40 research outputs found

    Odor Fear Conditioning Modifies Piriform Cortex Local Field Potentials Both during Conditioning and during Post-Conditioning Sleep

    Get PDF
    BACKGROUND: Sleep plays an active role in memory consolidation. Sleep structure (REM/Slow wave activity [SWS]) can be modified after learning, and in some cortical circuits, sleep is associated with replay of the learned experience. While the majority of this work has focused on neocortical and hippocampal circuits, the olfactory system may offer unique advantages as a model system for exploring sleep and memory, given the short, non-thalamic pathway from nose to primary olfactory (piriform cortex), and rapid cortex-dependent odor learning. METHODOLOGY/PRINCIPAL FINDINGS: We examined piriform cortical odor responses using local field potentials (LFPs) from freely behaving Long-Evans hooded rats over the sleep-wake cycle, and the neuronal modifications that occurred within the piriform cortex both during and after odor-fear conditioning. We also recorded LFPs from naïve animals to characterize sleep activity in the piriform cortex and to analyze transient odor-evoked cortical responses during different sleep stages. Naïve rats in their home cages spent 40% of their time in SWS, during which the piriform cortex was significantly hypo-responsive to odor stimulation compared to awake and REM sleep states. Rats trained in the paired odor-shock conditioning paradigm developed enhanced conditioned odor evoked gamma frequency activity in the piriform cortex over the course of training compared to pseudo-conditioned rats. Furthermore, conditioned rats spent significantly more time in SWS immediately post-training both compared to pre-training days and compared to pseudo-conditioned rats. The increase in SWS immediately after training significantly correlated with the duration of odor-evoked freezing the following day. CONCLUSIONS/SIGNIFICANCE: The rat piriform cortex is hypo-responsive to odors during SWS which accounts for nearly 40% of each 24 hour period. The duration of slow-wave activity in the piriform cortex is enhanced immediately post-conditioning, and this increase is significantly correlated with subsequent memory performance. Together, these results suggest the piriform cortex may go offline during SWS to facilitate consolidation of learned odors with reduced external interference

    The United States COVID-19 Forecast Hub dataset

    Get PDF
    Academic researchers, government agencies, industry groups, and individuals have produced forecasts at an unprecedented scale during the COVID-19 pandemic. To leverage these forecasts, the United States Centers for Disease Control and Prevention (CDC) partnered with an academic research lab at the University of Massachusetts Amherst to create the US COVID-19 Forecast Hub. Launched in April 2020, the Forecast Hub is a dataset with point and probabilistic forecasts of incident cases, incident hospitalizations, incident deaths, and cumulative deaths due to COVID-19 at county, state, and national, levels in the United States. Included forecasts represent a variety of modeling approaches, data sources, and assumptions regarding the spread of COVID-19. The goal of this dataset is to establish a standardized and comparable set of short-term forecasts from modeling teams. These data can be used to develop ensemble models, communicate forecasts to the public, create visualizations, compare models, and inform policies regarding COVID-19 mitigation. These open-source data are available via download from GitHub, through an online API, and through R packages

    A blood atlas of COVID-19 defines hallmarks of disease severity and specificity.

    Get PDF
    Treatment of severe COVID-19 is currently limited by clinical heterogeneity and incomplete description of specific immune biomarkers. We present here a comprehensive multi-omic blood atlas for patients with varying COVID-19 severity in an integrated comparison with influenza and sepsis patients versus healthy volunteers. We identify immune signatures and correlates of host response. Hallmarks of disease severity involved cells, their inflammatory mediators and networks, including progenitor cells and specific myeloid and lymphocyte subsets, features of the immune repertoire, acute phase response, metabolism, and coagulation. Persisting immune activation involving AP-1/p38MAPK was a specific feature of COVID-19. The plasma proteome enabled sub-phenotyping into patient clusters, predictive of severity and outcome. Systems-based integrative analyses including tensor and matrix decomposition of all modalities revealed feature groupings linked with severity and specificity compared to influenza and sepsis. Our approach and blood atlas will support future drug development, clinical trial design, and personalized medicine approaches for COVID-19

    Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK ‘Alert Level 4’ phase of the B-MaP-C study

    Get PDF
    Abstract: Background: The B-MaP-C study aimed to determine alterations to breast cancer (BC) management during the peak transmission period of the UK COVID-19 pandemic and the potential impact of these treatment decisions. Methods: This was a national cohort study of patients with early BC undergoing multidisciplinary team (MDT)-guided treatment recommendations during the pandemic, designated ‘standard’ or ‘COVID-altered’, in the preoperative, operative and post-operative setting. Findings: Of 3776 patients (from 64 UK units) in the study, 2246 (59%) had ‘COVID-altered’ management. ‘Bridging’ endocrine therapy was used (n = 951) where theatre capacity was reduced. There was increasing access to COVID-19 low-risk theatres during the study period (59%). In line with national guidance, immediate breast reconstruction was avoided (n = 299). Where adjuvant chemotherapy was omitted (n = 81), the median benefit was only 3% (IQR 2–9%) using ‘NHS Predict’. There was the rapid adoption of new evidence-based hypofractionated radiotherapy (n = 781, from 46 units). Only 14 patients (1%) tested positive for SARS-CoV-2 during their treatment journey. Conclusions: The majority of ‘COVID-altered’ management decisions were largely in line with pre-COVID evidence-based guidelines, implying that breast cancer survival outcomes are unlikely to be negatively impacted by the pandemic. However, in this study, the potential impact of delays to BC presentation or diagnosis remains unknown

    Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

    Get PDF
    Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

    The volcanic, magmatic and tectonic setting of the Taupo Volcanic Zone, New Zealand, reviewed from a geothermal perspective

    No full text
    The Taupo Volcanic Zone (TVZ) in the North Island of New Zealand is one of the world’s most spectacularand productive areas of Quaternary silicic volcanism and geothermal manifestations. The TVZ is only thelatest manifestation of NNE–SSW-orientated arcs that have migrated in step-wise fashion to the SSE overthe past ca. 16 Ma. The TVZ began erupting around 2 Ma, with early andesitic volcanism being joined andrapidly swamped by voluminous rhyolitic volcanism. The zone shows a pronounced segmentation intonorthern and southern extremities with andesite composite cones, no calderas and only limited vent-hosted geothermal systems, and a 125 km long rhyolite-dominated central segment. About four timesas much magma is trapped at depth below the central TVZ than is erupted, feeding heat, volatiles andchemicals into 23 geothermal systems with a total of ca. 4.2 GW thermal energy release. The modern(post-61 ka) TVZ is an actively rifting arc, widening at 7 mm/year at the south end to 15 mm/year at theBay of Plenty coastline, with an associated zone of young to active faulting (Taupo Fault Belt: TFB, orthe Taupo Rift), but the axes of the modern TFB and TVZ are offset by 15–20 km through much of thecentral TVZ. Although there is a dominant NNE–SSW tectonic grain within the central TVZ, there arealso influences of deeper basement structures that sometimes extend outside the limits of the zone,such as NW–SE, arc-perpendicular accommodation zones linking local domains of extension as well asN–S orientated structures related to the Hauraki Rift that may control fluid flow into the roots of thegeothermal systems. Models for the geothermal systems favour either a source in a relatively shallowlocalised magmatic intrusion (e.g., Kawerau, Ngatamariki) or treat the systems as reflecting large-scalefluid dynamical instabilities from an evenly heated ‘hot plate’ at ∼7 km depth. Where controls from datingof host lithologies are available, systems at Kawerau and Ngatamariki are seen to represent renewedactivity superimposed on a fossil system fed by past intrusions, and it is unclear what is meant by thelifetime of any single geothermal system. TVZ geothermal systems appear in turn to react too sluggishly torespond to disruptive episodes of volcanism, and recover within geologically short periods of time, as seenat Waimangu and Taupo. In the central TVZ, there are complex inter-relationships between volcanism,magmatism, and tectonism. Magmatism and volcanism are obviously linked, but it is uncertain whyintense magmatism at Taupo and Okataina should yield voluminous rhyolite volcanism, whereas moreintense magmatism in the Taupo-Reporoa Basin has not yielded significant silicic volcanism but insteadfeeds multiple large geothermal systems. The central TVZ is unique for an arc segment in the intensityof its magmatic-volcanic-geothermal flux (matching the Yellowstone system), and the cause(s) of thisuniqueness are not yet established. Any explanation needs to address the segmented nature of the zone,and why the thermal flux should be so geographically and temporally constrained

    Characteristics and variations of sinters in the Coromandel Volcanic Zone: application to epithermal exploration

    No full text
    The Hauraki Goldfield of the Coromandel Volcanic Zone, North Island, New Zealand, hosts up to 19 known siliceous hot spring deposits, or sinters, some directly associated with Au–Ag ore bodies, in a Miocene–Pliocene, sub-aerial, calc-alkaline volcanic arc overlying Jurassic meta-sedimentary basement. Sinters are surface expressions of predominately adularia-sericite epithermal systems, potentially linked to Au–Ag mineralised conduits at depth. They provide a paleosurface marker to determine the level of erosion, and help determine zones of thermal fluid upflow and/or lateral outflow. Mapped sinters of the Coromandel Volcanic Zone are mainly affiliated with rhyolite domes, occur along structural corridors of the volcanic arc, and contain characteristic textures, mineralogy and pathfinder elements typical of near-neutral pH alkali chloride fluid discharge derived from convectively circulating magmatic fluids diluted by meteoric waters. Textures and trace element compositions of the Coromandel sinters are similar to those of the Taupo Volcanic Zone, New Zealand, and the Jurassic Au–Ag mining districts of the Deseado Massif, Argentine Patagonia. Thus, detailed mapping, textural analysis and trace-element studies demonstrate the prospecting potential of siliceous hot spring deposits for locating ore deposits, and in particular to help define proximal to distal positions relative to vent zones at the paleo-surface.Fil: Hamilton, Ayrton. University of Auckland; Nueva ZelandaFil: Campbell, Kathleen. University of Auckland; Nueva ZelandaFil: Rowland, Julie V.. University of Auckland; Nueva ZelandaFil: Barker, Shaun. University of Auckland; Nueva ZelandaFil: Guido, Diego Martin. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Instituto de Recursos Minerales. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto de Recursos Minerales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentin

    Fluid convection stability in faulted rifts: a key to active epithermal mineralisation?

    No full text
    Convective upwelling of meteoric water in the Taupo Volcanic Zone (TVZ), New Zealand, is characterized by extreme heat flows of up to 750 mWm⁻². Despite the extreme heat fluxes and episodic seismic activity and faulting, the intensity and position of upwelling convective zones remains relatively fixed over many thousands of years. Epithermal deposits in the North island of New Zealand occur in Northland, Coromandel and Taupo regions, and all have a close association with Cenozoic volcanic rocks. Gold and silver are present in active geothermal fields and in extinct western geothermal systems of the TVZ. Here we attempt to simulate the effects of permeability contrasts, deformation and heat flow variations to constrain the importance of these different processes in controlling the localization of upflow zones. Given a high heat flow and a permeable homogeneous un-deforming crust our models predict highly vigorous and unstable convection patterns. If the permeability of the crust below 4 km is reduced by at least two orders of magnitude (to simulate greywacke) then a greater stability of convective cells is observed. If a convective heat loss is permitted from the model surface (rather than a fixed surface condition) then even greater stability is obtained. When deformation is introduced this results in an instant disruption of the convective cells, however on cessation of the deformation the convective cells quickly return to a similar position. In the TVZ seismic activity may be too transient to affect the overall location of upwelling convective cells
    corecore