Early warning systems have become an essential tool to mitigate the impact of river floods, whose frequency and magnitude have increased during the last few decades as a consequence of climate ...change. In this context, the Miño River Flood Alert System (MIDAS) early warning system has been developed for the Miño River (Galicia, NW Spain), whose flood events have historically caused severe damage in urban areas and are expected to increase in intensity in the next decades. MIDAS is integrated by a hydrologic (HEC-HMS) and a hydraulic (Iber+) model using precipitation forecast as input data. The system runs automatically and is governed by a set of Python scripts. When any hazard is detected, an alert is issued by the system, including detailed hazards maps, to help decision makers to take precise and effective mitigation measures. Statistical analysis supports the accuracy of hydrologic and hydraulic modules implemented to forecast river flow and flooded critical areas during the analyzed period of time, including some of the most extreme events registered in the Miño River. In fact, MIDAS has proven to be capable of predicting most of the alert situations occurred during the study period, showing its capability to anticipate risk situations.
Cell differentiation involves profound changes in global gene expression that often has to occur in coordination with cell cycle exit. Because cyclin-dependent kinase inhibitor p27 reportedly ...regulates proliferation of neural progenitor cells in the subependymal neurogenic niche of the adult mouse brain, but can also have effects on gene expression, we decided to molecularly analyze its role in adult neurogenesis and oligodendrogenesis. At the cell level, we show that p27 restricts residual cyclin-dependent kinase activity after mitogen withdrawal to antagonize cycling, but it is not essential for cell cycle exit. By integrating genome-wide gene expression and chromatin accessibility data, we find that p27 is coincidentally necessary to repress many genes involved in the transit from multipotentiality to differentiation, including those coding for neural progenitor transcription factors SOX2, OLIG2 and ASCL1. Our data reveal both a direct association of p27 with regulatory sequences in the three genes and an additional hierarchical relationship where p27 repression of
Sox2
leads to reduced levels of its downstream targets
Olig2
and
Ascl1
. In vivo, p27 is also required for the regulation of the proper level of SOX2 necessary for neuroblasts and oligodendroglial progenitor cells to timely exit cell cycle in a lineage-dependent manner.
Coastal marine biodiversity within eastern boundary upwelling systems (EBUS) is closely linked to the cooler sea temperatures associated with them. It has been suggested that global warming could ...lead to enhanced sea surface cooling in EBUS via the intensification of upwelling-favorable winds. Conversely, increased stratification and the widespread warming of the world's oceans could drive these systems in the opposite direction. These competing mechanisms hold the potential for driving the thermal envelopes of EBUS towards – or away from – the thermal envelopes found outside EBUS, with likely contrasting implications for biodiversity conservation in each scenario. Here we characterize the patterns of net sea surface warming rates over more than three decades throughout the global ocean to evaluate if waters inside EBUS are changing differently from those outside EBUS. Results point to a trend of reduced warming inside EBUS, especially along the nearshore. We found that reduced net warming was prevalent in Pacific EBUS but restricted in Atlantic EBUS. In contrast, net warming in the coastal ocean outside EBUS was pervasive and generally associated with proximity to land. Our results suggest that EBUS have been responding to climate change differently from the rest of the global ocean, potentially buffering coastal biomes from decades of global warming.
This paper introduces the neural correlates of phrase rhythm. In short, phrase rhythm is the rhythmic aspect of phrase construction and the relationships between phrases. For the sake of establishing ...the neural correlates, a musical experiment has been designed to induce music-evoked stimuli related to phrase rhythm. Brain activity is monitored through electroencephalography (EEG) by using a brain-computer interface. The power spectral value of each EEG channel is estimated to obtain how power variance distributes as a function of frequency. Our experiment shows statistical differences in
and
bands in the phrase rhythm variations of two classical sonatas, one in bipartite form and the other in rondo form.
There is a dearth of evidence regarding Health-Related Quality of Life (HRQoL) in nonvalvular atrial fibrillation (NVAF) patients undergoing oral anticoagulation therapy. Our objective was to ...describe HRQoL in NVAF patients on oral anticoagulation, focusing on uncontrolled patients on vitamin K antagonists (VKAs) versus controlled patients on VKAs or non-vitamin K antagonist oral anticoagulants (NOACs), in a real-world setting. Additionally, we assessed the clinical characteristics of patients with uncontrolled anticoagulation.
An observational, multicentre, and cross-sectional study, enrolling 38 Spanish Hospitals' Internal Medicine Departments. HRQoL was assessed using the validated Spanish version of the Sawicki questionnaire. High self-perceived HRQoL was indicated by high scores in the general treatment satisfaction and self-efficacy dimensions, and by low scores in the strained social network, daily hassles and distress dimensions.
Five hundred and one patients were included for assessment. Mean scores ± SD were closer to a high perceived HRQoL in controlled than uncontrolled patients for the five dimensions of the questionnaire: 4.9 ± 1.0 versus 3.6 ± 1.3 for general treatment satisfaction; 4.3 ± 1.0 versus 3.6 ± 1.0 for self-efficacy, 3.1 ± 0.9 versus 3.9 ± 1.1 for strained social network, 2.1 ± 0.8 versus 3.0 ± 1.0 for daily hassles and 1.8 ± 0.9 versus 2.6 ± 1.2 for distress.
HRQoL in patients with controlled anticoagulant status treated with NOACs or VKAs was better than in patients with uncontrolled anticoagulant status. This seems to indicate that anticoagulation control status influences perception of HRQoL, highlighting the importance of its evaluation when assessing HRQoL in NVAF patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Background and Aims
Chimeric antigen receptor T cell therapy (CAR-T) has improved the prognosis of patients with refractory hematologic malignancies. The most important toxicities are the ...cytokine release syndrome (CRS), where interleukin 6 (IL-6) plays a major role, and the immune effector cell-associated neurotoxicity syndrome (ICANS). A low incidence of acute kidney injury (AKI) with a high frequency of electrolyte imbalance has been described with CAR-T therapy. The aim of our study is to describe the nephrotoxicity of CAR-T therapy and to focus on AKI and the physiopathology of hypophosphatemia.
Method
A prospective single-center case series was performed which included all patients undergoing CAR-T therapy between 2020 and 2022. Clinical data included medical history, previous chemotherapy treatments, concomitant treatments, and clinical evolution. Daily monitoring of renal function, electrolytes and IL-6 was obtained after infusion of CAR-T. A urine sample was obtained on days 0, +7 and +14 with parathyroid hormone (PTH) and 25-OH vitamin D. AKI was classified according to the KDIGO criteria.
Results
40 patients received CAR-T therapy during the follow-up period. The median age was 62 years. The same number of men as women were included. The most frequent comorbidities were hypertension (27.5%), followed by diabetes (12.5%) and chronic kidney disease (12.5%). 12 patients presented AKI. Baseline serum creatinine (SCr) in patients with AKI was 0.9 mg/dL (0.68-1.04) with a SCr peak of 1.27 mg/dL (1.1-1.7). The time from CAR-T therapy infusion to SCr peak was 6.5 days (4-10). Of these 12 patients, 8 presented stage 1, 3 stage 2, and 1 stage 3 AKI. There were no differences between the AKI and non-AKI group in baseline characteristics, inflammatory markers, CRS, ICANS or hospital length stay. Hypophosphatemia was the most frequent electrolyte imbalance, occurring in 36 patients (90 %), 22 (61 %) patients experienced moderate hypophosphatemia (phosphorus < 2 mg/dL) while 14 (39 %) patients experienced mild hypophosphatemia. 29 patients (72 %) presented hypokalemia and 25 patients (62.5 %) hyponatremia. Patients with moderate hypophosphatemia had a significantly higher elevation of IL-6 but there were no differences in PTH or vitamin D (Table 1). Although there were no significant differences in fractional excretion of filtered phosphate (FEPO4), patients with moderate hypophosphatemia trend to have higher FEPO4 values.
Conclusion
Electrolyte disturbances are common in CAR-T therapy, with hypophosphatemia being the most frequent. There is probably a mechanism for renal phosphorus loss related to systemic inflammation. AKI is less frequent and has mild characteristics in these patients.
The optic nerve is not one of the areas of the CNS that can be used to demonstrate dissemination in space (DIS) within the 2017 McDonald criteria for the diagnosis of multiple sclerosis (MS). ...Objectives were (1) to assess whether optic nerve-MRI (ON-MRI), optical coherence tomography (OCT), and visual evoked potentials (VEP) detect optic nerve involvement in clinically isolated syndrome (CIS) and (2) to evaluate the contribution of the optic nerve topography to the current diagnostic criteria in a prospective, multicenter cohort.
MAGNIMS centers were invited to provide prospective data on patients with CIS who underwent a visual assessment with at least 2 of 3 investigations (ON-MRI, OCT, or VEP) within 6 months of onset. Modified DIS criteria were constructed by adding the optic nerve topography, defined by each investigation separately and any combination of them, as the fifth area of the CNS. A risk assessment analysis and the performance of the different DIS criteria were analyzed using the diagnosis of MS according to the 2017 McDonald criteria as the primary outcome and new T2 lesions and/or a second relapse as the secondary outcome.
We included 157 patients with CIS from 5 MAGNIMS centers; 60/157 (38.2%) patients presented with optic neuritis. Optic nerve involvement on ON-MRI was found in 40.2% patients at study entry and in 72.5% of those with optic neuritis.At follow-up (mean 27.9 months, SD 14.5), 111/157 patients (70.7%) were diagnosed with MS according to the 2017 McDonald criteria. Fulfilling either 2017 DIS or any modified DIS criteria conferred a similar high risk for reaching primary and secondary outcomes. The modified DIS criteria had higher sensitivity (92.5% with ON-MRI vs 88.2%), but slightly lower specificity (80.0% with GCIPL IEA ≥4 μm vs 82.2%), with overall similar accuracy (86.6% with ON-MRI vs 86.5%) than 2017 DIS criteria. Consistent results were found for secondary outcomes.
In patients with CIS, the presence of an optic nerve lesion defined by MRI, OCT, or VEP is frequently detected, especially when presenting with optic neuritis. Our study supports the addition of the optic nerve as a fifth topography to fulfill DIS criteria.
Background. Very few studies have analyzed early histologic lesions of diabetic nephropathy (DN) in patients without signs of clinical involvement (microalbuminuria). In this study, we analyzed renal ...histologic lesions in necropsies of diabetic patients with or without previous signs of DN. Methods. Histological material was analyzed from 21 autopsies of type 2 diabetes mellitus (T2DM) patients (9 with albuminuria and 12 without albuminuria) and 4 controls. Histologic lesions were evaluated according to the Tervaert classification. Results. Kidneys of diabetic patients presented significantly higher scores in most histologic indices analyzed (glomerular basal membrane thickening, mild and severe mesangial expansion, nodular sclerosis, interstitial fibrosis, and tubular atrophy) than in nondiabetic controls (p<0.01 in all cases). In contrast, no significant differences were detected between histologic scores when comparing the 21 diabetic patients with and without albuminuria. A significant percentage of cases without albuminuria showed moderate to severe histologic lesions, particularly severe mesangial expansion and severe glomerular vascular lesions. No significant differences were found in age, blood pressure, diabetes vintage, BMI, HbA1c, cholesterol, triglycerides, or treatments between the two (albuminuric vs. nonalbuminuric) T2DM patient groups. Conclusions. Our data suggest that histologic lesions of DN are present in the early stages of the disease, even without albuminuria presence. More precise and earlier metabolic control is recommended in T2DM, and monitoring of risk factors can play a role in DN development.
Background: Geocoding is the assignment of geographic coordinates to spatial points, which often are postal addresses. The error made in applying this process can introduce bias in estimates of ...spatiotemporal models in epidemiological studies. No studies have been found to measure the error made in applying this process in Spanish cities. The objective is to evaluate the errors in magnitude and direction from two free sources (Google and Yahoo) with regard to a GPS in two Spanish cities. Method: 30 addresses were geocoded with those two sources and the GPS in Santa Pola (Alicante) and Alicante city. The distances were calculated in metres (median, CI95%) between the sources and the GPS, globally and according to the status reported by each source. The directionality of the error was evaluated by calculating the location quadrant and applying a Chi-Square test. The GPS error was evaluated by geocoding 11 addresses twice at 4 days interval. Results: The overall median in Google-GPS was 23,2 metres (16,0-32,1) for Santa Pola, and 21,4 meters (14,9-31,1) for Alicante. The overall median in Yahoo was 136,0 meters (19,2-318,5) for Santa Pola, and 23,8 meters (13,6- 29,2) for Alicante. Between the 73% and 90% were geocoded by status as "exact or interpolated" (minor error), where Goggle andYahoo had a median error between 19 and 23 metres in the two cities. The GPS had a median error of 13.8 meters (6,7-17,8). No error directionality was detected. Conclusions: Google error is acceptable and stable in the two cities, so that it is a reliable source for Para medir elgeocoding addresses in Spain in epidemiological studies.
Fundamentos: Geocodificar es asignar coordenadas geográficas a puntos del espacio, frecuentemente direcciones postales. El error cometido al aplicar este proceso puede introducir un sesgo en las estimaciones de modelos espacio-temporales en estudios epidemiológicos. No se han encontrando estudios que midan este error en ciudades españolas. El objetivo es evaluar los errores en magnitud y direccionalidad de dos recursos gratuitos (Google y Yahoo) respecto a GPS en dos ciudades de España. Método: Se geocodificaron 30 direcciones aleatorias con los dos recursos citados y con GPS en Santa Pola (Alicante) y en Alicante. Se calculó la mediana y su IC95% del error en metros entre los recursos y GPS, para el total y por el status reportado. Se evaluó la direccionalidad del error calculando el cuadrante de localización y aplicando un test Chi-Cuadrado. Se evaluó el error del GPS midiendo 11 direcciones dos veces en un intervalo de 4 días. Resultados: La mediana del error total desde Google-GPS fue de 23,2 metros (16,0-32,2) para Santa Pola y 21,4 metros (14,9-31,1) en Alicante. Para Yahoo fue de 136,0 (19,2-318,5) para Santa Pola y 23,8 (13,6-29,2) para Alicante. Por status, se geocodificó entre un 73% y 90% como "exactas o interpoladas" (menor error), tanto Google como Yahoo tuvieron una mediana del error de entre 19 y 22 metros en las dos ciudades. El error del GPS fue de 13,8 (6,7-17,8) metros. No se detectó direccionalidad. Conclusiones: El error de Google es asumible y estable en las dos ciudades, siendo un recurso fiable para geocodificar direcciones postales en España en estudios epidemiológicos.
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