The metabolomic window into hepatobiliary disease

The emergent discipline of metabolomics has attracted considerable research effort in hepatology. Here we review the metabolomic data for non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), cirrhosis, hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), alcoholic liver disease (ALD), hepatitis B and C, cholecystitis, cholestasis, liver transplantation, and acute hepatotoxicity in animal models. A metabolomic window has permitted a view into the changing biochemistry occurring in the transitional phases between a healthy liver and hepatocellular carcinoma or cholangiocarcinoma. Whether provoked by obesity and diabetes, alcohol use or oncogenic viruses, the liver develops a core metabolomic phenotype (CMP) that involves dysregulation of bile acid and phospholipid homeostasis. The CMP commences at the transition between the healthy liver (Phase 0) and NAFLD/NASH, ALD or viral hepatitis (Phase 1). This CMP is maintained in the presence or absence of cirrhosis (Phase 2) and whether or not either HCC or CCA (Phase 3) develops. Inflammatory signalling in the liver triggers the appearance of the CMP. Many other metabolomic markers distinguish between Phases 0, 1, 2 and 3. A metabolic remodelling in HCC has been described but metabolomic data from all four Phases demonstrate that the Warburg shift from mitochondrial respiration to cytosolic glycolysis foreshadows HCC and may occur as early as Phase 1. The metabolic remodelling also involves an upregulation of fatty acid β-oxidation, also beginning in Phase 1. The storage of triglycerides in fatty liver provides high energy-yielding substrates for Phases 2 and 3 of liver pathology. The metabolomic window into hepatobiliary disease sheds new light on the systems pathology of the liver.

Simple Estimation of Incident HIV Infection Rates in Notification Cohorts Based on Window Periods of Algorithms for Evaluation of Line-Immunoassay Result Patterns

Background Tests for recent infections (TRIs) are important for HIV surveillance. We have shown that a patient's antibody pattern in a confirmatory line immunoassay (Inno-Lia) also yields information on time since infection. We have published algorithms which, with a certain sensitivity and specificity, distinguish between incident (< = 12 months) and older infection. In order to use these algorithms like other TRIs, i.e., based on their windows, we now determined their window periods. Methods We classified Inno-Lia results of 527 treatment-naïve patients with HIV-1 infection < = 12 months according to incidence by 25 algorithms. The time after which all infections were ruled older, i.e. the algorithm's window, was determined by linear regression of the proportion ruled incident in dependence of time since infection. Window-based incident infection rates (IIR) were determined utilizing the relationship ‘Prevalence = Incidence x Duration’ in four annual cohorts of HIV-1 notifications. Results were compared to performance-based IIR also derived from Inno-Lia results, but utilizing the relationship ‘incident = true incident + false incident’ and also to the IIR derived from the BED incidence assay. Results Window periods varied between 45.8 and 130.1 days and correlated well with the algorithms' diagnostic sensitivity (R2 = 0.962; P<0.0001). Among the 25 algorithms, the mean window-based IIR among the 748 notifications of 2005/06 was 0.457 compared to 0.453 obtained for performance-based IIR with a model not correcting for selection bias. Evaluation of BED results using a window of 153 days yielded an IIR of 0.669. Window-based IIR and performance-based IIR increased by 22.4% and respectively 30.6% in 2008, while 2009 and 2010 showed a return to baseline for both methods. Conclusions IIR estimations by window- and performance-based evaluations of Inno-Lia algorithm results were similar and can be used together to assess IIR changes between annual HIV notification cohorts.

Age of cleft monazites in the eastern Tauern Window: constraints on crystallization conditions of hydrothermal monazite

Monazite-bearing Alpine clefts located in the Sonnblick region of the eastern Tauern Window, Austria, are oriented perpendicular to the foliation and lineation. Ion probe (SIMS) Th–Pb and U–Pb dating of four cleft monazites yields crystallization ages of different growth domains and aggregate regions ranging from 18.99 ± 0.51 to 15.00 ± 0.51 Ma. The crystallization ages obtained are overlapping or slightly younger than zircon fission track ages but older than zircon (U–Th)/He cooling ages from the same area. This constrains cleft monazite crystallization in this area to *300–200 �C. LA-ICP-MS data of dated hydrothermal monazites indicate that in graphite-bearing, reduced host lithologies, cleft monazite is poor in As and has higher La/Yb values and U concentrations, whereas in oxidised host rocks opposite trends are observed. Monazites show negative Eu anomalies and variable La/Yb values ranging from 520 to 6050. The positive correlation between Ca and Sr concentration indicates dissolution of plagioclase or carbonates as the source of these elements. The data show that early exhumation and cleft formation in the Tauern is related to metamorphic dome formation caused by the collision of the Adriatic with the European plate and that monazite crystallization in the clefts occurred later. Our data also demonstrate that hydrothermal monazite ages offer great potential in helping to constrain the chronology of exhumation in collisional orogens.

Time window for recanalization in basilar artery occlusion: Speculative synthesis.

Basilar artery occlusion (BAO) is one of the most devastating forms of stroke and few patients have good outcomes without recanalization. Most centers apply recanalization therapies for BAO up to 12-24 hours after symptom onset, which is a substantially longer time window than the 4.5 hours used in anterior circulation stroke. In this speculative synthesis, we discuss recent advances in BAO treatment in order to understand why and under which circumstances longer symptom duration might not necrotize the brainstem and turn therapeutic attempts futile. We raise the possibility that distinct features of the posterior circulation, e.g., highly developed, persistent collateral arterial network, reverse filling of the distal basilar artery, and delicate plasma flow siding the clot, might sustain brittle patency of brainstem perforators in the face of stepwise growth of the thrombus. Meanwhile, the tissue clock characterizing the rapid necrosis of a typical anterior circulation penumbra will not start. During this perilous time period, recanalization at any point would salvage the brainstem from eventual necrosis caused by imminent reinforcement and further building up of the clot.

Lamb Temporal Bone as a Surgical Training Model of Round Window Cochlear Implant Electrode Insertion

OBJECTIVE The preservation of residual hearing in cochlear implantation opens the door for optimal functional results. This atraumatic surgical technique requires training; however, the traditional human cadaveric temporal bones have become less available or unattainable in some institutions. This study investigates the suitability of an alternative model, using cadaveric lamb temporal bone, for surgical training of atraumatic round window electrode insertion. INTERVENTION A total of 14 lamb temporal bones were dissected for cochlear implantation by four surgeons. After mastoidectomy, visualization, and drilling of the round window niche, an atraumatic round window insertion of a Medel Flex24 electrode was performed. Electrode insertion depth and position were verified by computed tomography scans. MAIN OUTCOME MEASURE All cochleas were successfully implanted using the atraumatic round window approach; however, surgical access through the mastoid was substantially different when compared human anatomy. The mean number of intracochlear electrode contacts was 6.5 (range, 4-11) and the mean insertion depth 10.4 mm (range, 4-20 mm), which corresponds to a mean angular perimodiolar insertion depth of 229 degrees (range 67-540°). Full insertion of the electrode was not possible because of the smaller size of the lamb cochlea in comparison to that of the human. CONCLUSION The lamb temporal bone model is well suited as a training model for atraumatic cochlear implantation at the level of the round window. The minimally pneumatized mastoid as well as the smaller cochlea can help prepare a surgeon for difficult cochlear implantations. Because of substantial differences to human anatomy, it is not an adequate training model for other surgical techniques such as mastoidectomy and posterior tympanotomy as well as full electrode insertion.

Directional DBS improves therapeutic window: from model prediction to human use

Deep brain stimulation of different targets has been shown to drastically improve symptoms of a variety of neurological conditions. However, the occurrence of disabling side effects may limit the ability to deliver adequate amounts of current necessary to reach the maximal benefit. Computed models have suggested that reduction in electrode size and the ability to provide directional stimulation could increase the efficacy of such therapies. This has never been demonstrated in humans. In the present study, we assess the effect of directional stimulation compared to omnidirectional stimulation.

The impact of a cooking and gardening summer camp experience on the fruit and vegetable consumption of elementary school-aged children

Childhood obesity is a significant public health problem. Over 15 percent of children in the United States are obese, and about 25 percent of children in Texas are overweight (CDC NHANES). Furthermore, about 30 percent of elementary school aged children in Harris County, Texas are overweight or obese (Children at Risk Institute 2010). In addition to actions such as increasing physical activity, decreasing television watching and video game time, decreasing snacking on low nutrient calorie dense foods and sugar sweetened beverages, children need to consume more fruits and vegetables. According to the National Health and Nutrition Examination Survey (NHANES) from 2002, about 26 percent of U.S. children are meeting the recommendations for daily fruit intake and about 16 percent are meeting the recommendations for daily vegetable intake (CDC NHANES). In 2004, the average total intake of vegetables was 0.9 cups per day and 1.1 cups of fruit per day by children ages four to nine years old in the U.S. (CDC NHANES). Not only do children need effective nutrition education to learn about fruits and vegetables, they also need access and repeated exposure to fruits and vegetables (Anderson 2009, Briefel 2009). Nutrition education interventions that provide a structured, hands-on curriculum such as school gardens have produced significant changes in child fruit and vegetable intake (Blair 2009, McAleese 2007). To prevent childhood obesity from continuing into adolescence and adulthood, effective nutrition education interventions need to be implemented immediately and for the long-term. However, research has shown short-term nutrition education interventions such as summer camps to be effective for significant changes in child fruit and vegetable intake, preferences, and knowledge (Heim 2009). ^ A four week summer camp based on cooking and gardening was implemented at 6 Multi-Service centers in a large, urban city. The participants included children ranging in age from 7 to 14 years old (n=64). The purpose of the camp was to introduce children to their food from the seed to the plate through the utilization of gardening and culinary exercises. The summer camp activities were aimed at increasing the children's exposure, willingness to try, preferences, knowledge, and intake of fruits and vegetables. A survey was given on the first day of camp and again on the last day of camp that measured the pre- and post differences in knowledge, intake, willingness to try, and preferences of fruits and vegetables. The present study examined the short-term effectiveness of a cooking and garden-based nutrition education program on the knowledge, willingness, preferences, and intake among children aged 8 to 13 years old (n=40). The final sample of participants (n=40) was controlled for those who completed pre- and post-test surveys and who were in or above the third grade level. Results showed a statistically significant increase in the reported intake of vegetables and preferences for vegetables, specifically green beans, and fruits. There was also a significant increase in preferences for fruits among boys and participants ages 11 to 13 years. The results showed a change in the expected direction of willingness to try, preferences for vegetables, and intake of fruit, however these were not statistically significant. Interestingly, the results also showed a decrease in the intake of low nutrient calorie dense foods such as sweets and candy.^

Optimización de la composición del hueco de fachada en materia de eficiencia energética. Propuesta de indicador como herramienta para el análisis integral del elemento acristalado = Energy performance optimization of window systems. Proposal of an indicator as a tool for an integrated analysis of glazing

La hipótesis de esta tesis es: "La optimización de la ventana considerando simultáneamente aspectos energéticos y aspectos relativos a la calidad ambiental interior (confort higrotérmico, lumínico y acústico) es compatible, siempre que se conozcan y consideren las sinergias existentes entre ellos desde las primeras fases de diseño". En la actualidad se desconocen las implicaciones de muchas de las decisiones tomadas en torno a la ventana; para que su eficiencia en relación a todos los aspectos mencionados pueda hacerse efectiva es necesaria una herramienta que aporte más información de la actualmente disponible en el proceso de diseño, permitiendo así la optimización integral, en función de las circunstancias específicas de cada proyecto. En la fase inicial de esta investigación se realiza un primer acercamiento al tema, a través del estado del arte de la ventana; analizando la normativa existente, los componentes, las prestaciones, los elementos experimentales y la investigación. Se observa que, en ocasiones, altos requisitos de eficiencia energética pueden suponer una disminución de las prestaciones del sistema en relación con la calidad ambiental interior, por lo que surge el interés por integrar al análisis energético aspectos relativos a la calidad ambiental interior, como son las prestaciones lumínicas y acústicas y la renovación de aire. En este punto se detecta la necesidad de realizar un estudio integral que incorpore los distintos aspectos y evaluar las sinergias que se dan entre las distintas prestaciones que cumple la ventana. Además, del análisis de las soluciones innovadoras y experimentales se observa la dificultad de determinar en qué medida dichas soluciones son eficientes, ya que son soluciones complejas, no caracterizadas y que no están incorporadas en las metodologías de cálculo o en las bases de datos de los programas de simulación. Por lo tanto, se plantea una segunda necesidad, generar una metodología experimental para llevar a cabo la caracterización y el análisis de la eficiencia de sistemas innovadores. Para abordar esta doble necesidad se plantea la optimización mediante una evaluación del elemento acristalado que integre la eficiencia energética y la calidad ambiental interior, combinando la investigación teórica y la investigación experimental. En el ámbito teórico, se realizan simulaciones, cálculos y recopilación de información de distintas tipologías de hueco, en relación con cada prestación de forma independiente (acústica, iluminación, ventilación). A pesar de haber partido con un enfoque integrador, resulta difícil esa integración detectándose una carencia de herramientas disponible. En el ámbito experimental se desarrolla una metodología para la evaluación del rendimiento y de aspectos ambientales de aplicación a elementos innovadores de difícil valoración mediante la metodología teórica. Esta evaluación consiste en el análisis comparativo experimental entre el elemento innovador y un elemento estándar; para llevar a cabo este análisis se han diseñado dos espacios iguales, que denominamos módulos de experimentación, en los que se han incorporado los dos sistemas; estos espacios se han monitorizado, obteniéndose datos de consumo, temperatura, iluminancia y humedad relativa. Se ha realizado una medición durante un periodo de nueve meses y se han analizado y comparado los resultados, obteniendo así el comportamiento real del sistema. Tras el análisis teórico y el experimental, y como consecuencia de esa necesidad de integrar el conocimiento existente se propone una herramienta de evaluación integral del elemento acristalado. El desarrollo de esta herramienta se realiza en base al procedimiento de diagnóstico de calidad ambiental interior (CAI) de acuerdo con la norma UNE 171330 “Calidad ambiental en interiores”, incorporando el factor de eficiencia energética. De la primera parte del proceso, la parte teórica y el estado del arte, se obtendrán los parámetros que son determinantes y los valores de referencia de dichos parámetros. En base a los parámetros relevantes obtenidos se da forma a la herramienta, que consiste en un indicador de producto para ventanas que integra todos los factores analizados y que se desarrolla según la Norma UNE 21929 “Sostenibilidad en construcción de edificios. Indicadores de sostenibilidad”. ABSTRACT The hypothesis of this thesis is: "The optimization of windows considering energy and indoor environmental quality issues simultaneously (hydrothermal comfort, lighting comfort, and acoustic comfort) is compatible, provided that the synergies between these issues are known and considered from the early stages of design ". The implications of many of the decisions made on this item are currently unclear. So that savings can be made, an effective tool is needed to provide more information during the design process than the currently available, thus enabling optimization of the system according to the specific circumstances of each project. The initial phase deals with the study from an energy efficiency point of view, performing a qualitative and quantitative analysis of commercial, innovative and experimental windows. It is observed that sometimes, high-energy efficiency requirements may mean a reduction in the system's performance in relation to user comfort and health, that's why there is an interest in performing an integrated analysis of indoor environment aspects and energy efficiency. At this point a need for a comprehensive study incorporating the different aspects is detected, to evaluate the synergies that exist between the various benefits that meet the window. Moreover, from the analysis of experimental and innovative windows, a difficulty in establishing to what extent these solutions are efficient is observed; therefore, there is a need to generate a methodology for performing the analysis of the efficiency of the systems. Therefore, a second need arises, to generate an experimental methodology to perform characterization and analysis of the efficiency of innovative systems. To address this dual need, the optimization of windows by an integrated evaluation arises, considering energy efficiency and indoor environmental quality, combining theoretical and experimental research. In the theoretical field, simulations and calculations are performed; also information about the different aspects of indoor environment (acoustics, lighting, ventilation) is gathered independently. Despite having started with an integrative approach, this integration is difficult detecting lack available tools. In the experimental field, a methodology for evaluating energy efficiency and indoor environment quality is developed, to be implemented in innovative elements which are difficult to evaluate using a theoretical methodology This evaluation is an experimental comparative analysis between an innovative element and a standard element. To carry out this analysis, two equal spaces, called experimental cells, have been designed. These cells have been monitored, obtaining consumption, temperature, luminance and relative humidity data. Measurement has been performed during nine months and results have been analyzed and compared, obtaining results of actual system behavior. To advance this optimization, windows have been studied from the point of view of energy performance and performance in relation to user comfort and health: thermal comfort, acoustic comfort, lighting comfort and air quality; proposing the development of a methodology for an integrated analysis including energy efficiency and indoor environment quality. After theoretical and experimental analysis and as a result of the need to integrate existing knowledge, a comprehensive evaluation procedure for windows is proposed. This evaluation procedure is developed according to the UNE 171330 "Indoor Environmental Quality", also incorporating energy efficiency and cost as factors to evaluate. From the first part of the research process, outstanding parameters are chosen and reference values of these parameters are set. Finally, based on the parameters obtained, an indicator is proposed as windows product indicator. The indicator integrates all factors analyzed and is developed according to ISO 21929-1:2011"Sustainability in building construction. Sustainability indicators. Part 1: Framework for the development of indicators and a core set of indicators for buildings".

Home automation controller for a water-flow window

Facing the EU energy efficiency and legal scenarios related to buildings (2010/31 EU directive), new sustainable advanced concepts for envelopes are required. These innovative designs must be able to offer an elevated level of energy efficiency based on a high performance architecture. According to this, smart glazings, and particularly active water-flow glazings, represent a promising alternative to other solar control glazings, since they can reduce the building energy demand avoiding well known drawbacks as high cost, glare problems and high response time that affect to other smart glazings. This kind of glazing, as any other active one, needs to be operated by a control system. In order to operate a water-flow based window, a new controller based on an inexpensive microcontroller board has been developed

Modelization of an experimental solar test box equipped with a water-flow based window

A study on a water- ow window installed in a test box is presented. This window is composed of two glass panes separated by a chamber through water ows. The ow of water comes from an isolated tank which contains heat water. In order to fully evaluate the water- ow window performance for different room and window sizes, locations and weather conditions, a mathematical model of the whole box is needed. The proposed model, in which conduction heat transfer mechanism is the only considered, is one dimensional and unsteady based upon test box energy balance. The effect of the heat water tank, which feeds the water- ow window, is included in the model by means of a time delay in the source term. Although some previous work about moving uid chamber has been developed, air was used as heat transfer uid and no uid storage was considered. Finally a comparison between the numerical solution and the obtained experimental data is done.

Arsenic, antimony and selenium in urban soils: potential risks for human health in urban gardening

The benefits of urban agriculture are many and well documented, ranging from health improvement to community betterment, more sustainable urban development and environment protection. On the negative side, urban soils are commonly enriched in toxic trace elements that have accumulated over time through the deposition of atmospheric particles (generated by automotive traffic, heating systems, historical industrial activities and resuspended street dust), and the uncontrolled disposal of domestic, commercial and industrial wastes. This in turn has given rise to concerns about the level of exposure of urban farmers to these elements and the potential health hazards associated with this exposure. Research efforts in this field have started relatively recently and have almost systematically omitted the influence of Sb and Se, and to a lesser extent of As, although all three have proven toxic effects.

A tetracycline derivative, minocycline, reduces inflammation and protects against focal cerebral ischemia with a wide therapeutic window

The only treatment of patients with acute ischemic stroke is thrombolytic therapy, which benefits only a fraction of stroke patients. Both human and experimental studies indicate that ischemic stroke involves secondary inflammation that significantly contributes to the outcome after ischemic insult. Minocycline is a semisynthetic second-generation tetracycline that exerts antiinflammatory effects that are completely separate from its antimicrobial action. Because tetracycline treatment is clinically well tolerated, we investigated whether minocycline protects against focal brain ischemia with a wide therapeutic window. Using a rat model of transient middle cerebral artery occlusion, we show that daily treatment with minocycline reduces cortical infarction volume by 76 ± 22% when the treatment is started 12 h before ischemia and by 63 ± 35% when started even 4 h after the onset of ischemia. The treatment inhibits morphological activation of microglia in the area adjacent to the infarction, inhibits induction of IL-1β-converting enzyme, and reduces cyclooxygenase-2 expression and prostaglandin E2 production. Minocycline had no effect on astrogliosis or spreading depression, a wave of ionic transients thought to contribute to enlargement of cortical infarction. Treatment with minocycline may act directly on brain cells, because cultured primary neurons were also salvaged from glutamate toxicity. Minocycline may represent a prototype of an antiinflammatory compound that provides protection against ischemic stroke and has a clinically relevant therapeutic window.