Comorbid neuropathology and atypical presentation of Alzheimer's disease

IntroductionAlzheimer's disease (AD) neuropathological changes present with amnestic and nonamnestic (atypical) syndromes. The contribution of comorbid neuropathology as a substratum of atypical expression of AD remains under investigated.MethodsWe examined whether atypical AD exhibited increased comorbid neuropathology compared to typical AD and if such neuropathologies contributed to the accelerated clinical decline in atypical AD.ResultsWe examined 60 atypical and 101 typical AD clinicopathological cases. The number of comorbid pathologies was similar between the groups (p = 0.09). Argyrophilic grain disease was associated with atypical presentation (p = 0.008) after accounting for sex, age of onset, and disease duration. Vascular brain injury was more common in typical AD (p = 0.022). Atypical cases had a steeper Mini-Mental Status Examination (MMSE) decline over time (p = 0.033).DiscussionComorbid neuropathological changes are unlikely to contribute to atypical AD presentation and the steeper cognitive decline seen in this cohort.HighlightsAutopsy cohort of 60 atypical and 101 typical AD; does comorbid pathology explain atypical presentation?Atypical versus Typical AD: No significant differences in comorbid neuropathologies were found (p = 0.09).Argyrophilic Grain Disease Association: significantly correlates with atypical AD presentations, suggesting a unique neuropathological pattern (p = 0.008).Vascular Brain Injury Prevalence: Vascular brain injury is more common in typical AD than in atypical AD (p = 0.022).Cognitive Decline in Atypical AD: Atypical AD patients experience a steeper cognitive decline measured by MMSE than those with typical AD despite lacking more comorbid neuropathology, highlighting the severity of atypical AD pathogenesis (p = 0.033)

Formación socioemocional desde los sectores de aprendizaje : aprendizajes vitales

En este cuadernillo algunos profesionales, especialistas de cada Sector de Aprendizaje, exponen competencias vitales para el desarrollo y la vida humana propias de su especialidad. El aprendizaje de objetivos relativos a competencias propias de cada Sector de Aprendizaje, puede salvar vidas y cambiar historias de vida. Las competencias que aborda el texto en cada subsector están prescritas en los objetivos del currículo chileno, conforme a lo que llamamos tridimensionalidad curricular (contenidos, habilidades y actitudes). No siempre les otorgamos el valor que tienen para el desarrollo y la seguridad personal, y tampoco estamos suficientemente conscientes de las implicancias. Tampoco las implicancias fatales que tiene el no aprenderlas

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

Background Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. Methods In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH,non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2–F3, or F1 with at least oneaccompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpointsfor the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2–F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. Findings Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1–F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2–F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1–F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). Interpretation Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes

Research and Design of a Routing Protocol in Large-Scale Wireless Sensor Networks

无线传感器网络，作为全球未来十大技术之一，集成了传感器技术、嵌入式计算技术、分布式信息处理和自组织网技术，可实时感知、采集、处理、传输网络分布区域内的各种信息数据，在军事国防、生物医疗、环境监测、抢险救灾、防恐反恐、危险区域远程控制等领域具有十分广阔的应用前景。 本文研究分析了无线传感器网络的已有路由协议，并针对大规模的无线传感器网络设计了一种树状路由协议，它根据节点地址信息来形成路由，从而简化了复杂繁冗的路由表查找和维护，节省了不必要的开销，提高了路由效率，实现了快速有效的数据传输。 为支持此路由协议本文提出了一种自适应动态地址分配算——ADAR（AdaptiveDynamicAddre...As one of the ten high technologies in the future, wireless sensor network, which is the integration of micro-sensors, embedded computing, modern network and Ad Hoc technologies, can apperceive, collect, process and transmit various information data within the region. It can be used in military defense, biomedical, environmental monitoring, disaster relief, counter-terrorism, remote control of haz...学位：工学硕士院系专业：信息科学与技术学院通信工程系_通信与信息系统学号：2332007115216

Propuesta de mejora para incrementar la eficiencia en la entrega de los pedidos empleando gestión del inventario y almacenamiento en una empresa fabricante de ataúdes

El objetivo de este trabajo de investigación es mejorar la eficiencia de la entrega perfecta de pedidos para los operadores logísticos. Para ello se desarrolló un modelo de gestión de almacenes utilizando herramientas de logística ajustada. Las principales causas de las ineficiencias en el cumplimiento perfecto de los pedidos son los errores de selección, la desorganización del inventario, los métodos inadecuados de asignación de inventario y las discrepancias entre el inventario del sistema y el inventario real. Para todos los problemas anteriores se desarrolló un modelo que incluía diferentes herramientas: 5S, diseño de trazado, clasificación ABC, FIFO y optimización de rutas. Abordar este tema es importante en el estudio de caso ya que reducirá su impacto económico, es decir. costos adicionales por combustible, bienes de reemplazo y horas extras. La implementación del modelo desarrollado requiere de la participación activa de los directivos de la empresa y de los trabajadores del almacén. Para validar el modelo, ejecutamos un programa piloto y la implementación del modelo resultó en un aumento del 89 % en la eficiencia de entrega perfecta de pedidos y una reducción del 11 % en el tiempo de preparación de pedidos. Además, otra razón para realizar esta investigación es conectar más herramientas para obtener mejores resultados. Este artículo proporciona más información sobre las herramientas utilizadas en otros campos y las herramientas que se pueden utilizar en las cadenas de suministro.The objective of this research work is to improve the efficiency of seamless order delivery for logistics operators. For this purpose, a warehouse management model was developed using lean logistics tools. The main causes of inefficiencies in perfect order fulfillment are picking errors, inventory disorganization, inadequate inventory allocation methods, and discrepancies between system inventory and actual inventory. For all of the above problems, a model was developed that included different tools: 5S, layout design, ABC classification, FIFO and route optimization. Addressing this issue is important in the case study as it will reduce its economic impact, i.e. additional costs for fuel, replacement goods and overtime. The implementation of the developed model requires the active participation of the company's management and warehouse workers. To validate the model, we ran a pilot program and the implementation of the model resulted in an 89 % increase in perfect order delivery efficiency and an 11 % reduction in order picking time. In addition, another reason for conducting this research is to connect more tools for better results. This article provides more information about tools used in other fields and tools that can be used in supply chains.Trabajo de Suficiencia Profesiona

Effect of Maturity on the Measurements of Soot Volume Fraction by the Auto-compensating Laser-induced Incandescence Technique

International audienceSoot is a major byproduct of incomplete combustion of hydrocarbon fuels and biomass burning. Soot is also commonly known as black carbon after emissions. Accurate measurements of soot concentrations at the exhaust of combustion systems are of great importance for emission control and assessing the effectiveness of combustion and fuel technologies on soot emission reduction. Laser-induced incandescence (LII) has been found widespread use for measurements of carbonaceous and metal nanoparticles in many different applications.The auto-compensating LII (AC-LII) technique has become one of the popular in-situ real-time optical method for both in-flame and exhaust soot measurement. In AC-LII, the absolute LII signals at two different spectral bands in the visible to near-infrared are detected and the laser-heated soot particle temperature is determined through the principle of two-color pyrometry. Then the soot volume fraction can be inferred from the soot temperature and one of the two LII signal. In the current AC-LII data analysis, it is implicitly assumed that the soot to be measured is mature and the absorption functions at the two detection wavelengths are equal. Recent studies have revealed that soot emitted from difference combustion sources displays size-dependent absorption property, an indication that soot emitted from different sources may have different maturity. Soot maturity can be characterized by the Angstrom absorption exponent and less mature soot displays a wavelength-dependent soot absorption function. Neglect of the wavelength-dependent soot absorption function results in overestimation of soot temperature and hence underestimation of soot volume fraction.In this study, the effect of soot maturity on AC-LII measured soot volume fraction was analyzed and quantified by comparing the AC-LII measurements with light extinction measurements in a laminar coflow diffusion flame

Effect of Maturity on the Measurements of Soot Volume Fraction by the Auto-compensating Laser-induced Incandescence Technique

International audienceSoot is a major byproduct of incomplete combustion of hydrocarbon fuels and biomass burning. Soot is also commonly known as black carbon after emissions. Accurate measurements of soot concentrations at the exhaust of combustion systems are of great importance for emission control and assessing the effectiveness of combustion and fuel technologies on soot emission reduction. Laser-induced incandescence (LII) has been found widespread use for measurements of carbonaceous and metal nanoparticles in many different applications.The auto-compensating LII (AC-LII) technique has become one of the popular in-situ real-time optical method for both in-flame and exhaust soot measurement. In AC-LII, the absolute LII signals at two different spectral bands in the visible to near-infrared are detected and the laser-heated soot particle temperature is determined through the principle of two-color pyrometry. Then the soot volume fraction can be inferred from the soot temperature and one of the two LII signal. In the current AC-LII data analysis, it is implicitly assumed that the soot to be measured is mature and the absorption functions at the two detection wavelengths are equal. Recent studies have revealed that soot emitted from difference combustion sources displays size-dependent absorption property, an indication that soot emitted from different sources may have different maturity. Soot maturity can be characterized by the Angstrom absorption exponent and less mature soot displays a wavelength-dependent soot absorption function. Neglect of the wavelength-dependent soot absorption function results in overestimation of soot temperature and hence underestimation of soot volume fraction.In this study, the effect of soot maturity on AC-LII measured soot volume fraction was analyzed and quantified by comparing the AC-LII measurements with light extinction measurements in a laminar coflow diffusion flame