Impacts of the Tropical Pacific/Indian Oceans on the Seasonal Cycle of the West African Monsoon

The current consensus is that drought has developed in the Sahel during the second half of the twentieth century as a result of remote effects of oceanic anomalies amplified by local land–atmosphere interactions. This paper focuses on the impacts of oceanic anomalies upon West African climate and specifically aims to identify those from SST anomalies in the Pacific/Indian Oceans during spring and summer seasons, when they were significant. Idealized sensitivity experiments are performed with four atmospheric general circulation models (AGCMs). The prescribed SST patterns used in the AGCMs are based on the leading mode of covariability between SST anomalies over the Pacific/Indian Oceans and summer rainfall over West Africa. The results show that such oceanic anomalies in the Pacific/Indian Ocean lead to a northward shift of an anomalous dry belt from the Gulf of Guinea to the Sahel as the season advances. In the Sahel, the magnitude of rainfall anomalies is comparable to that obtained by other authors using SST anomalies confined to the proximity of the Atlantic Ocean. The mechanism connecting the Pacific/Indian SST anomalies with West African rainfall has a strong seasonal cycle. In spring (May and June), anomalous subsidence develops over both the Maritime Continent and the equatorial Atlantic in response to the enhanced equatorial heating. Precipitation increases over continental West Africa in association with stronger zonal convergence of moisture. In addition, precipitation decreases over the Gulf of Guinea. During the monsoon peak (July and August), the SST anomalies move westward over the equatorial Pacific and the two regions where subsidence occurred earlier in the seasons merge over West Africa. The monsoon weakens and rainfall decreases over the Sahel, especially in August.Peer reviewe

Study of W boson production in pPb collisions at vsNN = 5.02 TeV

The first study of W boson production in pPb collisions is presented, for bosons decaying to a muon or electron, and a neutrino. The measurements are based on a data sample corresponding to an integrated luminosity of 34.6 nb-1 at a nucleon–nucleon centre-of-mass energy of vsNN = 5.02 TeV, collected by the CMS experiment. The W boson differential cross sections, lepton charge asymmetry, and forward–backward asymmetries are measured for leptons of transverse momentum exceeding 25 GeV/c, and as a function of the lepton pseudorapidity in the |?lab| < 2.4range. Deviations from the expectations based on currently available parton distribution functions are observed, showing the need for including W boson data in nuclear parton distribution global fits

High-resolution microdialysis applied to the study and treatment of brain metabolic disorders

En las últimas dos décadas, tanto médicos como los investigadores han considerado la hipoxia cerebral isquémica y no isquémica, como la protagonista de la mayoría de las lesiones secundarias que ocurren en pacientes con un traumatismo craneoencefálico (TCE) grave. Tanto la lesión primaria como la isquemia cerebral desencadenan la liberación de neurotransmisores y un fallo energético que provoca flujos iónicos masivos, con el posterior movimiento osmótico del agua a través de las células seguido de edema cerebral. El edema cerebral es la principal causa de muerte y discapacidad en estos pacientes. Una mejor comprensión de los complejos trastornos iónicos que causan el edema beneficiaría el estudio y el tratamiento no sólo de los pacientes con un TCE, sino también de los pacientes con otras lesiones neurológicas agudas, como el infarto maligno de la arteria cerebral media (IMACM). La hiperoxia normobárica (HN) es una estrategia ya testada en modelos experimentales de TCE y en ensayos clínicos piloto. La potencial toxicidad de usar niveles supra-normales de O2 es la principal preocupación de utilizar esta terapia. Una FiO2 alta puede inducir vasoconstricción, exacerbar el estrés oxidativo (EO), aumentar la neuroinflamación, o inducir excitotoxicidad. Las técnicas actuales de neuromonitorización multimodal (NMM) permiten el estudio de los procesos que ocurren tras una lesión cerebral aguda. La microdiálisis cerebral (MD) es una técnica avanzada de NMM que permite el muestreo continuo del parénquima cerebral. Los objetivos principales de esta tesis fueron: 1) determinar el perfil iónico del espacio extracelular cerebral (ECC) en diferentes áreas del cerebro en pacientes con una lesión cerebral aguda, 2) evaluar la respuesta metabólica de pacientes con un TCE a la HN y determinar si la hiperoxia aumenta el EO y 3) reproducir in vitro los perfiles metabólicos cerebrales en la hipoxia de baja extractividad (HBE). En primer lugar, para analizar el perfil iónico de ECC se analizaron muestras de microdiálisis de 34 pacientes (TBI y IMACM) según la localización del catéter MD, mediante espectrometría de masas con plasma acoplado inductivamente (ICP-MS). Los resultados mostraron que la composición iónica del ECC cerebral difiere según la gravedad de la alteración tisular. Por lo tanto, los resultados deben interpretarse de acuerdo con la región del cerebro muestreada por el catéter de MD. La ICP-MS acoplada a los ensayos iónicos es una poderosa herramienta para una mejor comprensión de los complejos trastornos iónicos que se producen como consecuencia de estas lesiones. En segundo lugar, para evaluar la respuesta metabólica del cerebro lesionado a la HN y determinar si la hiperoxia aumenta el EO, se estudió el perfil metabólico y se determinó la presencia de EO usando un robusto indicador (8-iso-PGF2α), en 34 pacientes con un TCE. La NH incrementó los valores de PtiO2 tanto en el cerebro lesionado macroscópicamente normal como en regiones traumáticas en riesgo. Los resultados metabólicos sugirieron que los pacientes que muestran indicios de un metabolismo cerebral alterado podrían beneficiarse de recibir esta terapia. La HN provocó un incremento del EO, solo en aquellos pacientes que presentaban niveles basales de EO. Combinado con la creciente evidencia de que las crisis metabólicas son comunes en el TCE sin isquemia cerebral, estos hallazgos abren nuevas vías para el uso de esta estrategia terapéutica en pacientes con TCE. Finalmente, utilizando un modelo in vitro de astrocitos corticales humanos se determinó el perfil metabólico y los cambios en la maquinaria glicolítica de la LEH. Este es un primer paso para explorar las consecuencias de la HBE que permite profundizar en el conocimiento de formas más complejas de la hipoxia cerebral descritas en lesiones cerebrales agudas.In the past two decades, both clinicians and researchers have considered brain ischemic and non-ischemic cerebral hypoxia, the protagonist of most secondary lesions occurring in patients with severe traumatic brain injury (TBI). Both primary damage and cerebral ischemia trigger the release of neurotransmitters and an energy failure that causes massive ionic fluxes. Subsequent osmotic water movement across the cells is followed by brain edema. Brain edema is the major leading cause of death and disability in these patients. Better understanding of the complex ionic disturbances that cause edema would benefit the study and treatment of not only TBI patients but also patients with other acute neurological injuries, such as malignant middle cerebral artery infarct (MMCAI). Normobaric brain oxygen therapy (NBO) is one strategy already tested in experimental models of TBI and in pilot clinical trials. The main concern regarding NBO is the potential toxicity of using supranormal levels of partial pressure of arterial oxygen. High FiO2 could induce vasoconstriction, exacerbate oxidative stress (OxS), increase neuroinflammation, or induce excitotoxicity. Current multimodal neuromonitoring (MNM) techniques allow the study of the processes occurring after acute brain injury. Cerebral microdialysis (MD) is an advanced MNM technique that allows continuous sampling of the cerebral parenchyma. The main objectives of this thesis were: 1) to determine the ionic profile of brain extracellular space (ECS) in different brain areas in patients with acute brain injury, 2) to evaluate the metabolic response of TBI patients to 4 h of NBO and to determine whether hyperoxia increases OxS, and 3) to reproduce in vitro the abnormal brain metabolic profiles in one of the types of hypoxia described by Siggaar-Andersen in 1995 (low-extractivity hypoxia -LEH-). First, to analyze the ionic profile of brain ECS, microdialysate samples of 34 patients (TBI and MMCAI) were analyzed using inductively coupled plasma mass spectrometry (ICP-MS). The ionic profile was studied according to the position of the MD catheter. The results showed that the ionic composition of the brain ECS differs according to the severity of the tissue disturbance. Thus, the results should be interpreted according to the region of the brain sampled by the MD catheter. ICP-MS coupled to ionic assays creates a powerful tool for a better understanding of the complex ionic disturbances that occur after acute brain lesions. Secondly, 34 TBI patients were included to assess the metabolic response of the injured brain to NBO and to determine whether hyperoxia increases OxS. The results showed that NBO increased PtiO2 in both macroscopically normal injured brain and in traumatic regions at risk. NBO did not change energy metabolism in the entire group of patients. These results suggest that TBI patients would benefit from receiving NBO when they show indications of disturbed brain metabolism. The presence of OxS in MD samples was additionally measured using a robust indicator (8-iso-PGF2α). NBO maintained for 4 h did not induce OxS in patients without pre-existing OxS at baseline. However, for patients in whom OxS was detected at baseline, NBO induced a significant increase in 8-iso-PGF2α. Combined with the increasing evidence that metabolic crises are common in TBI without brain ischemia, these findings open new avenues for the use of this accessible therapeutic strategy in TBI patients. Finally, using an in vitro model of human cortical astrocytes, the energy metabolic profile and the changes in the glycolytic machinery of LEH were reproduced. This is a first step toward exploring the consequences of LEH in vitro for a better understating of the MD pattern found in neurocritical patients. Our aim was to acquire in-depth knowledge of more complex forms of brain hypoxia found in acute brain injuries

High-resolution microdialysis applied to the study and treatment of brain metabolic disorders

Premi Extraordinari de Doctorat concedit pels programes de doctorat de la UAB per curs acadèmic 2016-2017En las últimas dos décadas, tanto médicos como los investigadores han considerado la hipoxia cerebral isquémica y no isquémica, como la protagonista de la mayoría de las lesiones secundarias que ocurren en pacientes con un traumatismo craneoencefálico (TCE) grave. Tanto la lesión primaria como la isquemia cerebral desencadenan la liberación de neurotransmisores y un fallo energético que provoca flujos iónicos masivos, con el posterior movimiento osmótico del agua a través de las células seguido de edema cerebral. El edema cerebral es la principal causa de muerte y discapacidad en estos pacientes. Una mejor comprensión de los complejos trastornos iónicos que causan el edema beneficiaría el estudio y el tratamiento no sólo de los pacientes con un TCE, sino también de los pacientes con otras lesiones neurológicas agudas, como el infarto maligno de la arteria cerebral media (IMACM). La hiperoxia normobárica (HN) es una estrategia ya testada en modelos experimentales de TCE y en ensayos clínicos piloto. La potencial toxicidad de usar niveles supra-normales de O2 es la principal preocupación de utilizar esta terapia. Una FiO2 alta puede inducir vasoconstricción, exacerbar el estrés oxidativo (EO), aumentar la neuroinflamación, o inducir excitotoxicidad. Las técnicas actuales de neuromonitorización multimodal (N12) permiten el estudio de los procesos que ocurren tras una lesión cerebral aguda. La microdiálisis cerebral (MD) es una técnica avanzada de N12 que permite el muestreo continuo del parénquima cerebral. Los objetivos principales de esta tesis fueron: 1) determinar el perfil iónico del espacio extracelular cerebral (ECC) en diferentes áreas del cerebro en pacientes con una lesión cerebral aguda, 2) evaluar la respuesta metabólica de pacientes con un TCE a la HN y determinar si la hiperoxia aumenta el EO y 3) reproducir in vitro los perfiles metabólicos cerebrales en la hipoxia de baja extractividad (HBE). En primer lugar, para analizar el perfil iónico de ECC se analizaron muestras de microdiálisis de 34 pacientes (TBI y IMACM) según la localización del catéter MD, mediante espectrometría de masas con plasma acoplado inductivamente (ICP-MS). Los resultados mostraron que la composición iónica del ECC cerebral difiere según la gravedad de la alteración tisular. Por lo tanto, los resultados deben interpretarse de acuerdo con la región del cerebro muestreada por el catéter de MD. La ICP-MS acoplada a los ensayos iónicos es una poderosa herramienta para una mejor comprensión de los complejos trastornos iónicos que se producen como consecuencia de estas lesiones. En segundo lugar, para evaluar la respuesta metabólica del cerebro lesionado a la HN y determinar si la hiperoxia aumenta el EO, se estudió el perfil metabólico y se determinó la presencia de EO usando un robusto indicador (8-iso-PGF2α), en 34 pacientes con un TCE. La NH incrementó los valores de PtiO2 tanto en el cerebro lesionado macroscópicamente normal como en regiones traumáticas en riesgo. Los resultados metabólicos sugirieron que los pacientes que muestran indicios de un metabolismo cerebral alterado podrían beneficiarse de recibir esta terapia. La HN provocó un incremento del EO, solo en aquellos pacientes que presentaban niveles basales de EO. Combinado con la creciente evidencia de que las crisis metabólicas son comunes en el TCE sin isquemia cerebral, estos hallazgos abren nuevas vías para el uso de esta estrategia terapéutica en pacientes con TCE. Finalmente, utilizando un modelo in vitro de astrocitos corticales humanos se determinó el perfil metabólico y los cambios en la maquinaria glicolítica de la LEH. Este es un primer paso para explorar las consecuencias de la HBE que permite profundizar en el conocimiento de formas más complejas de la hipoxia cerebral descritas en lesiones cerebrales agudas.In the past two decades, both clinicians and researchers have considered brain ischemic and non-ischemic cerebral hypoxia, the protagonist of most secondary lesions occurring in patients with severe traumatic brain injury (TBI). Both primary damage and cerebral ischemia trigger the release of neurotransmitters and an energy failure that causes massive ionic fluxes. Subsequent osmotic water movement across the cells is followed by brain edema. Brain edema is the major leading cause of death and disability in these patients. Better understanding of the complex ionic disturbances that cause edema would benefit the study and treatment of not only TBI patients but also patients with other acute neurological injuries, such as malignant middle cerebral artery infarct (MMCAI). Normobaric brain oxygen therapy (NBO) is one strategy already tested in experimental models of TBI and in pilot clinical trials. The main concern regarding NBO is the potential toxicity of using supranormal levels of partial pressure of arterial oxygen. High FiO2 could induce vasoconstriction, exacerbate oxidative stress (OxS), increase neuroinflammation, or induce excitotoxicity. Current multimodal neuromonitoring (MNM) techniques allow the study of the processes occurring after acute brain injury. Cerebral microdialysis (MD) is an advanced MNM technique that allows continuous sampling of the cerebral parenchyma. The main objectives of this thesis were: 1) to determine the ionic profile of brain extracellular space (ECS) in different brain areas in patients with acute brain injury, 2) to evaluate the metabolic response of TBI patients to 4 h of NBO and to determine whether hyperoxia increases OxS, and 3) to reproduce in vitro the abnormal brain metabolic profiles in one of the types of hypoxia described by Siggaar-Andersen in 1995 (low-extractivity hypoxia -LEH-). First, to analyze the ionic profile of brain ECS, microdialysate samples of 34 patients (TBI and MMCAI) were analyzed using inductively coupled plasma mass spectrometry (ICP-MS). The ionic profile was studied according to the position of the MD catheter. The results showed that the ionic composition of the brain ECS differs according to the severity of the tissue disturbance. Thus, the results should be interpreted according to the region of the brain sampled by the MD catheter. ICP-MS coupled to ionic assays creates a powerful tool for a better understanding of the complex ionic disturbances that occur after acute brain lesions. Secondly, 34 TBI patients were included to assess the metabolic response of the injured brain to NBO and to determine whether hyperoxia increases OxS. The results showed that NBO increased PtiO2 in both macroscopically normal injured brain and in traumatic regions at risk. NBO did not change energy metabolism in the entire group of patients. These results suggest that TBI patients would benefit from receiving NBO when they show indications of disturbed brain metabolism. The presence of OxS in MD samples was additionally measured using a robust indicator (8-iso-PGF2α). NBO maintained for 4 h did not induce OxS in patients without pre-existing OxS at baseline. However, for patients in whom OxS was detected at baseline, NBO induced a significant increase in 8-iso-PGF2α. Combined with the increasing evidence that metabolic crises are common in TBI without brain ischemia, these findings open new avenues for the use of this accessible therapeutic strategy in TBI patients. Finally, using an in vitro model of human cortical astrocytes, the energy metabolic profile and the changes in the glycolytic machinery of LEH were reproduced. This is a first step toward exploring the consequences of LEH in vitro for a better understating of the MD pattern found in neurocritical patients. Our aim was to acquire in-depth knowledge of more complex forms of brain hypoxia found in acute brain injuries

Lactate and the lactate-to-pyruvate molar ratio cannot be used as independent biomarkers for monitoring brain energetic metabolism: a microdialysis study in patients with traumatic brain injuries.

BACKGROUND: For decades, lactate has been considered an excellent biomarker for oxygen limitation and therefore of organ ischemia. The aim of the present study was to evaluate the frequency of increased brain lactate levels and the LP ratio (LPR) in a cohort of patients with severe or moderate traumatic brain injury (TBI) subjected to brain microdialysis monitoring to analyze the agreement between these two biomarkers and to indicate brain energy metabolism dysfunction. METHODS: Forty-six patients with an admission Glasgow coma scale score of ≤13 after resuscitation admitted to a dedicated 10-bed Neurotraumatology Intensive Care Unit were included, and 5305 verified samples of good microdialysis data were analyzed. RESULTS: Lactate levels were above 2.5 mmol/L in 56.9% of the samples. The relationships between lactate and the LPR could not be adequately modeled by any linear or non-linear model. Neither Cohen's kappa nor Gwet's statistic showed an acceptable agreement between both biomarkers to classify the samples in regard to normal or abnormal metabolism. The dataset was divided into four patterns defined by the lactate concentrations and the LPR. A potential interpretation for these patterns is suggested and discussed. Pattern 4 (low pyruvate levels) was found in 10.7% of the samples and was characterized by a significantly low concentration of brain glucose compared with the other groups. CONCLUSIONS: Our study shows that metabolic abnormalities are frequent in the macroscopically normal brain in patients with traumatic brain injuries and a very poor agreement between lactate and the LPR when classifying metabolism. The concentration of lactate in the dialysates must be interpreted while taking into consideration the LPR to distinguish between anaerobic metabolism and aerobic hyperglycolysis

Intermethod agreement in the classification of dialysate samples by lactate and the LPR.

<p>LP, lactate-to-pyruvate; L, lactate; >, greater than; ≤, less than or equal to; N, number of readings; %, percentage.</p

Scatter plot for lactate and the lactate-to-pyruvate ratio.

<p>The entire dataset is divided in the four patterns described in the text. We propose the following terminology for the four patterns: Pattern 1 (normal metabolism), Pattern 2 (aerobic hyperglycolysis), Pattern 3 (anaerobic metabolism), and Pattern 4 (low pyruvate). For an explanation, see the text.</p

Scatter plot of the relationship between lactate and the lactate-to-pyruvate ratio.

<p>The best-fit straight line using an ordinary least squares method is included. In this plot, outliers with a lactate-to-pyruvate ratio >150 were excluded. The plotted residuals and other regression diagnostics show that the relationships between lactate and the lactate-to-pyruvate ratio could not be adequately modeled by any linear or non-linear model.</p