Surrogate gradient learning in spiking networks trained on event-based cytometry dataset.

Spiking neural networks (SNNs) are bio-inspired neural networks that - to an extent - mimic the workings of our brains. In a similar fashion, event-based vision sensors try to replicate a biological eye as closely as possible. In this work, we integrate both technologies for the purpose of classifying micro-particles in the context of label-free flow cytometry. We follow up on our previous work in which we used simple logistic regression with binary labels. Although this model was able to achieve an accuracy of over 98%, our goal is to utilize the system for a wider variety of cells, some of which may have less noticeable morphological variations. Therefore, a more advanced machine learning model like the SNNs discussed here would be required. This comes with the challenge of training such networks, since they typically suffer from vanishing gradients. We effectively apply the surrogate gradient method to overcome this issue achieving over 99% classification accuracy on test data for a four-class problem. Finally, rather than treating the neural network as a black box, we explore the dynamics inside the network and make use of that to enhance its accuracy and sparsity.

Effect of jump exercise training on long-term head-down bed rest-induced cerebral blood flow responses in arteries and veins.

NEW FINDINGS: What is the central question of this study? What is the effect of an exercise countermeasure on microgravity-induced change in cerebral blood flow? What is the main finding and its importance? Jump exercise training as a countermeasure did not modify the heterogeneous cerebral blood flow response to head-down bed rest, suggesting that this method is effective in preventing cardiovascular system deconditioning but is not good for cerebral haemodynamics. ABSTRACT: This study aimed to examine the effect of an exercise countermeasure on cerebral blood flow (CBF) response to long-term -6° head-down bed rest (HDBR) in all cerebral arteries and veins. Twenty male volunteers were exposed to HDBR for 60 days with (training group, n = 10) or without (control group, n = 10) jump exercise training as a countermeasure to spaceflight. The blood flow in the neck conduit arteries (internal carotid and vertebral artery; ICA and VA) and veins (internal jugular and vertebral veins; IJV and VV) was measured, using ultrasonography before (baseline) HDBR, on the 30th and 57th day of HDBR. Long-term HDBR causes a heterogeneous CBF response between the anterior and the posterior brain or between arteries and veins. Long-term HDBR decreased anterior cerebral arterial and venous blood flow, while posterior cerebral arterial and venous blood flows were well maintained. However, exercise jump training did not change each arterial and venous CBF responses to HDBR (control vs. training; ICA, P = 0.643; VA, P = 0.542; external carotid artery, P = 0.644; IJV, P = 0.980; VV, P = 0.999). These findings suggest that jump exercise training did not modify the heterogeneous CBF response to long-term HDBR.

[Drug provocation tests to identify analgesic alternatives for an infant with Stevens-Johnson syndrome caused by ibuprofen-acetaminophen]. / Provocación farmacológica para identificar alternativas analgésicas en infante con síndrome de Stevens-Johnson por ibuprofeno-acetaminofén.

BACKGROUND: The Stevens-Johnson syndrome is a serious skin reaction to drugs, and it is potentially life-threatening. Its handling involves the strict restriction of the drug involved, as well as of the drugs that are similar or structurally related. CASE REPORT: A two-year and eight-month old girl with Stevens-Jonson syndrome that was caused by acetaminophen and ibuprofen. Due to the total restriction of non-steroidal anti-inflammatory drugs, and with the purpose of establishing antipyretic alternatives, an oral provocation test was carried out with the usual dose of oral nimesulide, which was negative for both immediate and late reactions. In order to offer a parenteral alternative, a provocation test was carried out with intravenous dipyrone, with in-hospital monitoring for 48 hours in an administration protocol of 10, 30 and 60 %; one dose per hour, for a total of 400 mg. The provocation test was negative for both immediate and late reactions. Oral nimesulide or parenteral dipyrone were prescribed upon requiring analgesic, anti-inflammatory, or antipyretic medication. CONCLUSION: At a pediatric age, febrile symptoms are common and controlling them is fundamental; such that if an allergy to non-steroidal anti-inflammatory drugs and acetaminophen is identified in an infant, an affectation on the quality of life will be entailed.

Antecedentes: El síndrome de Stevens-Johnson es una reacción farmacológica cutánea grave, potencialmente mortal. Su manejo incluye estricta restricción del medicamento implicado y de los fármacos estructuralmente relacionados o similares. Caso clínico: Niña de dos años y ocho meses quien presentó síndrome de Stevens-Johnson desencadenado por acetaminofén e ibuprofeno. Debido a la restricción total de antiinflamatorios no esteroideos y con el fin de establecer alternativas antipiréticas, se realizó provocación oral con dosis usual de nimesulida oral, la cual fue negativa para reacciones inmediatas y tardías. Para ofrecer una alternativa parenteral, se efectuó prueba de provocación con dipirona intravenosa, con vigilancia intrahospitalaria por 48 horas en un protocolo de administración de 10, 30 y 60 %, una dosis cada hora, para un total de 400 mg. La prueba de provocación fue negativa para reacciones inmediatas y tardías. Se indicó nimesulida oral o dipirona oral o parenteral en caso de requerir medicación analgésica, antiinflamatoria o antipirética. Conclusión: En la infancia, los cuadros febriles son comunes y el control de este síntoma es fundamental, de tal forma que si en un infante se identifica alergia a los antiinflamatorios no esteroideos y al acetaminofén, eso supondrá afectación en la calidad de vida.

Arterial and venous cerebral blood flow responses to long-term head-down bed rest in male volunteers.

NEW FINDINGS: What is the central question of this study? A heterogeneous cerebral blood flow (CBF) response in the cerebral arteries has been demonstrated in several physiological conditions, and it might be attributable to different physiological properties. However, the whole cerebral haemodynamic response to weightlessness remains unknown. What is the main finding and its importance? Long-term head-down bed rest caused a heterogeneous CBF response between the anterior and posterior cerebral arteries and between the cerebral arteries and veins. Especially, in contrast to the anterior cerebral circulation, the posterior arterial and venous CBFs were well maintained throughout weightlessness. ABSTRACT: In this study, we investigated the whole cerebral haemodynamic response to long-term head-down bed rest (HDBR). We hypothesized that long-term exposure to weightlessness influences cerebral blood flow (CBF) or CBF distribution among cerebral arteries and veins because of the different physiological roles of each cerebral vessel. To test this hypothesis, 10 male volunteers were exposed to -6 deg HDBR for 60 days. Blood flows in the internal carotid artery, external carotid artery and vertebral artery or internal jugular vein and vertebral vein were measured using ultrasonography before and on days 30 and 57 of the HDBR. The internal carotid artery blood flow was reduced on day 30 (P = 0.019) and had returned to the baseline level by day 57. In contrast, the vertebral artery blood flow remained unaltered throughout the HDBR (P = 0.626). The internal jugular vein blood flow was reduced on day 30 (P = 0.009), whereas the vertebral vein blood flow remained unaltered (P = 0.397). These findings suggest that long-term HDBR causes a heterogeneous CBF response between the anterior and posterior cerebral circulation in the both arteries and veins. The posterior arterial and venous CBFs were well maintained throughout HDBR, and these CBF responses to HDBR were different from the anterior cerebral circulation.

Long-duration bed rest modifies sympathetic neural recruitment strategies in male and female participants.

To understand the impact of physical deconditioning with head-down tilt bed rest (HDBR) on the malleability of sympathetic discharge patterns, we studied 1) baseline integrated muscle sympathetic nerve activity (MSNA; microneurography) from 13 female participants in the WISE-2005 60-day HDBR study (retrospective analysis), 2) integrated MSNA and multiunit action potential (AP) analysis in 13 male participants performed on data collected at baseline and during physiological stress imposed by end-inspiratory apnea in a new 60-day HDBR study, and 3) a repeatability study (control; n = 6, retrospective analysis, 4 wk between tests). Neither baseline integrated burst frequency nor incidence were altered with HDBR (both P > 0.35). However, baseline integrated burst latency increased in both HDBR studies (male: 1.35 ± 0.02 to 1.39 ± 0.02 s, P < 0.01; female: 1.23 ± 0.02 to 1.29 ± 0.02 s, P < 0.01), whereas controls exhibited no change across two visits (1.25 ± 0.02 to 1.25 ± 0.02 s, group-by-time interaction, P = 0.02). With the exception of increased AP latency ( P = 0.03), male baseline AP data did not change with HDBR (all P > 0.19). The change in AP frequency on going from baseline to apnea (∆94 ± 25 to ∆317 ± 55 AP/min, P < 0.01) and the number of active sympathetic clusters per burst (∆0 ± 0.2 to ∆1 ± 0.2 clusters/burst, P = 0.02) were greater post- compared with pre-HDBR. The change in total clusters with apnea was ∆0 ± 0.5 clusters pre- and ∆2 ± 0.7 clusters post-HDBR ( P = 0.07). These data indicate that 60-day HDBR modified discharge characteristics in baseline burst latency and sympathetic neural recruitment during apneic stress. NEW & NOTEWORTHY Long-duration bed rest did not modify baseline sympathetic burst frequency in male and female participants, but examination of additional features of the multiunit signal provided novel evidence to suggest augmented synaptic delays or processing times at baseline for all sympathetic action potentials. Furthermore, long-duration bed rest increased reflex-sympathetic arousal to apneic stress in male participants primarily by mechanisms involving an augmented firing rate of action potential clusters active at baseline.

Multi-System Deconditioning in 3-Day Dry Immersion without Daily Raise.

Dry immersion (DI) is a Russian-developed, ground-based model to study the physiological effects of microgravity. It accurately reproduces environmental conditions of weightlessness, such as enhanced physical inactivity, suppression of hydrostatic pressure and supportlessness. We aimed to study the integrative physiological responses to a 3-day strict DI protocol in 12 healthy men, and to assess the extent of multi-system deconditioning. We recorded general clinical data, biological data and evaluated body fluid changes. Cardiovascular deconditioning was evaluated using orthostatic tolerance tests (Lower Body Negative Pressure + tilt and progressive tilt). Metabolic state was tested with oral glucose tolerance test. Muscular deconditioning was assessed via muscle tone measurement. Results: Orthostatic tolerance time dropped from 27 ± 1 to 9 ± 2 min after DI. Significant impairment in glucose tolerance was observed. Net insulin response increased by 72 ± 23% on the third day of DI compared to baseline. Global leg muscle tone was approximately 10% reduced under immersion. Day-night changes in temperature, heart rate and blood pressure were preserved on the third day of DI. Day-night variations of urinary K+ diminished, beginning at the second day of immersion, while 24-h K+ excretion remained stable throughout. Urinary cortisol and melatonin metabolite increased with DI, although within normal limits. A positive correlation was observed between lumbar pain intensity, estimated on the second day of DI, and mean 24-h urinary cortisol under DI. In conclusion, DI represents an accurate and rapid model of gravitational deconditioning. The extent of glucose tolerance impairment may be linked to constant enhanced muscle inactivity. Muscle tone reduction may reflect the reaction of postural muscles to withdrawal of support. Relatively modest increases in cortisol suggest that DI induces a moderate stress effect. In prospect, this advanced ground-based model is extremely suited to test countermeasures for microgravity-induced deconditioning and physical inactivity-related pathologies.

Internal carotid, external carotid and vertebral artery blood flow responses to 3 days of head-out dry immersion.

NEW FINDINGS: What is the central question of this study? The extent to which weightlessness associated with a fluid shift from the peripheral to the central circulation influences the blood flow in each cerebral artery remains unknown. The present study was designed to explore the effect of short-term weightlessness conditions on both anterior and posterior cerebral blood flow. What is the main finding and its importance? Short-term weightlessness affects both anterior and posterior cerebral vasculature. However, a heterogeneous cerebral blood flow response in each cerebral artery did not occur during 3 days of dry immersion. We have recently demonstrated that a heterogeneous cerebral blood flow (CBF) response in each cerebral artery might contribute to the maintenance of circulatory homeostasis in the brain. However, the extent to which weightlessness associated with a fluid shift from the peripheral to the central circulation influences the distribution of CBF in each cerebral artery remains unknown. We hypothesized that a dry immersion-induced fluid shift (weightlessness conditions) would cause a heterogeneous CBF response in each cerebral artery. During and after 3 days of dry immersion, the blood flows in the internal carotid (ICA), external carotid (ECA) and vertebral arteries (VA) were measured by Doppler ultrasonography using an 8 MHz linear transducer. Although the 3 days of dry immersion and the 2 days recovery period did not change the blood flow in each cerebral artery, the conductance in both ICA and VA decreased during dry immersion on days 2 and 3 (ICA, 2.95 and 3.23 ml min-1  mmHg-1 ; VA, 1.10 and 1.05 ml min-1  mmHg-1 , respectively) from the baseline (ICA, 3.47 ml min-1  mmHg-1 , P = 0.027; VA, 1.23 ml min-1  mmHg-1 , P = 0.004). In addition, Pearson correlation analysis demonstrated that the 3 days of dry immersion induced a decrease in cardiac output (P = 0.004) that was associated with changes in ICA (P = 0.046) and VA blood flow (P = 0.021), but not ECA blood flow (P = 0.466). These findings suggest that short exposures to weightlessness, acting via a cephalad redistribution of fluid volume and blood flow in the human body, influenced the cerebral vasculature in each cerebral artery but did not cause a heterogeneous CBF response in each cerebral artery.