A brain-spinal interface (BSI) system-on-chip (SoC) for closed-loop cortically-controlled intraspinal microstimulation

This paper reports on a fully miniaturized brain-spinal interface system for closed-loop cortically-controlled intraspinal microstimulation (ISMS). Fabricated in AMS 0.35 µm two-poly four-metal complementary metal–oxide–semiconductor technology, this system-on-chip measures ~ 3.46 mm × 3.46 mm and incorporates two identical 4-channel modules, each comprising a spike-recording front-end, embedded digital signal processing (DSP) unit, and programmable stimulating back-end. The DSP unit is capable of generating multichannel trigger signals for a wide array of ISMS triggering patterns based on real-time discrimination of a programmable number of intracortical neural spikes within a pre-specified time-bin duration via thresholding and user-adjustable time–amplitude windowing. The system is validated experimentally using an anesthetized rat model of a spinal cord contusion injury at the T8 level. Multichannel neural spikes are recorded from the cerebral cortex and converted in real time into electrical stimuli delivered to the lumbar spinal cord below the level of the injury, resulting in distinct patterns of hindlimb muscle activation

LES-based Study of the Roughness Effects on the Wake of a Circular Cylinder from Subcritical to Transcritical Reynolds Numbers

This paper investigates the effects of surface roughness on the flow past a circular cylinder at subcritical to transcritical Reynolds numbers. Large eddy simulations of the flow for sand grain roughness of size k/D = 0.02 are performed (D is the cylinder diameter). Results show that surface roughness triggers the transition to turbulence in the boundary layer at all Reynolds numbers, thus leading to an early separation caused by the increased momentum deficit, especially at transcritical Reynolds numbers. Even at subcritical Reynolds numbers, boundary layer instabilities are triggered in the roughness sublayer and eventually lead to the transition to turbulence. The early separation at transcritical Reynolds numbers leads to a wake topology similar to that of the subcritical regime, resulting in an increased drag coefficient and lower Strouhal number. Turbulent statistics in the wake are also affected by roughness; the Reynolds stresses are larger due to the increased turbulent kinetic energy production in the boundary layer and separated shear layers close to the cylinder shoulders.We acknowledge “Red Española de Surpercomputación” (RES) for awarding us access to the MareNostrum III machine based in Barcelona, Spain (Ref. FI-2015-2-0026 and FI-2015-3-0011). We also acknowledge PRACE for awarding us access to Fermi and Marconi Supercomputers at Cineca, Italy (Ref. 2015133120). Oriol Lehmkuhl acknowledges a PDJ 2014 Grant by AGAUR (Generalitat de Catalunya). Ugo Piomelli acknowledges the support of the Natural Sciences and Engineering Research Council (NSERC) of Canada under the Discovery Grant Programme (Grant No. RGPIN-2016-04391). Ricard Borrell acknowledges a Juan de la Cierva postdoctoral grant (IJCI-2014-21034). Ivette Rodriguez, Oriol Lehmkuhl, Ricard Borrell and Assensi Oliva acknowledge Ministerio de Economía y Competitividad, Secretaría de Estado de Investigación, Desarrollo e Innovación, Spain (ref. ENE2014-60577-R).Peer ReviewedPostprint (author's final draft

Ventilation inhibits sympathetic action potential recruitment even during severe chemoreflex stress

© 2017 the American Physiological Society. This study investigated the influence of ventilation on sympathetic action potential (AP) discharge patterns during varying levels of high chemoreflex stress. In seven trained breath-hold divers (age 33 ± 12 yr), we measured muscle sympathetic nerve activity (MSNA) at baseline, during preparatory rebreathing (RBR), and during 1) functional residual capacity apnea (FRCApnea) and 2) continued RBR. Data from RBR were analyzed at matched (i.e., to FRCApnea) hemoglobin saturation (HbSat) levels (RBRMatched) or more severe levels (RBREnd). A third protocol compared alternating periods (30 s) of FRC and RBR (FRC-RBRALT). Subjects continued each protocol until 85% volitional tolerance. AP patterns in MSNA (i.e., providing the true neural content of each sympathetic burst) were studied using wavelet-based methodology. First, for similar levels of chemoreflex stress (both HbSat: 71 ± 6%; P = NS), RBRMatched was associated with reduced AP frequency and APs per burst compared with FRCApnea (both P _ 0.001). When APs were binned according to peak-to-peak amplitude (i.e., into clusters), total AP clusters increased during FRCApnea (+10 ± 2; P \u3c 0.001) but not during RBRMatched (+1 ± 2; P = NS). Second, despite more severe chemoreflex stress during RBREnd (Hb-Sat: 56 ± 13 vs. 71 ± 6%; P = 0.001), RBREnd was associated with a restrained increase in the APs per burst (FRCApnea: +18 ± 7; RBREnd: +11 ± 5) and total AP clusters (FRCApnea: +10 ± 2; RBREnd: +6 ± 4) (both P \u3c 0.01). During FRC-RBRALT, all periods of FRC elicited sympathetic AP recruitment (all P \u3c 0.001), whereas all periods of RBR were associated with complete withdrawal of AP recruitment (all P = NS). Presently, we demonstrate that ventilation per se restrains and/or inhibits sympathetic axonal recruitment during high, and even extreme, chemoreflex stress. NEW & NOTEWORTHY The current study demonstrates that the sympathetic neural recruitment patterns observed during chemoreflex activation induced by rebreathing or apnea are restrained and/or inhibited by the act of ventilation per se, despite similar, or even greater, levels of severe chemoreflex stress. Therefore, ventilation modulates not only the timing of sympathetic bursts but also the within-burst axonal recruitment normally observed during progressive chemoreflex stress

Effects of 6 Months of Exercise-Based Cardiac Rehabilitation on Autonomic Function and Neuro-Cardiovascular Stress Reactivity in Coronary Artery Disease Patients

Background Autonomic dysregulation represents a hallmark of coronary artery disease (CAD). Therefore, we investigated the effects of exercise-based cardiac rehabilitation (CR) on autonomic function and neuro-cardiovascular stress reactivity in CAD patients. Methods and Results Twenty-two CAD patients (4 women; 62±8 years) were studied before and following 6 months of aerobic- and resistance-training-based CR. Twenty-two similarly aged, healthy individuals (CTRL; 7 women; 62±11 years) served as controls. We measured blood pressure, muscle sympathetic nerve activity, heart rate, heart rate variability (linear and nonlinear), and cardiovagal (sequence method) and sympathetic (linear relationship between burst incidence and diastolic blood pressure) baroreflex sensitivity during supine rest. Furthermore, neuro-cardiovascular reactivity during short-duration static handgrip (20s) at 40% maximal effort was evaluated. Six months of CR lowered resting blood pressure (P\u3c0.05), as well as muscle sympathetic nerve activity burst frequency (48±8 to 39±11 bursts/min; P\u3c0.001) and burst incidence (81±7 to 66±17 bursts/100 heartbeats; P\u3c0.001), to levels that matched CTRL and improved sympathetic baroreflex sensitivity in CAD patients (P\u3c0.01). Heart rate variability (all P\u3e0.05) and cardiovagal baroreflex sensitivity (P=0.11) were unchanged following CR, yet values were not different pre-CR from CTRL (all P\u3e0.05). Furthermore, before CR, CAD patients displayed greater blood pressure and muscle sympathetic nerve activity reactivity to static handgrip versus CTRL (all P\u3c0.05); yet, responses were reduced following CR (all P\u3c0.05) to levels observed in CTRL. Conclusions Six months of exercise-based CR was associated with marked improvement in baseline autonomic function and neuro-cardiovascular stress reactivity in CAD patients, which may play a role in the reduced cardiac risk and improved survival observed in patients following exercise training

Classifying Alzheimer's disease and frontotemporal dementia using machine learning with cross-sectional and longitudinal magnetic resonance imaging data

Alzheimer's disease (AD) and frontotemporal dementia (FTD) are common causes of dementia with partly overlapping, symptoms and brain signatures. There is a need to establish an accurate diagnosis and to obtain markers for disease tracking. We combined unsupervised and supervised machine learning to discriminate between AD and FTD using brain magnetic resonance imaging (MRI). We included baseline 3T-T1 MRI data from 339 subjects: 99 healthy controls (CTR), 153 AD and 87 FTD patients; and 2-year follow-up data from 114 subjects. We obtained subcortical gray matter volumes and cortical thickness measures using FreeSurfer. We used dimensionality reduction to obtain a single feature that was later used in a support vector machine for classification. Discrimination patterns were obtained with the contribution of each region to the single feature. Our algorithm differentiated CTR versus AD and CTR versus FTD at the cross-sectional level with 83.3% and 82.1% of accuracy. These increased up to 90.0% and 88.0% with longitudinal data. When we studied the classification between AD versus FTD we obtained an accuracy of 63.3% at the cross-sectional level and 75.0% for longitudinal data. The AD versus FTD versus CTR classification has reached an accuracy of 60.7%, and 71.3% for cross-sectional and longitudinal data respectively. Disease discrimination brain maps are in concordance with previous results obtained with classical approaches. By using a single feature, we were capable to classify CTR, AD, and FTD with good accuracy, considering the inherent overlap between diseases. Importantly, the algorithm can be used with cross-sectional and longitudinal data.© 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC

Treballs d'investigació en atenció primària: revisió dels treballs en llengües espanyoles publicats l'any 1986

Revisem 29 treballs elaborats per professionals d'atenció primària i publicats a: Atención Primaria, Medicina Clínica, Gaseta Sanitaria, Revista Clínica Española, Revista Española de Pediatría i Annals de Medicina. La majoria els trobem realitzats per especialistes o residents de Medicina Familiar i Comunitària, amb absència de pediatres. Entre els temes analitzats destaca l'anàlisi de la demanda, hipertensió arterial i vacunacions, que totalitzen quasi el 50% dels treballs. Cal ressaltar un 89% de dissenys descriptius, amb solament dos de tipus analític o experimental. Sobre 6 paràmetres d'adequació metodològica hi hagué un compliment mitjà de 4,38 (DE = 2,23). El 52% dels treballs no tenien tractament estadístic. Creiem que hi ha una extensa variabilitat en la qualitat deis treballs i que és necessari adaptar la temàtica d'interès deis investigadors i adaptar els dissenys a la demostració d'hipòtesis que suposin canvis en la pràctica assistencial

Inequalities in mortality of men by oral and pharyngeal cancer in Barcelona, Spain and São Paulo, Brazil, 1995–2003

<p>Abstract</p> <p>Background</p> <p>Large inequalities of mortality by most cancers in general, by mouth and pharynx cancer in particular, have been associated to behaviour and geopolitical factors. The assessment of socioeconomic covariates of cancer mortality may be relevant to a full comprehension of distal determinants of the disease, and to appraise opportune interventions. The objective of this study was to compare socioeconomic inequalities in male mortality by oral and pharyngeal cancer in two major cities of Europe and South America.</p> <p>Methods</p> <p>The official system of information on mortality provided data on deaths in each city; general censuses informed population data. Age-adjusted death rates by oral and pharyngeal cancer for men were independently assessed for neighbourhoods of Barcelona, Spain, and São Paulo, Brazil, from 1995 to 2003. Uniform methodological criteria instructed the comparative assessment of magnitude, trends and spatial distribution of mortality. General linear models assessed ecologic correlations between death rates and socioeconomic indices (unemployment, schooling levels and the human development index) at the inner-city area level. Results obtained for each city were subsequently compared.</p> <p>Results</p> <p>Mortality of men by oral and pharyngeal cancer ranked higher in Barcelona (9.45 yearly deaths per 100,000 male inhabitants) than in Spain and Europe as a whole; rates were on decrease. São Paulo presented a poorer profile, with higher magnitude (11.86) and stationary trend. The appraisal of ecologic correlations indicated an unequal and inequitably distributed burden of disease in both cities, with poorer areas tending to present higher mortality. Barcelona had a larger gradient of mortality than São Paulo, indicating a higher inequality of cancer deaths across its neighbourhoods.</p> <p>Conclusion</p> <p>The quantitative monitoring of inequalities in health may contribute to the formulation of redistributive policies aimed at the concurrent promotion of wellbeing and social justice. The assessment of groups experiencing a higher burden of disease can instruct health services to provide additional resources for expanding preventive actions and facilities aimed at early diagnosis, standardized treatments and rehabilitation.</p

The climatic challenge: which plants will people use in the next century?

More than 31,000 useful plant species have been documented to fulfil needs and services for humans or the animals and environment we depend on. Despite this diversity, humans currently satisfy most requirements with surprisingly few plant species; for example, just three crops – rice, wheat and maize – comprise more than 50% of plant derived calories. Here, we synthesize the projected impact of global climatic change on useful plants across the spectrum of plant domestication. We illustrate the demographic, spatial, ecophysiological, chemical, functional, evolutionary and cultural traits that are likely to characterise useful plants and their resilience in the next century. Using this framework, we consider a range of possible pathways for future human use of plants. These are centred on two trade-offs: i) diversification versus specialization in the range of species we utilize, and ii) substitutionof the species towards those better suited to future climate versus facilitating adaptation in our existing suite of dominant useful plants. In the coming century, major challenges to agriculture and biodiversity will be dominated by increased climatic variation, shifting species ranges, disruption to biotic interactions, nutrient limitation and emerging pests and pathogens. These challenges must be mitigated, whilst enhancing sustainable production to meet the needs of a growing population and a more resource intensive standard of living. With the continued erosion of biodiversity, our future ability to choose among these pathways and trade-offs is likely to be diminished

Socioeconomic inequalities in suicide mortality in European urban areas before and during the economic recession

Few studies have assessed the impact of the financial crisis on inequalities in suicide mortality in European urban areas. The objective of the study was to analyse the trend in area socioeconomic inequalities in suicide mortality in nine European urban areas before and after the beginning of the financial crisis. This ecological study of trends was based on three periods, two before the economic crisis (2000-2003, 2004-2008) and one during the crisis (2009-2014). The units of analysis were the small areas of nine European cities or metropolitan areas, with a median population ranging from 271 (Turin) to 193 630 (Berlin). For each small area and sex, we analysed smoothed standardized mortality ratios of suicide mortality and their relationship with a socioeconomic deprivation index using a hierarchical Bayesian model. Among men, the relative risk (RR) comparing suicide mortality of the 95th percentile value of socioeconomic deprivation (severe deprivation) to its 5th percentile value (low deprivation) were higher than 1 in Stockholm and Lisbon in the three periods. In Barcelona, the RR was 2.06 (95% credible interval: 1.24-3.21) in the first period, decreasing in the other periods. No significant changes were observed across the periods. Among women, a positive significant association was identified only in Stockholm (RR around 2 in the three periods). There were no significant changes across the periods except in London with a RR of 0.49 (95% CI: 0.35-0.68) in the third period. Area socioeconomic inequalities in suicide mortality did not change significantly after the onset of the crisis in the areas studied