Topography of Cortical Activation Differs for Fundamental and Harmonic Frequencies of the Steady-State Visual-Evoked Responses. An EEG and PET H15 2 O Study

In humans, visual flicker stimuli of graded frequency (2--90 Hz) elicit an electroencephalographic (EEG) steady-state visual-evoked response (SSVER) with the same fundamental frequency as the stimulus and, in addition, a series of harmonic responses. The fundamental component of the SSVER is generated by increased synaptic activity in primary visual cortex (V1). We set out to determine the cortical origin of the harmonic responses in humans. For this purpose, we recorded the SSVERs at 5 different frequencies (5, 10, 15, 25, and 40 Hz) and measured regional cerebral blood flow (rCBF) with positron emission tomography-H15 2 O at rest and during visual stimulation at the same frequencies. The rCBF contrast weighted by the amplitude of the SSVERs first harmonics showed activation of a swath of cortex perpendicular to V1, including mostly the inferior half of the parietooccipital sulcus. This area overlapped minimally with the primary visual cortex activated by the fundamental frequency. A different method, estimating EEG cortical source current density with lowresolution brain electromagnetic tomography, gave the same results. Our finding suggests that the inferior portion of the banks of the parieto-occipital sulci contains association visual cortex involved in the procparieto-occipital sulcus

Human Cerebral Activation during Steady-State Visual-Evoked Responses

Flicker stimuli of variable frequency (2-90 Hz) elicit a steady-state visual-evoked response (SSVER) in the electroencephalogram (EEG) with the same frequency as the stimulus. In humans, the amplitude of this response peaks at approximately 15 Hz, decreasing at higher stimulation frequencies. It was not known whether this peak response corresponds to increased synaptic activity in the visual cortex or to other mechanisms [for instance, the temporal coherence (phase summation) of evoked responses]. We studied the SSVER in 16 normal volunteers by means of visual stimulation at 14 different frequencies (from 5 to 60 Hz) while recording the EEG. In nine subjects of the group, we measured regional cerebral blood flow (rCBF) with positron emission tomography (PET)-H2(15)O at rest and during visual stimulation at five different frequencies: 5, 10, 15, 25, and 40 Hz. We confirmed that the amplitude of the SSVER in occipital regions peaks at 15 Hz stimulation. Applying to the PET rCBF data a contrast weighted by the amplitude of the SSVER, we determined that the primary visual cortex rCBF follows an activation pattern similar to the SSVER. This finding suggests that the amplitude of the SSVER corresponds to increased synaptic activity, specifically in Brodmann's area 17. Additionally, this study showed that visual stimulation at 40 Hz causes selective activation of the macular region of the visual cortex, and that a region in the dorsal aspect of the Crus I lobule of the left cerebellar hemisphere is activated during repetitive visual stimulation

Expression of B-nerve growth factor in rabbit male tract and seminal plasma

Nerve growth factor (NGF) has been recently identified as an ovulation inductor factor (OIF) in the seminal plasma (SP) (Ratto et al. PNAS 2012; 109:15042-7). The presence of OIF in rabbit has been suggested but this protein has not yet been identified. Our aim was to study the mRNA expression in the rabbit male reproductive tract and to identify the protein β-NGF in the SP

A view of the Brazil-Malvinas confluence, March 2015

The encountering of the subtropical Brazil Current (BC) and the subantarctic Malvinas Current (MC) along the western margin of the Argentine Basin forms the Brazil-Malvinas Confluence (BMC), one of the most intense open-ocean fronts in the world ocean and a site for the formation of intermediate water masses. Here, we provide a comprehensive description of the BMC based on physical and biogeochemical data – hydrographic stations, profiling floats and subsurface drifters – gathered in March 2015. We use these data in order to characterize the impinging and outflowing currents and to describe the cross- and along-frontal thermohaline structure. In addition, we compare the in-situ measurements with both climatological data and the Mercator Ocean eddy-resolving reanalysis. The hydrographic sections illustrate the contrasting properties between the two western boundary currents: warm, salty, nutrient- and oxygen-poor oligotrophic subtropical waters carried southward by the BC and the cold, fresh, oxygen- and nutrient-rich subantarctic waters carried northward by the MC. The frontal system is also characterized by the presence of thermohaline intrusions, with the cross-frontal gradients and along-front velocities sharpening as the colliding currents shape the frontal system. We also observe brackish waters spreading on top of the frontal jet as a result of both the confluence dynamics and off-shelf advection favored by north-easterly winds. These low-salinity waters are positively correlated with surface ageostrophic speeds over the frontal jet. The cruise data illustrates the high regional and mesoscale variability as compared with climatological conditions, and further document the submesoscale subsurface complexity, which is not properly captured by available operational models.Fil: Orúe Echevarría, Dorleta. Consejo Superior de Investigaciones Científicas. Instituto de Ciencias del Mar; EspañaFil: Pelegrí, Josep L.. Consejo Superior de Investigaciones Científicas. Instituto de Ciencias del Mar; EspañaFil: Alonso González, Iván J.. Oceomic, Marine Bio And Technology S.L; EspañaFil: Benítez Barrios, Verónica M.. Oceomic, Marine Bio And Technology S.L; EspañaFil: Emelianov, Mikhail. Consejo Superior de Investigaciones Científicas. Instituto de Ciencias del Mar; EspañaFil: García Olivares, Antonio. Consejo Superior de Investigaciones Científicas. Instituto de Ciencias del Mar; EspañaFil: Gasser i Rubinat, Marc. Consejo Superior de Investigaciones Científicas. Instituto de Ciencias del Mar; EspañaFil: De La Fuente, Patricia. Consejo Superior de Investigaciones Científicas. Instituto de Ciencias del Mar; EspañaFil: Herrero, Carmen. Consejo Superior de Investigaciones Científicas. Instituto de Ciencias del Mar; EspañaFil: Isern Fontanet, Jordi. Consejo Superior de Investigaciones Científicas. Instituto de Ciencias del Mar; EspañaFil: Masdeu Navarro, Marta. Consejo Superior de Investigaciones Científicas. Instituto de Ciencias del Mar; EspañaFil: Peña Izquierdo, Jesús. Consejo Superior de Investigaciones Científicas. Instituto de Ciencias del Mar; EspañaFil: Piola, Alberto Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones del Mar y la Atmósfera. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones del Mar y la Atmósfera; ArgentinaFil: Ramírez Garrido, Sergio. Consejo Superior de Investigaciones Científicas. Instituto de Ciencias del Mar; EspañaFil: Rosell Fieschi, Miquel. Consejo Superior de Investigaciones Científicas. Instituto de Ciencias del Mar; EspañaFil: Salvador, Joaquín. Consejo Superior de Investigaciones Científicas. Instituto de Ciencias del Mar; EspañaFil: Saraceno, Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones del Mar y la Atmósfera. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones del Mar y la Atmósfera; Argentina. Universidad de Barcelona; EspañaFil: Valla, Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ciencias de la Atmósfera y los Océanos; ArgentinaFil: Vallès Casanova, Ignasi. Consejo Superior de Investigaciones Científicas. Instituto de Ciencias del Mar; EspañaFil: Vidal, Montserrat. Universidad de Barcelona; Españ

P1‐349: Advancing Clinical And Biomarker Research In Ad: The Lead Study

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152716/1/alzjjalz201906904.pd

Cumulative Prognostic Score Predicting Mortality in Patients Older Than 80 Years Admitted to the ICU.

OBJECTIVES: To develop a scoring system model that predicts mortality within 30 days of admission of patients older than 80 years admitted to intensive care units (ICUs). DESIGN: Prospective cohort study. SETTING: A total of 306 ICUs from 24 European countries. PARTICIPANTS: Older adults admitted to European ICUs (N = 3730; median age = 84 years [interquartile range = 81-87 y]; 51.8% male). MEASUREMENTS: Overall, 24 variables available during ICU admission were included as potential predictive variables. Multivariable logistic regression was used to identify independent predictors of 30-day mortality. Model sensitivity, specificity, and accuracy were evaluated with receiver operating characteristic curves. RESULTS: The 30-day-mortality was 1562 (41.9%). In multivariable analysis, these variables were selected as independent predictors of mortality: age, sex, ICU admission diagnosis, Clinical Frailty Scale, Sequential Organ Failure Score, invasive mechanical ventilation, and renal replacement therapy. The discrimination, accuracy, and calibration of the model were good: the area under the curve for a score of 10 or higher was .80, and the Brier score was .18. At a cut point of 10 or higher (75% of all patients), the model predicts 30-day mortality in 91.1% of all patients who die. CONCLUSION: A predictive model of cumulative events predicts 30-day mortality in patients older than 80 years admitted to ICUs. Future studies should include other potential predictor variables including functional status, presence of advance care plans, and assessment of each patient's decision-making capacity

Sepsis at ICU admission does not decrease 30-day survival in very old patients: a post-hoc analysis of the VIP1 multinational cohort study.

BACKGROUND: The number of intensive care patients aged ≥ 80 years (Very old Intensive Care Patients; VIPs) is growing. VIPs have high mortality and morbidity and the benefits of ICU admission are frequently questioned. Sepsis incidence has risen in recent years and identification of outcomes is of considerable public importance. We aimed to determine whether VIPs admitted for sepsis had different outcomes than those admitted for other acute reasons and identify potential prognostic factors for 30-day survival. RESULTS: This prospective study included VIPs with Sequential Organ Failure Assessment (SOFA) scores ≥ 2 acutely admitted to 307 ICUs in 21 European countries. Of 3869 acutely admitted VIPs, 493 (12.7%) [53.8% male, median age 83 (81-86) years] were admitted for sepsis. Sepsis was defined according to clinical criteria; suspected or demonstrated focus of infection and SOFA score ≥ 2 points. Compared to VIPs admitted for other acute reasons, VIPs admitted for sepsis were younger, had a higher SOFA score (9 vs. 7, p < 0.0001), required more vasoactive drugs [82.2% vs. 55.1%, p < 0.0001] and renal replacement therapies [17.4% vs. 9.9%; p < 0.0001], and had more life-sustaining treatment limitations [37.3% vs. 32.1%; p = 0.02]. Frailty was similar in both groups. Unadjusted 30-day survival was not significantly different between the two groups. After adjustment for age, gender, frailty, and SOFA score, sepsis had no impact on 30-day survival [HR 0.99 (95% CI 0.86-1.15), p = 0.917]. Inverse-probability weight (IPW)-adjusted survival curves for the first 30 days after ICU admission were similar for acute septic and non-septic patients [HR: 1.00 (95% CI 0.87-1.17), p = 0.95]. A matched-pair analysis in which patients with sepsis were matched with two control patients of the same gender with the same age, SOFA score, and level of frailty was also performed. A Cox proportional hazard regression model stratified on the matched pairs showed that 30-day survival was similar in both groups [57.2% (95% CI 52.7-60.7) vs. 57.1% (95% CI 53.7-60.1), p = 0.85]. CONCLUSIONS: After adjusting for organ dysfunction, sepsis at admission was not independently associated with decreased 30-day survival in this multinational study of 3869 VIPs. Age, frailty, and SOFA score were independently associated with survival

Relationship between the Clinical Frailty Scale and short-term mortality in patients ≥ 80 years old acutely admitted to the ICU: a prospective cohort study.

BACKGROUND: The Clinical Frailty Scale (CFS) is frequently used to measure frailty in critically ill adults. There is wide variation in the approach to analysing the relationship between the CFS score and mortality after admission to the ICU. This study aimed to evaluate the influence of modelling approach on the association between the CFS score and short-term mortality and quantify the prognostic value of frailty in this context. METHODS: We analysed data from two multicentre prospective cohort studies which enrolled intensive care unit patients ≥ 80 years old in 26 countries. The primary outcome was mortality within 30-days from admission to the ICU. Logistic regression models for both ICU and 30-day mortality included the CFS score as either a categorical, continuous or dichotomous variable and were adjusted for patient's age, sex, reason for admission to the ICU, and admission Sequential Organ Failure Assessment score. RESULTS: The median age in the sample of 7487 consecutive patients was 84 years (IQR 81-87). The highest fraction of new prognostic information from frailty in the context of 30-day mortality was observed when the CFS score was treated as either a categorical variable using all original levels of frailty or a nonlinear continuous variable and was equal to 9% using these modelling approaches (p < 0.001). The relationship between the CFS score and mortality was nonlinear (p < 0.01). CONCLUSION: Knowledge about a patient's frailty status adds a substantial amount of new prognostic information at the moment of admission to the ICU. Arbitrary simplification of the CFS score into fewer groups than originally intended leads to a loss of information and should be avoided. Trial registration NCT03134807 (VIP1), NCT03370692 (VIP2)