Late Peak Research Articles

Measurement and interpretation of spatially registered bar-forces in LC refining

Abstract A high resolution rotary encoder and a piezo electric force sensor are implemented in a 16-inch laboratory-scale low consistency refiner to explore the effect of plate gaps on bar-force profiles. The sensor replaces a short length of a stator bar and measures normal and shear forces applied during the passage of each rotor bar. The rotary encoder data is used to locate the rotor bars relative to the stator bar in which the sensor is located. Previous work with this type of force sensor focuses primarily on the distribution of the maximum force measured during the passage of each rotor bar over the sensor or bar passing event, BPE. In this work, force profiles for bar passing events are registered to the position of rotor bars relative to the stator bar in which the sensor is located. These registered force profiles are measured for a range of plate gaps and two different pulp furnishes. The angular reference provided by the encoder makes it possible to generate mean force profiles. As force data for individual BPEs is highly variable, these mean force profiles have potential to shed light on the fundamental mechanisms of mechanical refining. For large gaps, there is a late peak in the force profiles that occurs toward the end of the bar passing event. For gaps that are less than the critical gap, below which fiber cutting occurs, there is an early peak in the force profiles that occurs at the start of the bar passing event. It is hypothesized that the early peak represents the corner force and, therefore, that corner force is causal in the onset of fiber cutting. To explore this hypothesis, a model is presented connecting corner force and friction force to the progression geometric variables during the bar passing event such as the bar edge length engaged at any point in the bar passing event and the area covered by the rotor bar on the force sensor at any point in the bar passing event.

Late Summer Peak and Scavenging-Dominant Metal Fluxes in Particulate Export Near a Seamount in the Western North Pacific Subtropical Gyre

We measured sedimentation fluxes around JA06 Seamount (Xufu Guyot; 19°30′N, 158°00′E) as part of an environmental baseline survey in Japan’s exploration area for cobalt-rich crusts in the subtropical Northwest Pacific. Sinking particles were collected at the flat top (sediment trap depths: 900 and 1000 m) and northeastern base (sediment trap depths: 1000 and 4720 m) of the seamount from June 2016 to April 2017. Total mass fluxes were very low, with average values of 4.3–4.9 mg m–2 d–1 and 9.3 mg m–2 d–1 in the shallow traps at the flat top and base, respectively, which is consistent with an oligotrophic system. The lower fluxes at the flat top probably reflect lower productivity of siliceous microplankton, such as diatoms. However, we were unable to substantiate any potential mechanisms for this difference in productivity and cannot evaluate whether this is representative of typical conditions. When combined with previous observations at two adjacent seamounts, our results indicate widespread seasonality in sediment fluxes with a peak in late summer (August–September). However, satellite data indicate that summer is the season with the lowest primary production. This discrepancy could be explained either by phytoplankton blooms fueled by symbiotic nitrogen fixation that only cause minor increases in surface-ocean chlorophyll or short-lived blooms induced by passing typhoons under thick cloud cover. At the base site, we also analyzed material and element transport rates from shallow to deep waters. Half of the organic matter and >80% of the carbonate in sinking particles was not degraded in the water column, suggesting that most of the regeneration of these materials occurs near or on the sediment surface. Furthermore, four major processes appeared to control elemental fluxes in the area: lithogenic (Al, Ti, Fe), carbonate (Mg, Ca, Sr), biogenic (+scavenging) (Ni, Zn, Cd, Pb), and scavenging (V, Mn, Co, Cu, rare earth elements) processes. The estimation of excess flux based on the composition of upper continental crust demonstrated that >85% of total Mn, Co, Ni, Cu, Zn, Cd, and Pb fluxes were attributable to scavenging (+biogenic uptake). Scavenging-dominant metal fluxes are likely ubiquitous in the oligotrophic open ocean.

Odor-Induced Saltiness Enhancement: Insights Into The Brain Chronometry Of Flavor Perception

Flavor perception results from the integration of at least odor and taste. Evidence for such integration is that odors can have taste properties (odor-induced taste). Most brain areas involved in flavor perception are high-level areas; however, primary gustatory and olfactory areas also show activations in response to a combination of odor and taste. While the regions involved in flavor perception are now quite well identified, the network's organization is not yet understood. Using a close to real salty soup model with electroencephalography brain recording, we evaluated whether odor-induced saltiness enhancement would result in differences of amplitude and/or latency in late cognitive P3 peak mostly and/or in P1 early sensory peak. Three target solutions were created from the same base of green-pea soup: i) with a “usual” salt concentration (PPS2), ii) with “reduced” salt (PPS1: −50%), and iii) with reduced salt and a “beef stock” odor (PPS1B). Sensory data showed that the beef odor produced saltiness enhancement in PPS1B in comparison to PPS1. As the main EEG result, the late cognitive P3 peak was delayed by 25 ms in the odor-added solution PPS1B compared to PPS1. The odor alone did not explain this peak amplitude and higher latency in the P3 peak. These results support the classical view that high-level integratory areas process odor–taste interactions with potential top-down effects on primary sensory regions.

Impact of chronic sequential LV-RV pacing with cardiac resynchronization therapy for patients with narrower (<130 ms) QRS complexes following evaluation of acute myocardial strain characteristics

Abstract Background Prior studies have shown acute improvement in myocardial strain patterns (SP) and strain rates (SR), left ventricular ejection fraction (LVEF), and long-term clinical improvement by Cardiac Resynchronization Therapy (CRT) preferential LV pacing. This relationship has not been studied in patients (pts) with narrower QRS. Objectives We aimed to evaluate myocardial speckle tracking SP and SR at different VV intervals in pts with narrow (<130 ms) and wide (>130 ms) QRS. Methods We assessed LVEF and speckle tracking myocardial SP and SR as per the American Society of Echocardiography (ASE) Dyssynchrony Writing Group methods in pts with CRT in acute settings at VV0, VV60 and LV-only pacing. For SP assessment, we used Bull's eye format display of the LV segments, and scores for SR, 2 = early stretch, late peak, 1= early stretch, early peak, and 0 = single peak at aortic closure. Results Total cohort of 271 pts; age 69.2±10.3 yrs (mean ± SD), male - 60%, divided into 2 groups; Gp A (QRS <130 ms, n=69) and Gp B (QRS >130 ms, n=202). QRS width and LVEF in Gp A and B were 120.1±12.3 ms and 152.1±12.9 ms, and 22.3±9.4% and 23.3±10.2% respectively. With VV0 increase in LVEF, 67±6.0% from baseline 22.3±9.4% was seen in Gp A compared to 43±6.5% from 23.3±10.2% in Gp B (p<0.01). With VV60 and LV-only pacing further rise in LVEF to 100.0±7.1% and 112.0±7.2% in Gp A and 80.2±8.0% and 93±8.1% in Gp B was seen. (Figure 1). Strain scores at different VV timings in both groups are shown in Table 1. Conclusions In pts with CRT, different VV timings show differences in acute myocardial speckle tracking SP and SR, and LVEF. These changes are markedly favorable with LV-only and sequential LV-RV pacing even in pts with narrower QRS. Our findings support chronic sequential LV-RV pacing programming in CRT pts with narrow QRS. Figure 1 Funding Acknowledgement Type of funding source: None

The clinical significance and prognostic value of early second peak of hs-troponin t in patients successfully treated with primary pci

Abstract Background It was previously demonstrated that in patients with ST segment elevation myocardial infarction (STEMI) high-sensitive troponin-T (Hs-cTnT) makes two peaks. However, the clinical significance of the second peak (early vs late) in patients undergoing successful primary percutaneous intervention (pPCI) is not known. We investigated the role of early second peak on clinical outcomes. Methods Patients who underwent successful pPCI were included. Baseline characteristics, angiographic variables and kinetics of Hs-cTnT levels following pPCI were recorded. Second peak of Hs-cTnT was defined as re-elevation of troponin levels above plateau levels. The second peak of Hs-cTnT is defined as early second peak, if re-elevation is detected earlier than 72 hours after the diagnosis and late second peak, when re-elevation is detected later than 72 hours. Results We included 250 patients divided into two groups; patients with early second peak as group 1 (n=118) and rest of the patients as group 2 (n=132). Baseline characteristics and comorbidities were similar. Peak level of Hs-cTnT, Hs-CRP and pro-BNP levels were significantly lower in group 1 patients. Left ventricular ejection fraction was higher in group 1 patients (47.48±7.7 vs 43.80±9.3, p-value: 0.001). There was no significant difference with respect to new-onset heart failure (24% vs %28, p: 0.503) between groups however cardiac mortality was significantly lower in group 1 patients (%2 vs %11, p: 0.007). Conclusion The early second peak of Hs-cTnT in patients with STEMI is associated with successful reperfusion and predictors of better clinical outcome. Moreover, early second peak of Hs-cTnT is associated with decreased cardiac mortality and has a potential to be used as a marker of good prognosis. Funding Acknowledgement Type of funding source: None

Genetic susceptibility for major depressive disorder associates with trajectories of depressive symptoms across childhood and adolescence.

Early-onset depression during childhood and adolescence is associated with a worse course of illness and outcome than adult onset. However, the genetic factors that influence risk for early-onset depression remain mostly unknown. Using data collected over 13years, we examined whether polygenic risk scores (PRS) that capture genetic risk for depression were associated with depressive symptom trajectories assessed from childhood to adolescence. Data came from the Avon Longitudinal Study of Parents and Children, a prospective, longitudinal birth cohort (analytic sample=7,308 youth). We analyzed the relationship between genetic susceptibility to depression and three time-dependent measures of depressive symptoms trajectories spanning 4-16.5years of age (class, onset, and cumulative burden). Trajectories were constructed using a growth mixture model with structured residuals. PRS were generated from the summary statistics of a genome-wide association study of depression risk using data from the Psychiatric Genomics Consortium, UK Biobank, and 23andMe, Inc. We used MAGMA to identify gene-level associations with these measures. Youth were classified into six classes of depressive symptom trajectories: high/renitent (27.9% of youth), high/reversing (9.1%), childhood decrease (7.3%), late childhood peak (3.3%), adolescent spike (2.5%), and minimal symptoms (49.9%). PRS discriminated between youth in the late childhood peak, high/reversing, and high/renitent classes compared to the minimal symptoms and childhood decrease classes. No significant associations were detected at the gene level. This study highlights differences in polygenic loading for depressive symptoms across childhood and adolescence, particularly among youths with high symptoms in early adolescence, regardless of age-independent patterns.

Diastolic dysfunction in patients with brucellosis despite the absence of infective endocarditis.

Brucellosis is an important systemic infectious disease, especially in developing countries. Every organ and system of the human body can be affected; however, cardiovascular complications of brucellosis are rare. To assess cardiac functions in patients with acute brucellosis without overt cardiac involvement and to answer the following question: Is there any cardiac dysfunction despite the absence of endocarditis in these patients? This cross-sectional study included 67 children with brucellosis and 40 healthy children. We performed a detailed echocardiographic examination in individuals at the beginning of the treatment. Patients with infective endocarditis were excluded from the study. Echocardiography revealed no difference of ejection fraction, mitral and tricuspid annular plane systolic excursion, pulsed-wave Doppler-derived early diastolic peak velocity (E)/late diastolic peak velocity (A) ratios in mitral and tricuspid valves between the two groups. The deceleration time of early mitral inflow was longer in patients with brucellosis. Early diastolic peak velocity of the mitral and tricuspid annuluses obtained by tissue Doppler imaging (Ea) was significantly lower in children with brucellosis. The peak velocity obtained by tissue Doppler imaging during late diastole (Aa), Ea and Ea/Aa ratios in the interventricular septum, left ventricle posterior wall and right ventricle free wall was lower in patients with brucellosis than in the control group. The E/Ea ratio, isovolumic relaxation time, right ventricle and left ventricle myocardial performance indices were higher in patients with brucellosis. Patients with acute brucellosis may have diastolic dysfunction without overt cardiac involvement and infective endocarditis.

Air pollution in Kigali, Rwanda: spatial and temporal variability, source contributions, and the impact of car-free Sundays

Ambient air pollution, particularly fine particulate mass (PM2.5) and ozone (O3), is associated with premature human mortality and other health effects, but monitoring is scarce to non-existent in large parts of Africa. Lower-cost real-time affordable multi-pollutant (RAMP) monitors and a black carbon monitor were deployed in Kigali, Rwanda to fill the air quality data gap here. PM2.5 data were corrected using data from a coincident, short-term campaign that used standard filter-based gravimetry, while gas data were verified by collocation with reference carbon monoxide (CO) and O3 monitors at the Rwanda Climate Observatory at Mt Mugogo, Rwanda. Over March 2017-July 2018, the ambient average PM2.5 in Kigali was 52 µg/m3, significantly higher than World Health Organization (WHO) Interim Target 1. Study average BC was 4 µg/m3, comparable to mid-sized urban areas in India and China and significantly higher than BC in cities in developed countries. Spatial variability across Kigali is limited, while PM2.5 at Mt Mugogo is moderately correlated with PM2.5 in Kigali. A sharp diurnal profile is observed in both PM2.5 and BC, with the Absorption Angstrom Exponent (AAE) indicating that the morning peak is associated with rush-hour traffic-related air pollution (TRAP) while the late evening peak can be attributed to both traffic and domestic biofuel use. PM2.5 in the dry seasons is almost two times that during the following wet seasons while BC is 40-60% higher. Local sources contribute at least half the ambient PM2.5 during wet seasons and one-fourth during dry seasons. Vehicular restrictions on some Sundays appear to reduce PM2.5 and BC by 10-12 µg/m3 and 1 µg/m3 respectively, but this needs further investigation. Dry season ozone in Kigali can exceed WHO guidelines. These lower-cost monitors can play an important role in the continued monitoring essential to track the effectiveness of pollution-control policies recently implemented in Rwanda.

Diurnal Characteristics of Summer Precipitation Over Luzon Island, Philippines

A network of 411 ground stations across Luzon Island, Philippines (12.5–20° N, 119–126.5° E) was used to characterize the diurnal cycles of summer precipitation, in terms of amount (PA), frequency (PF), and intensity (PI), during the southwest monsoon season (SWM; May–September) between 2011 and 2018. In addition to monsoon exposure, the effect of topography on the diurnal cycle of precipitation also was investigated by comparing a valley, plain, west- and east-facing coasts near mountains. Results show that monsoon exposure significantly influenced diurnal precipitation such that PA and PF decreased (PI increased) toward the leeward side of Luzon Island. Most topographies showed late afternoon-early evening peaks; however, the east-facing coast exhibited a late night-early morning peak. Orographic effects led to a high PA over mountains and enhanced the spatiotemporal propagation of PA in monsoon-exposed areas. The first (second) half of the diurnal peak exhibited high PI/low PF (low PI/high PF), suggesting both PI and PF are important indicators of PA. Finally, graded analysis revealed that light precipitation (0.01–2.5 mm h−1) captured overall precipitation trends across Luzon Island, highlighting the importance of this intensity of precipitation. Heavy precipitation (2.5–7.5 mm h−1) peaked in the morning; however, underlying mechanisms remain unknown. The study presents the first examination of the diurnal precipitation cycle in Luzon Island using a dense network of synoptic stations. The study demonstrates the complex effect of topography on precipitation and the importance of the SWM in the diurnal cycle of precipitation.

Longitudinal changes in maternal left atrial volume index and uterine artery pulsatility indices in uncomplicated pregnancy

Data on the relationship between longitudinal changes in maternal volume-dependent echocardiographic parameters and placentation in uncomplicated pregnancy are limited. This study aimed to evaluate changes in volume-dependent echocardiographic parameters in uncomplicated pregnancy to test the hypothesis of the existence of an association between volume-dependent echocardiographic parameters and Doppler ultrasound parameters of fetal circulation and the uterine artery in uncomplicated pregnancy and to establish which of the volume-dependent echocardiographic parameters best depicts volume changes and correlates best with Doppler ultrasound of fetal circulation and the uterine artery in healthy pregnancy. Data from 60 healthy pregnant women were analyzed. A complete echocardiographic study was performed at 11 to 13, 20 to 22, and 30 to 32 weeks' gestation: left ventricular end-diastolic volume, early diastolic peak flow velocity, late diastolic peak flow velocity, left atrial area, and left atrial volume index were assessed. Obstetrical assessment was performed including fetal growth and uterine artery pulsatility index. Fetal well-being was assessed by umbilical and middle cerebral artery blood flow. Serum pregnancy-associated plasma protein A and free β-human chorionic gonadotropin were assessed during the routine first-trimester scan (11-13 weeks' gestation). Left ventricular end-diastolic volume and left atrial area increased significantly between 11 to 13 and 20 to 22 weeks' gestation but not between 20 to 22 and 30 to 32 weeks' gestation. Left atrial volume index measured at 30 to 32 weeks' gestation correlated with uterine artery pulsatility indices in 3 trimesters. Changes in the left atrial volume index between the third and first trimesters correlated significantly with the uterine artery pulsatility index measured at 20 to 22 weeks' gestation (r=-0.345; P=.020) and at 30 to 32 weeks' gestation (r=-0.452; P=.002). Changes in the left atrial volume index between the second and first trimesters significantly correlated with the uterine artery pulsatility index measured in the first trimester (r=-0.316; P=.025). Our study showed that in an uncomplicated pregnancy, among volume-dependent echocardiographic parameters, left atrial volume index increased between both the first and second trimesters and the second and third trimesters and correlated with parameters of Doppler ultrasound of the fetal circulation and the uterine artery. Our results expand on the previous observation on the relationship between maternal cardiovascular adaptation and placentation in women with heart diseases to the population of healthy women with uncomplicated pregnancy.

Neoproterozoic geochronology and provenance of the Adelaide Superbasin

The Adelaide Superbasin (Adelaide Rift Complex, Stuart Shelf, Torrens Hinge Zone, Coombalarnie Platform, and Cambrian Stansbury and Arrowie Basins) is a vast sedimentary basin in southern Australia that initiated due to the break-up of central Rodinia and, evolved into the Australian passive margin on edge of the Pacific Basin. Rocks within it contain evidence for the evolving earth system through the Neoproterozoic, including type sections of the Ediacaran fauna, Sturtian and Marinoan glaciations, and the GSSP for the base of the Ediacaran period. Much research over the last century has unravelled the lithostratigraphy and sedimentology of the basin. Despite this, the rocks are poorly dated, and their sedimentary provenance and link with tectonic geography is poorly known. This poor chronology hampers global and local efforts to gain a detailed understanding and chronological framework of the interplay between tectonics and momentous changes to the earth system during this time. This paper presents a comprehensive database of detrital zircon geochronology and review of geochronology for the Neoproterozoic of the Adelaide Superbasin, highlighting the stratigraphic, and spatial locations of available data.In the north of the basin, zircons were sourced locally in the initial stages of rifting, ca. 830 Ma—from the adjacent Gawler Craton and Curnamona Province. During the late Tonian, detritus was transported along graben from the north-west, from the Musgrave Orogen, as the rift basin developed during the opening of the nascent Pacific Ocean. Cryogenian icesheets punctuate the detrital record with an ephemeral return to more localised rift shoulder sources. In the Ediacaran, there is an increasing influence of younger (<740 Ma) detrital zircon from an enigmatic source that we interpret to be from southern (i.e. Antarctic) sources, with a corresponding shift in the late Mesoproterozoic age peaks, from ca. 1180 Ma to ca. 1090 Ma, and corresponding decrease in older, ca. 1600 Ma, detritus. These changes in sediment source reflect the changing tectonic geography and large-scale environmental influence of the Cryogenian glaciations as the basin evolved from a local rift, to a larger rift basin and finally to a continental margin, with sedimentary input becoming increasingly restricted over time.

Characterizing Weekly Cycles of Particulate Matter in a Coastal Megacity: The Importance of a Seasonal, Size‐Resolved, and Chemically Speciated Analysis

AbstractWe present the first study of the weekly cycles (WCs) of chemically speciated and size‐resolved particulate matter (PM) in Metro Manila, Philippines, a coastal megacity located within a highly complex meteorological environment that is subject to both anthropogenic and natural sources. To measure PM, Micro‐Orifice Uniform Deposit Impactors (MOUDIs) were deployed in Metro Manila from August 2018 to October 2019 and samples were analyzed for ionic and elemental species, including black carbon (BC). The WC in Metro Manila varied remarkably across seasons, linked to shifts in meteorology, transport, and aerosol source. Identified aerosol sources were traffic, local and regional burning, dust, sea salt, and secondary aerosol formation. Direct emissions induced a late workweek peak, while secondary aerosol formation led to a weekend peak in response to precursor buildup mainly from traffic. Seasonal analysis revealed that local burning from solid waste management and agricultural fires induced a strong WC peak while regional burning emissions from the Maritime Continent (MC) and possibly the Asian continent elevated seasonal baseline concentrations of the WC. BC showed a seasonally persistent WC, consistent in magnitude, weekly peak timing, and particle size. The dominant submicrometer WC and the contribution of BC across seasons have important ramifications on public health and policymaking, which are also discussed. As many of the observed WC patterns are undetectable when using only bulk PM, this study demonstrates that a seasonal, size‐resolved, and chemically speciated characterization is required to more fully understand the driving mechanisms governing WCs.

Activity pattern, budget and diurnal rhythmicity of the brown-throated three-toed sloth (Bradypus variegatus) in northeastern Brazil

Previous studies exploring the rhythmic activity of sloths of the Bradypus genus in undisturbed forests revealed cathemeral patterns of activity. In the current study we wished to examine sloth behavior in a highly disturbed secondary forest habitat. We evaluated activity pattern, time budget and rhythmic activities of brown-throated three-toed sloths (B. variegatus) living in the border of a highly disturbed forest fragment in northeastern Brazil. Three adults (2 females and 1 male) and 2 infants were studied over 29 days. Observational data were collected in 15 min increments over the 24-h day in the following categories: resting, moving, travelling, eating and grooming. Time series data were subjected to X2 periodogram, Fourier (Fast Fourier Transformation, FFT), cosinor and CircWave circadian rhythm analysis, and revealed significant 24-h rhythms in all behaviors in most circumstances. Unlike sloths located in an undisturbed forest, this population exhibited primarily diurnal activity patterns of behavior, with the center of gravity for each behavior occurring in the middle of the day. Furthermore, several behaviors were expressed in a bimodal pattern, with a morning and a late afternoon peak of activity. These data suggest that with decreased predator presence and with a more ubiquitous food source, sloths adjust their temporal niche to daytime.

Can myocardial performance index predict early cardiac risks in erectile dysfunction?

Aim Myocardial performance index (MPI) is an easy-to-apply and non-invasive method that shows both systolic and diastolic functions of the heart. In this study, it was aimed to evaluate the relationship between erectile dysfunction (ED) and MPI. Methods: The study included 45 male patients admitted to the urology outpatient clinic for ED and 48 healthy male volunteers. Echocardiographic evaluation of all participants was performed. Isovolumetric contraction time (IVCT), isovolumetric relaxation time (IVRT) and ejection time (ET) were measured. MPI was calculated using the IVCT + IVRT/ET formula. Results: The average age of the study population was 50 ± 5.3. Early diastolic mitral inflow (E)/late diastolic mitral inflow (A) ratio was significantly lower in the ED group (p ≤ 0.05). In the TDI evaluation between the groups, while early diastolic mitral annular velocity (Em) was significantly higher in the ED group, there was no significant difference in late diastolic mitral annular velocity (Am) and systolic peak velocities (Sm) (p < 0.01 and p = 0.417 and p = 0.092, respectively). While IVRT was significantly lower in the ED group (p < 0.05), there was no significant difference in IVCT and ET (p = 311 and p = 0.261, respectively). MPI was statistically significantly higher in the ED group (p < 0.05). Conclusion: ED has been found to affect MPI. This parameter, which is easily and non-invasively measured, can be used to predict the risk of CVDs in ED.

Late effects of adjuvant chemotherapy adumbrate dormancy complexity in breast cancer

BackgroundDormant avascular micrometastases and single, or small groups of, non-proliferating cells are currently assumed to explain the multipeak dynamics of distant metastases (DM) following primary breast cancer surgical removal. MethodsThe hazard rate pattern for DM was analysed in 1518 premenopausal node-positive patients, enrolled in a series of randomized clinical trials on early breast cancer, which were carried out in Italy and Belgium. Patients underwent surgery alone (n = 397) or surgery plus adjuvant chemotherapy (n = 1121) and the minimal follow up was 15 years. ResultsThe DM hazard rate for patients undergoing surgery alone displayed two early sharp peaks at 9 and 33 months, a wide intermediate one spanning from about 50 to 90 months and a late peak at 115–120 months. Adjuvant chemotherapy was associated with a prominent reduction of the two early peaks leaving a residual one at about 18 months and a reduction of the intermediate peak leaving two small peaks at about 50 and 80 months. The late peak remained unchanged. ConclusionsPresent results reveal the ability of adjuvant chemotherapy to reduce not only the rate of early relapses, but also the rate of intermediate relapses at about the sixth year of follow up. Adjuvant chemotherapy is not impacting on the development of metastases underlying the late peak detected at the tenth year. These findings suggest the existence of a previously unknown dormancy state that, at the primary tumour surgical removal, results in evolving chemo-sensitive metastatic processes, and, moreover, of a later chemo-refractory dormancy state.

Surface microtextures and new U–Pb dating of detrital zircons from the Eocene Strihovce sandstones in the Magura Nappe of the External Western Carpathians: implications for their provenance

Heavy mineral morphological, chemical and isotopic features are strong discriminative parameters in provenance studies. This paper focuses on the micro-textural signatures of detrital zircon grains obtained by scanning electron microscope (SEM) and U–Pb geochronological dating from the Strihovce Formation sandstones of the Magura Nappe in the External Western Carpathians. Our focus provides an important contribution to understanding the provenance of these sedimentary rocks. Although the SEM images reveal few dissolution features, they highlight many marks of mechanical processes which occur during detrital zircon transport. The detrital zircon U–Pb ages range from Mesoarchean–Neoproterozoic through Cambrian to Permian and Late Cretaceous. The pronounced peak at approximately 480 Ma Ordovician indicates the culmination of the peri-Gondwanan magmatic event. In conjunction with Archean to Proterozoic zircon inheritance, it implies Cadomian affinity of the potential source terranes which supplied the Magura Basin. The approximate ages of 379 Ma for the Late Devonian peak and 264 Ma for the Permian relate to widespread magmatism and/or rhyolite volcanism. These sources could be associated with the Carpathian basement units and the Apuseni terranes of the Tisza/Dacia mega-units. Most importantly, the sub-hedral Proterozoic zircons may signal the input of ‘first-cycle’ material from relatively closer surroundings, including the South-Magura Ridge to the Magura Basin.

Bone-conducted vestibular and stretch reflexes in human neck muscles.

In normal humans, tapping the forehead produces a neck muscle reflex that is used clinically to test vestibular function, the cervical vestibular evoked myogenic potential (cVEMP). As stretch receptors can also be activated by skull taps, we investigated the origin of the early and late peaks of the bone-conducted cVEMP. In twelve normal participants, we differentially stimulated the vestibular and neck stretch receptors by applying vibration to the forehead (activating both vestibular and stretch receptors) and to the sternum (activating mainly stretch receptors). Patients with bilateral vestibulopathy (BVP; n = 26) and unilateral vestibular loss (uVL; n = 17) were also investigated for comparison. Comparison of peaks in normal subjects suggested that the early peaks were vestibular-dependent, while the later peaks had mixed vestibular and stretch input. The late peaks were present but small (1.1 amplitude ratio) in patients with BVP and absent VEMPs, confirming that they do not strictly depend on vestibular function, and largest in age-matched controls (1.5 amplitude ratio, p = 0.049), suggesting that there is an additional vestibular reflex at this latency (approx. 30ms). Patients with uVL had larger late peaks on the affected than the normal side (1.4 vs 1.0 amplitude ratio, p = 0.034). The results suggest that the early responses in SCM to skull vibration in humans are vestibular-dependent, while there is a late stretch reflex bilaterally and a late vestibular reflex in the contralateral muscle.

Muscle-specific modulation of indirect inputs to primary motor cortex during action observation.

Single-pulse transcranial magnetic stimulation (spTMS) studies report that movement observation facilitates corticospinal excitability in primary motor cortex (M1) in a muscle-specific manner. However, motor evoked potentials (MEPs) elicited by spTMS are known to reflect the summation of several descending volleys in corticospinal neurons which are evoked via mono- and polysynaptic inputs (so-called indirect waves or I-waves). It is unclear which of these components contribute to the muscle-specific modulation of M1 during action observation. The interactions between different I-waves are reflected in the facilitatory peaks elicited with a short-intracortical facilitation (SICF) protocol when two pulses are sent to M1 at precise intervals (i.e., 1.3, 2.5 or 4.1ms). Here, we explored the modulation of early and late SICF peaks during action observation by measuring highly specific MEP amplitude changes measured in two muscles (index, FDI and little finger, ADM) while participants observed two different actions (precision and whole-hand grip). Our results demonstrate that both early (1.3ms) and late (2.5 and 4.1ms) SICF peaks are modulated in the context of movement observation. However, only the second peak (ISI 2.5ms) was significantly associated with the muscle-specific modulation of corticospinal excitability as measured with spTMS. This late SICF peak is believed to reflect the activity cortico-cortical pathways involved in the facilitation of muscle-specific representations in M1. Thus, our findings suggest that movement observation leads to widespread activation of different neural circuits within M1, including those mediating cortico-cortical communication.

Atrial function in Fontan patients assessed by CMR: Relation with exercise capacity and long-term outcomes

ObjectiveTo assess the role of atrial function on exercise capacity and clinical events in Fontan patients. DesignWe included 96 Fontan patients from 6 tertiary centers, aged 12.8 (IQR 10.1–15.6) years, who underwent cardiac magnetic resonance imaging and cardiopulmonary exercise testing within 12 months of each other from 2004 to 2017. Intra-atrial lateral tunnel (ILT) and extracardiac conduit (ECC) patients were matched 1:1 with regard to age, gender and dominant ventricle.The pulmonary venous atrium was manually segmented in all phases and slices. Atrial function was assessed by volume-time curves. Furthermore, atrial longitudinal and circumferential feature tracking strain was assessed.We determined the relation between atrial function and exercise capacity, assessed by peak oxygen uptake and VE/VCO2 slope, and events (mortality, listing for transplant, re-intervention, arrhythmia) during follow-up. ResultsAtrial maximal and minimal volumes did not differ between ILT and ECC patients. ECC patients had higher reservoir function (21.1 [16.4–28.0]% vs 18.2 [10.9–22.2]%, p = .03), lower conduit function and lower total circumferential strain (13.8 ± 5.1% vs 18.0 ± 8.7%, p = .01), compared to ILT patients.Only for ECC patients, a better late peak circumferential strain rate predicted better VE/VCO2 slope. No other parameter of atrial function predicted peak oxygen uptake or VE/VCO2 slope.During a median follow-up of 6.2 years, 42 patients reached the composite end-point. No atrial function parameters predicted events during follow-up. ConclusionsECC patients have higher atrial reservoir function and lower conduit function. Atrial function did not predict exercise capacity or events during follow-up.

The effects of NMDA receptor blockade on TMS-evoked EEG potentials from prefrontal and parietal cortex

Measuring the brain’s response to transcranial magnetic stimulation (TMS) with electroencephalography (EEG) offers unique insights into the cortical circuits activated following stimulation, particularly in non-motor regions where less is known about TMS physiology. However, the mechanisms underlying TMS-evoked EEG potentials (TEPs) remain largely unknown. We assessed TEP sensitivity to changes in excitatory neurotransmission mediated by n-methyl-d-aspartate (NMDA) receptors following stimulation of non-motor regions. In fourteen male volunteers, resting EEG and TEPs from prefrontal (PFC) and parietal (PAR) cortex were measured before and after administration of either dextromethorphan (NMDA receptor antagonist) or placebo across two sessions in a double-blinded pseudo-randomised crossover design. At baseline, there were amplitude differences between PFC and PAR TEPs across a wide time range (15–250 ms), however the signals were correlated after ~80 ms, suggesting early peaks reflect site-specific activity, whereas late peaks reflect activity patterns less dependent on the stimulated sites. Early TEP peaks were not reliably altered following dextromethorphan compared to placebo, although findings were less clear for later peaks, and low frequency resting oscillations were reduced in power. Our findings suggest that early TEP peaks (<80 ms) from PFC and PAR reflect stimulation site specific activity that is largely insensitive to changes in NMDA receptor-mediated neurotransmission.