A comparison of observed versus estimated baseline creatinine for determination of RIFLE class in patients with acute kidney injury

Methods. Data from the Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) study, a prospective observational study from 54 ICUs in 23 countries of critically ill patients with severe AKI, were analysed. The RIFLE class was determined by using observed (o) pre-morbid and estimated (e) baseline SCr values. Agreement was evaluated by correlation coefficients and Bland-Altman plots. Sensitivity analysis by chronic kidney disease (CKD) status was performed. Results. Seventy-six percent of patients (n = 1327) had a pre-morbid baseline SCr, and 1314 had complete data for evaluation. Forty-six percent had CKD. The median (IQR) values were 97 mu mol/L (79-150) for oSCr and 88 mu mol/L (71-97) for eSCr. The oSCr and eSCr determined at ICU admission and at study enrolment showed only a modest correlation (r = 0.49, r = 0.39). At ICU admission and study enrolment, eSCr misclassified 18.8% and 11.7% of patients as having AKI compared with oSCr. Exclusion of CKD patients improved the correlation between oSCr and eSCr at ICU admission and study enrolment (r = 0.90, r = 0.84) resulting in 6.6% and 4.0% being misclassified, respectively. Conclusions. While limited, estimating baseline SCr by the MDRD equation when pre-morbid SCr is unavailable would appear to perform reasonably well for determining the RIFLE categories only if and when pre-morbid GFR was near normal. However, in patients with suspected CKD, the use of MDRD to estimate baseline SCr overestimates the incidence of AKI and should not likely be used. Improved methods to estimate baseline SCr are needed.

Impact of mild acute kidney injury (AKI) on outcome after open repair of aortic aneurysms

Recently, mild AKI has been considered as a risk factor for mortality in different scenarios. We conducted a retrospective analysis of the risk factors for two distinct definitions of AKI after elective repair of aortic aneurysms. Logistic regression was carried out to identify independent risk factors for AKI ( defined as >= 25% or >= 50% increase in baseline SCr within 48 h after surgery, AKI 25% and AKI 50%, respectively) and for mortality. Of 77 patients studied ( mean age 68 +/- 10, 83% male), 57% developed AKI 25% and 33.7% AKI 50%. There were no differences between AKI and control groups regarding comorbidities and diameter of aneurysms. However, AKI patients needed a supra-renal aortic cross-clamping more frequently and were more severely ill. Overall in-hospital mortality was 27.3%, which was markedly higher in those requiring a supra-renal aortic cross-clamping. The risk factors for AKI 25% were suprarenal aortic cross-clamping ( odds ratio 5.51, 95% CI 1.05-36.12, p = 0.04) and duration of operation for AKI 25% ( OR 6.67, 95% CI 2.23-19.9, p < 0.001). For AKI 50%, in addition to those factors, post-operative use of vasoactive drugs remained as an independent factor ( OR 6.13, 95% CI 1.64-22.8, p = 0.005). The risk factors associated with mortality were need of supra-renal aortic cross-clamping ( OR 9.6, 95% CI 1.37-67.88, p = 0.02), development of AKI 50% ( OR 8.84, 95% CI 1.31-59.39, p = 0.02), baseline GFR lower than 49 mL/min ( OR 17.07, 95% CI 2.00 145.23, p = 0.009), and serum glucose > 118 mg/dL in the post-operative period ( OR 19.99, 95% CI 2.32-172.28, p = 0.006). An increase of at least 50% in baseline SCr is a common event after surgical repair of aortic aneurysms, particularly when a supra-renal aortic cross-clamping is needed. Along with baseline moderate chronic renal failure, AKI is an independent factor contributing to the high mortality found in this scenario.

Mesenchymal stromal cells up-regulate CD39 and increase adenosine production to suppress activated T-lymphocytes

Mesenchymal stromal cells (MSCs) suppress T cell responses through mechanisms not completely understood. Adenosine is a strong immunosuppressant that acts mainly through its receptor A(2a) (ADORA2A). Extracellular adenosine levels are a net result of its production (mediated by CD39 and CD73), and of its conversion into inosine by Adenosine Deaminase (ADA). Here we investigated the involvement of ADO in the immunomodulation promoted by MSCs. Human T lymphocytes were activated and cultured with or without MSCs. Compared to lymphocytes cultured without MSCs, co-cultured lymphocytes were suppressed and expressed higher levels of ADORA2A and lower levels of ADA. In co-cultures, the percentage of MSCs expressing CD39, and of T lymphocytes expressing CD73, increased significantly and adenosine levels were higher. Incubation of MSCs with media conditioned by activated T lymphocytes induced the production of adenosine to levels similar to those observed in co-cultures, indicating that adenosine production was mainly derived from MSCs. Finally, blocking ADORA2A signaling raised lymphocyte proliferation significantly. Our results suggest that some of the immunomodulatory properties of MSCs may, in part, be mediated through the modulation of components related to adenosine signaling. These findings may open new avenues for the development of new treatments for GVHD and other inflammatory diseases. (C) 2011 Elsevier B.V. All rights reserved.

Effect of stem cells seeded onto biomaterial on the progression of experimental chronic kidney disease

Different routes for the administration of bone marrow-derived cells (BMDC) have been proposed to treat the progression of chronic renal failure (CRF). We investigated whether (1) the use of bovine pericardium (BP) as a scaffold for cell therapy would retard the progression of CAF and (2) the efficacy of cell therapy differently impacts distinct degrees of CRF. We used 2/3 and 5/6 models of renal mass reduction to simulate different stages of chronicity. Treatments consisted of BP seeded with either mesenchymal or mononuclear cells implanted in the parenchyma of remnant kidney. Renal function and proteinuria were measured at days 45 and 90 after cell implantation. BMDC treatment reduced glomerulosclerosis, interstitial fibrosis and lymphocytic infiltration. Immunohistochemistry showed decreased macrophage accumulation, proliferative activity and the expression of fibronectin and alpha-smooth muscle-actin. Our results demonstrate: (1) biomaterial combined with BMDC did retard the progression of experimental CRF; (2) cellular therapy stabilized serum creatinine (sCr), improved creatinine clearance and 1/sCr slope when administered during the less severe stages of CRF; (3) treatment with combined therapy decreased glomerulosclerosis, fibrosis and the expression of fibrogenic molecules; and (4) biomaterials seeded with BMDC can be an alternative route of cellular therapy.

Distinct Effects of Delta 9-Tetrahydrocannabinol and Cannabidiol on Neural Activation During Emotional Processing

Context: Cannabis use can both increase and reduce anxiety in humans. The neurophysiological substrates of these effects are unknown. Objective: To investigate the effects of 2 main psycho-active constituents of Cannabis sativa (Delta 9-tetrahydrocannabinol [Delta 9-THC] and cannabidiol [CBD]) on regional brain function during emotional processing. Design: Subjects were studied on 3 separate occasions using an event-related functional magnetic resonance imaging paradigm while viewing faces that implicitly elicited different levels of anxiety. Each scanning session was preceded by the ingestion of either 10 mg of Delta 9-THC, 600 mg of CBD, or a placebo in a double-blind, randomized, placebo-controlled design. Participants: Fifteen healthy, English-native, right-handed men who had used cannabis 15 times or less in their life. Main Outcome Measures: Regional brain activation (blood oxygenation level-dependent response), electrodermal activity (skin conductance response [SCR]), and objective and subjective ratings of anxiety. Results: Delta 9-Tetrahydrocannabinol increased anxiety, as well as levels of intoxication, sedation, and psychotic symptoms, whereas there was a trend for a reduction in anxiety following administration of CBD. The number of SCR fluctuations during the processing of intensely fearful faces increased following administration of Delta 9-THC but decreased following administration of CBD. Cannabidiol attenuated the blood oxygenation level dependent signal in the amygdala and the anterior and posterior cingulate cortex while subjects were processing intensely fearful faces, and its suppression of the amygdalar and anterior cingulate responses was correlated with the concurrent reduction in SCR fluctuations. Delta 9-Tetrahydrocannabinol mainly modulated activation in frontal and parietal areas. Conclusions: Delta 9-Tetrahydrocannabinol and CBD had clearly distinct effects on the neural, electrodermal, and symptomatic response to fearful faces. The effects of CBD on activation in limbic and paralimbic regions may contribute to its ability to reduce autonomic arousal and subjective anxiety, whereas the anxiogenic effects of Delta 9-THC may be related to effects in other brain regions.

Serial conditional discrimination and temporal bisection in rats selectively lesioned in the dentate gyrus

In positive serial conditional discrimination, animals respond during a target stimulus when it is preceded by a feature stimulus, but they do not respond when the same target stimulus is presented alone. Moreover, the feature and target stimuli are separated from each other by an empty interval. The present work aimed to investigate if two durations (4 or 16s) of the same feature stimulus (light) could modulate the operant responses of rats to different levers (A and B) during a 5-s target stimulus (tone). In the present study, lever A was associated with the 4-s light, and lever B was associated with the 16-s light. A 5-s empty interval was included between the light and the tone. In the same training procedure, the rats were also presented with the 5-s tone without the preceding light stimuli. In these trials, the responses were not reinforced. We evaluated the hippocampal involvement of these behavioral processes by selectively lesioning the dentate gyrus with colchicine. Once trained, the rats were submitted to a test using probe trials without reinforcement. They were presented with intermediate durations of the feature stimulus (light) to obtain a temporal bisection curve recorded during the exposure to the target stimuli. The rats from both groups learned to respond with high rates during tones preceded by light and with low rates during tones presented alone, which indicated acquisition of the serial conditional discrimination. The rats were able to discriminate between the 4- and 16-s lights by correctly choosing lever A or B. In the test, the temporal bisection curves from both experimental groups showed a bisection point at the arithmetic mean between 4 and 16s. Such processes were not impaired by the dentate gyrus lesion. Thus, our results showed that different durations of a feature stimulus could result in conditional properties. However, this processing did not appear to depend on the dentate gyrus alone. (C) 2011 Published by Elsevier B.V.

Tooth loss prevalence and risk indicators in an isolated population of Brazil

Objective. The aim of this study was to assess the prevalence, extent, and risk indicators of tooth loss in an isolated population of Brazil. Material and methods. Two-hundred-and-forty-two subjects, ranging in age from 14 to 82 years (mean 36.2 years), were identified by census in an isolated population of Brazil. All consenting subjects received a full-mouth clinical (DFT index and information about missing teeth) and periodontal examination of 6 sites per tooth. Furthermore, they were interviewed using a structured written questionnaire in order to gather information about demographic, environmental, and biological variables. Results. Of the 200 subjects (80% response rate), 19 (9.5%) were edentulous, 90% had lost at least one tooth, and 39% had lost more than 8 teeth. The mean number of teeth lost was 9.5 (95% CI = 8.2-10.8). First mandibular molars were the most commonly missing teeth. In a multiple logistic regression analysis based on a theoretical hierarchical model of tooth loss, having more than 8 teeth lost was strongly associated with adult age (OR = 18.3-17.3, 95% CIs = 4.8-69.7 and 4.0-75.1) and female gender (OR = 5.9, 95% CI = 1.9-18.2) in the final model. Conclusions. Tooth loss was highly prevalent and extensive in this isolated population. Demographic and behavioral factors played an important role in tooth loss prevalence in this population.

Arsenic inhibits the repair of DNA damage induced by benzo(a)pyrene

In order to study the effect of arsenic on DNA damage, Sprague-Dawley rats were dosed with sodium arsenite (10 mg/kg) with or without 800 mug of benzo(a)pyrene (BP) by intramammilary injection. The animals were sacrificed on day 1, 3, 5, 10 and 27 and the mammary gland tissues were collected for DNA adduct measurement using a P-32 post-labeling assay. Animals dosed with arsenic alone did not show any DNA adducts. DNA adduct levels in rats dosed with BP alone reached a maximum level by day 5, reducing to 13% of this level by day 27. Adduct levels in rats dosed with arsenic and BP also reached a maximum by day 5 but only 80% of the level observed in the BP group. However, 84% of this amount still remained by day 27. The First Nucleotide Change (FNC) technique was used for the screening of 115 samples of various tissues from mice that had been chronically exposed to sodium arsenate for over 2 years revealed that inorganic arsenic did not attack the two putative hotspots (codons 131 and 154) of the hOGG1 gene. These results support the hypothesis that arsenic exerts its biological activity through DNA repair inhibition. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

Tools for testing the Solvency Capital Requirement for life insurance

Longevity risk is one of the major risks that an insurance company or a pension fund has to deal with and it is expected that its importance will grow in the near future. In agreement with these considerations, in Solvency II regulation the Standard formula furnished for calculating the Solvency Capital Requirement explicitly considers this kind of risk. According to the new European rules in our paper we suggest a multiperiod approach to evaluate the SCR for longevity risk. We propose a backtesting framework for measuring the consistency of SCR calculations for life insurance policies.

Sistema de apoio ao utilizador de transportes públicos

Nos dias de hoje usar o transporte público para nos deslocarmos de uma determinada origem para um determinado destino é uma realidade na vida da maioria das pessoas. Muitas destas deslocações fazem parte da rotina diária do cidadão, que depende destes transportes para as suas atividades do dia-a-dia. Nos últimos anos, o número de cidadãos que usa os transportes públicos como meio de deslocação tem vindo a aumentar consideravelmente. Contudo, a maioria dos operadores de transportes públicos pecam pela falta de pontualidade dos seus serviços, e pela falta de informação disponível ao cidadão acerca dos horários dos mesmos em tempo real. Tendo este problema em conta, foi desenvolvida uma solução capaz de realizar uma previsão do tempo de chegada de um transporte público, ao longo de todo o seu serviço. Previsão essa que é atualizada ao longo do percurso de forma a reduzir a margem de erro da informação apresentada. Com esta informação o cidadão pode planear melhor o seu dia e decidir qual é a melhor altura para se deslocar para a paragem, evitando ao máximo a perda de tempo à espera do seu transporte público. A solução final foi desenvolvida com a ajuda da empresa BEWARE e teve como objetivo a criação de uma aplicação web capaz de apresentar os tempos de espera dos autocarros em diferentes tipos de vista, bem como o acompanhamento do mesmo ao longo do percurso. Toda a informação utilizada na aplicação web foi criada por dois serviços de apoio que efetuam o controlo do autocarro ao longo do percurso, bem como os cálculos da previsão dos tempos de espera. O projeto foi dividido em quatro constituintes que foram repetidas durante o desenvolvimento da solução. A primeira constou na análise do problema, no levantamento e definição dos requisitos. A segunda incluiu o desenvolvimento de um algoritmo capaz de validar a posição do autocarro ao longo do seu percurso, detetando a paragem onde este se encontra e a hora de chegada à mesma. A terceira abrangeu o desenvolvimento de um algoritmo capaz de prever o tempo de chegada de um autocarro às paragens definidas na sua rota, recorrendo ao histórico de viagens realizadas anteriormente. A quarta consistiu no desenvolvimento da aplicação web, implementando todas as funcionalidades necessárias para que a aplicação consiga realizar o acompanhamento do autocarro no percurso, a consulta dos tempos de chegada e da previsão dos tempos às paragens seguintes recorrendo a três tipos de vistas diferentes, e a possibilidade de agendar notificações de forma a receber no email as previsões dos tempos de chegada nos dias e horas mais significativos para o utilizador.

Henoch-Schönlein Purpura Associated with Pulmonary Adenocarcinoma

Introduction: The Henoch-Schönlein purpura (HSP) is an immunoglobulin A (IgA)-mediated smallvessel systemic vasculitis, rare in adults. The association with solid tumours has been described, especially with lung cancer. Case Report: We present the case of a 60-year-old Caucasian male, diagnosed with lung adenocarcinoma that underwent surgical resection without (neo)adjuvant theraphy. Two months latter he was admitted for abdominal pain, purpuric rash on his lower extremities and acute kidney injury, with serum creatinine (Scr) of 2 mg/dl. Urinalysis revealed haematuria and 24h proteinuria (P24h) of 1.5 g. The serum protein electrophoresis, complement components C3 and C4, circulating immune complexes, cryoglobulins, ANCA, ANA, anti-dsDNA and the remaining immunologic study as screening for viral infections (HCV, HBV and HIV) were negative. Renal ultrasound was normal and kidney biopsy revealed mild mesangial proliferation; 2 cellular glomerular crescents and 1 fibrinoid necrosis lesion; large amounts of red blood cell casts; lymphocytic infiltration in the intertubular interstitial capillaries; moderate arteriolar hyalinosis. Immunofluorescence demonstrated mesangial and parietal deposits of IgA. The diagnosis of HSP was assumed, and the patient started prednisolone 1 mg/kg/day. Ten months after diagnosis the patient’s baseline Scr is 1.4 mg/dl with P24h of 0.18g, without haematuria. Conclusion: Although this is a rare association and the exact mechanism behind the disease is yet unknown, physicians should be aware of it. The early recognition and treatment may prevent renal disease progression.

Managing marginal capital requirements in solvency II: Analysis of a real insurance portfolio

This thesis provides a complete analysis of the Standard Capital Requirements given by Solvency II for a real insurance portfolio. We analyze the investment portfolio of BPI Vida e Pensões, an insurance company affiliated with a Portuguese bank BPI, both at security, sub-portfolio and asset class levels. By using the Standard Formula from EIOPA, Total SCR amounts to 239M€. This value is mostly explained by Market and Default Risk whereas the former is driven by Spread and Concentration Risks. Following the methodology of Leblanc (2011), we examine the Marginal Contribution of an asset to the SCR which allows for the evaluation of the risks of each security given its characteristics and interactions in the portfolio. The top contributors to the SCR are Corporate Bonds and Term Deposits. By exploring further the composition of the portfolio, our results show that slight changes in allocation of Term and Cash Deposits have severe impacts on the total Concentration and Default Risks, respectively. Also, diversification effects are very relevant by representing savings of 122M€. Finally, Solvency II represents an opportunity for the portfolio optimization. By constructing efficient frontiers, we find that as the target expected return increases, a shift from Term Deposits/ Commercial Papers to Eurozone/Peripheral and finally Equities occurs.

O impacto nos requisitos de capital de uma seguradora através da implementação de uma nova politica de resseguro

Neste projeto pretende-se explicar qual a importância que uma política de resseguro, adotada por uma empresa de seguros, no contexto do Solvência II. O desenvolvimento dessa política pretenderá ajudar a Seguradora a escolher os parâmetros contratuais de resseguro mais favoráveis à empresa, assim como definir quantos e por quais Resseguradores deverá optar nos tratados de resseguro, procurando criar uma nova política de resseguro que tenha um impato diminuto nos riscos de subscrição e de contraparte, ao mesmo tempo que garanta um retorno adequado para Companhia. A escolha das melhores soluções de resseguro serão efetuadas tendo em conta o menor custo na sua contratação e a otimização nos requisitos de capital face à necessidade de subscrição de novos negócios. Será neste ponto que se irá abordar o efeito que o risco de subscrição terá nos requisitos de capital através da criação de cenários, que terão por base a alteração de vários parâmetros. Esta análise mais específica será efetuada pela primeira vez nesta Seguradora. Os cenários criados terão em vista vários aspetos para a Seguradora, desde a otimização do custo de resseguro ao crescimento da sua carteira face ao seu apetite ao risco, através da alteração nos seus tratados de resseguro, mais especificamente nos seus parâmetros. Estas novas alterações pretendem ter impato mais favorável na sua margem de solvência face às anteriores políticas de resseguro implementadas. Em suma, pretende-se desenvolver uma nova política de resseguro que ajude a Seguradora a otimizar os seus riscos de subscrição e de contraparte, tendo em conta as análises e conclusões identificadas por cada cenário e determinar qual será o efeito nos requisitos de capital no âmbito do Solvência II.

Scaling In-Memory databases on multicores

Current computer systems have evolved from featuring only a single processing unit and limited RAM, in the order of kilobytes or few megabytes, to include several multicore processors, o↵ering in the order of several tens of concurrent execution contexts, and have main memory in the order of several tens to hundreds of gigabytes. This allows to keep all data of many applications in the main memory, leading to the development of inmemory databases. Compared to disk-backed databases, in-memory databases (IMDBs) are expected to provide better performance by incurring in less I/O overhead. In this dissertation, we present a scalability study of two general purpose IMDBs on multicore systems. The results show that current general purpose IMDBs do not scale on multicores, due to contention among threads running concurrent transactions. In this work, we explore di↵erent direction to overcome the scalability issues of IMDBs in multicores, while enforcing strong isolation semantics. First, we present a solution that requires no modification to either database systems or to the applications, called MacroDB. MacroDB replicates the database among several engines, using a master-slave replication scheme, where update transactions execute on the master, while read-only transactions execute on slaves. This reduces contention, allowing MacroDB to o↵er scalable performance under read-only workloads, while updateintensive workloads su↵er from performance loss, when compared to the standalone engine. Second, we delve into the database engine and identify the concurrency control mechanism used by the storage sub-component as a scalability bottleneck. We then propose a new locking scheme that allows the removal of such mechanisms from the storage sub-component. This modification o↵ers performance improvement under all workloads, when compared to the standalone engine, while scalability is limited to read-only workloads. Next we addressed the scalability limitations for update-intensive workloads, and propose the reduction of locking granularity from the table level to the attribute level. This further improved performance for intensive and moderate update workloads, at a slight cost for read-only workloads. Scalability is limited to intensive-read and read-only workloads. Finally, we investigate the impact applications have on the performance of database systems, by studying how operation order inside transactions influences the database performance. We then propose a Read before Write (RbW) interaction pattern, under which transaction perform all read operations before executing write operations. The RbW pattern allowed TPC-C to achieve scalable performance on our modified engine for all workloads. Additionally, the RbW pattern allowed our modified engine to achieve scalable performance on multicores, almost up to the total number of cores, while enforcing strong isolation.

Reward- and attention-related determinants of color selection in human visual cortex

Magdeburg, Univ., Fak. für Naturwiss., Diss., 2015