numerous gene promoters as potential targets of Dnmt3b activity, the majority of which were demethylated in Dnmt3b–/– lymphomas, but not in Dnmt3b–/– pretumor thymocytes, implicating Dnmt3b in maintenance of cytosine methylation in cancer. Functional analysis identified the gene Gm128 (which we termed herein methylated in normal thymocytes [Ment]) as a target of Dnmt3b activity. We found that Ment was gradually demethylated and overexpressed during tumor progression in Dnmt3b–/– lymphomas. Similarly, MENT was overexpressed in 67% of human lymphomas, and its transcription inversely correlated with methylation and levels of DNMT3B. Importantly, knockdown of Ment inhibited growth of mouse and human cells, whereas overexpression of Ment provided Dnmt3b+/+ cells with a proliferative advantage. Our findings identify Ment as an enhancer of lymphomagenesis that contributes to the tumor suppressor function of Dnmt3b and suggest it could be a potential target for anticancer therapies

Mouse Gestation Length Is Genetically Determined

Background: Preterm birth is an enormous public health problem, affecting over 12 % of live births and costing over $26 billion in the United States alone. The causes are complex, but twin studies support the role of genetics in determining gestation length. Despite widespread use of the mouse in studies of the genetics of preterm birth, there have been few studies that actually address the precise natural gestation length of the mouse, and to what degree the timing of labor and birth is genetically determined. Methodology/Principal Findings: To further develop the mouse as a genetic model of preterm birth, we developed a highthroughput monitoring system and measured the gestation length in 15 inbred strains. Our results show an unexpectedly wide variation in overall gestation length between strains that approaches two full days, while intra-strain variation is quite low. Although litter size shows a strong inverse correlation with gestation length, genetic difference alone accounts for a significant portion of the variation. In addition, ovarian transplant experiments support a primary role of maternal genetics in the determination of gestation length. Preliminary analysis of gestation length in the C57BL/6J-Chr # A/J /NaJ chromosome substitution strain (B.A CSS) panel suggests complex genetic control of gestation length. Conclusions/Significance: Together, these data support the role of genetics in regulating gestation length and present th