Two faces of perceptual awareness during the attentional blink:Gradual and discrete

In a series of experiments, the nature of perceptual awareness during the attentional blink was investigated. Previous work has considered the attentional blink as a discrete, all-or-none phenomenon, indicative of general access to conscious awareness. Using continuous report measures in combination with mixture modeling, the outcomes showed that perceptual awareness during the attentional blink can be a gradual phenomenon. Awareness was not exclusively discrete, but also exhibited a gradual characteristic whenever the spatial extent of attention induced by the first target spanned more than a single location. Under these circumstances, mental representations of blinked targets were impoverished, but did approach the actual identities of the targets. Conversely, when the focus of attention covered only a single location, there was no evidence for any partial knowledge of blinked targets. These two different faces of awareness during the attentional blink challenge current theories of both awareness and temporal attention, which cannot explain the existence of gradual awareness of targets during the attentional blink. To account for the current outcomes, an adaptive gating model is proposed that casts awareness on a continuum between gradual and discrete, rather than as being of either single kind

SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant

Two faces of perceptual awareness during the attentional blink: Gradual and discrete

In a series of experiments, the nature of perceptual awareness during the attentional blink was investigated. Previous work has considered the attentional blink as a discrete, all-or-none phenomenon, indicative of general access to conscious awareness. Using continuous report measures in combination with mixture modeling, the outcomes showed that perceptual awareness during the attentional blink can be a gradual phenomenon. Awareness was not exclusively discrete, but also exhibited a gradual characteristic whenever the spatial extent of attention induced by the first target spanned more than a single location. Under these circumstances, mental representations of blinked targets were impoverished, but did approach the actual identities of the targets. Conversely, when the focus of attention covered only a single location, there was no evidence for any partial knowledge of blinked targets. These two different faces of awareness during the attentional blink challenge current theories of both awareness and temporal attention, which cannot explain the existence of gradual awareness of targets during the attentional blink. To account for the current outcomes, an adaptive gating model is proposed that casts awareness on a continuum between gradual and discrete, rather than as being of either single kind

Recovering object-location memories after sleep deprivation-induced amnesia

It is well established that sleep deprivation after learning impairs hippocampal memory processes and can cause amnesia. It is unknown, however, whether sleep deprivation leads to the loss of information or merely the suboptimal storage of information that is difficult to retrieve. Here, we show that hippocampal object-location memories formed under sleep deprivation conditions can be successfully retrieved multiple days following training, using optogenetic dentate gyrus (DG) memory engram activation or treatment with the clinically approved phosphodiesterase 4 (PDE4) inhibitor roflumilast. Moreover, the combination of optogenetic DG memory engram activation and roflumilast treatment, 2 days following training and sleep deprivation, made the memory more persistently accessible for retrieval even several days later (i.e., without further optogenetic or pharmacological manipulation). Altogether, our studies in mice demonstrate that sleep deprivation does not necessarily cause memory loss but instead leads to the suboptimal storage of information that cannot be retrieved without drug treatment or optogenetic stimulation. Furthermore, our findings suggest that object-location memories, consolidated under sleep deprivation conditions and thought to be lost, can be made accessible again several days after the learning and sleep deprivation episode, using the clinically approved PDE4 inhibitor roflumilast

Seronegative antibody-mediated neurology after immune checkpoint inhibitors

Checkpoint inhibitor medications have revolutionized oncology practice, but frequently induce immune‐related adverse events. During autoimmune neurology practice over 20 months, we prospectively identified four patients with likely antibody‐mediated neurological diseases after checkpoint inhibitors: longitudinally extensive transverse myelitis, Guillain–Barré syndrome, and myasthenia gravis. All patients shared three characteristics: symptoms commenced 4 weeks after drug administration, responses to conventional immunotherapies were excellent, and autoantibodies traditionally associated with their syndrome were absent. However, serum immunoglobulins from the myelitis and Guillain–Barré syndrome patients showed novel patterns of tissue reactivity. Vigilance is required for antibody‐mediated neurology after checkpoint inhibitor administration. This phenomenon may inform the immunobiology of antibody‐mediated diseases

Seronegative antibody-mediated neurology after immune checkpoint inhibitors

Checkpoint-inhibitor medications have revolutionized oncology practice, but frequently induce immune-related adverse events. During autoimmune neurology practice over 20-months, we prospectively identified four patients with likely antibody-mediated neurological diseases after checkpoint-inhibitors: longitudinally extensive transverse myelitis, Guillain-Barré syndrome and myasthenia gravis. All patients shared three characteristics: symptoms commenced four-weeks after drug administration, responses to conventional immunotherapies were excellent and autoantibodies traditionally associated with their syndrome were absent. Indeed, serum immunoglobulins from the myelitis and Guillain-Barré syndrome patients showed novel patterns of tissue reactivity. Vigilance is required for antibody-mediated neurology after checkpoint-inhibitor administration. This phenomenon may inform the immunobiology of antibody-mediated diseases

Improving primary health care delivery in Bihar, India: Learning from piloting and statewide scale-up of Ananya.

In 2010, the Bill and Melinda Gates Foundation (BMGF) partnered with the Government of Bihar (GoB), India to launch the Ananya program to improve reproductive, maternal, newborn and child health and nutrition (RMNCHN) outcomes. The program sought to address supply- and demand-side barriers to the adoption, coverage, quality, equity and health impact of select RMNCHN interventions. Approaches included strengthening frontline worker service delivery; social and behavior change communications; layering of health, nutrition and sanitation into women's self-help groups (SHGs); and quality improvement in maternal and newborn care at primary health care facilities. Ananya program interventions were piloted in approximately 28 million population in eight innovation districts from 2011-2013, and then beginning in 2014, were scaled up by the GoB across the rest of the state's population of 104 million. A Bihar Technical Support Program provided techno-managerial support to governmental Health as well as Integrated Child Development Services, and the JEEViKA Technical Support Program supported health layering and scale-up of the GoB's SHG program. The level of support at the block level during statewide scale-up in 2014 onwards was approximately one-fourth that provided in the pilot phase of Ananya in 2011-2013. This paper - the first manuscript in an 11-manuscript and 2-viewpoint collection on Learning from Ananya: Lessons for primary health care performance improvement - seeks to provide a broad description of Ananya and subsequent statewide adaptation and scale-up, and capture the background and context, key objectives, interventions, delivery approaches and evaluation methods of this expansive program. Subsequent papers in this collection focus on specific intervention delivery platforms. For the analyses in this series, Stanford University held key informant interviews and worked with the technical support and evaluation grantees of the Ananya program, as well as leadership from the India Country Office of the BMGF, to analyse and synthesise data from multiple sources. Capturing lessons from the Ananya pilot program and statewide scale-up will assist program managers and policymakers to more effectively design and implement RMNCHN programs at scale through technical assistance to governments

Improving primary health care delivery in Bihar, India: Learning from piloting and statewide scale-up of Ananya.

In 2010, the Bill and Melinda Gates Foundation (BMGF) partnered with the Government of Bihar (GoB), India to launch the Ananya program to improve reproductive, maternal, newborn and child health and nutrition (RMNCHN) outcomes. The program sought to address supply- and demand-side barriers to the adoption, coverage, quality, equity and health impact of select RMNCHN interventions. Approaches included strengthening frontline worker service delivery; social and behavior change communications; layering of health, nutrition and sanitation into women's self-help groups (SHGs); and quality improvement in maternal and newborn care at primary health care facilities. Ananya program interventions were piloted in approximately 28 million population in eight innovation districts from 2011-2013, and then beginning in 2014, were scaled up by the GoB across the rest of the state's population of 104 million. A Bihar Technical Support Program provided techno-managerial support to governmental Health as well as Integrated Child Development Services, and the JEEViKA Technical Support Program supported health layering and scale-up of the GoB's SHG program. The level of support at the block level during statewide scale-up in 2014 onwards was approximately one-fourth that provided in the pilot phase of Ananya in 2011-2013. This paper - the first manuscript in an 11-manuscript and 2-viewpoint collection on Learning from Ananya: Lessons for primary health care performance improvement - seeks to provide a broad description of Ananya and subsequent statewide adaptation and scale-up, and capture the background and context, key objectives, interventions, delivery approaches and evaluation methods of this expansive program. Subsequent papers in this collection focus on specific intervention delivery platforms. For the analyses in this series, Stanford University held key informant interviews and worked with the technical support and evaluation grantees of the Ananya program, as well as leadership from the India Country Office of the BMGF, to analyse and synthesise data from multiple sources. Capturing lessons from the Ananya pilot program and statewide scale-up will assist program managers and policymakers to more effectively design and implement RMNCHN programs at scale through technical assistance to governments