Optimal alarm systems for count processes

In many phenomena described by stochastic processes, the implementation of an alarm system becomes fundamental to predict the occurrence of future events. In this work we develop an alarm system to predict whether a count process will upcross a certain level and give an alarm whenever the upcrossing level is predicted. We consider count models with parameters being functions of covariates of interest and varying on time. This article presents classical and Bayesian methodology for producing optimal alarm systems. Both methodologies are illustrated and their performance compared through a simulation study. The work finishes with an empirical application to a set of data concerning the number of sunspot on the surface of the sun

Integer-valued autoregressive processes with periodic structure

In this paper the periodic integer-valued autoregressive model of order one with period T, driven by a periodic sequence of independent Poisson-distributed random variables, is studied in some detail. Basic probabilistic and statistical properties of this model are discussed. Moreover, parameter estimation is also addressed. Specifically, the methods of estimation under analysis are the method of moments, least squares-type and likelihood-based ones. Their performance is compared through a simulation study. (C) 2009 Elsevier B.V. All rights reserved

Synthesis of Dehydrodipeptide and N-ethyl-dehydrodipeptide Derivatives with an α-Aminoisobutyric Acid Residue

Several dipeptides with an N-benzyloxycarbonyl or an N-(tert-butyloxycarbonyl) α-aminoisobutyric acid residue and a β-hydroxyamino acid methyl ester were subjected to dehydration to form dehydrodipeptide derivatives. N-Ethylation of these dipeptides using triethyloxonium tetrafluoroborate with potassium tert-butoxide as auxiliary base led to complex mixtures that failed to render pure products. However, when the 4-nitrophenylsulfonyl protecting group was substituted for the benzyloxycarbonyl or tert-butyloxycarbonyl groups and N,N-diisopropylethylamine was substituted for potassium tert-butoxide, the dehydrodipeptide derivatives were selectively N-alkylated at the amino terminal nitrogen in fair to high yields. Alternatively, N-ethylation can be carried out prior to dehydration. Thus, through a combination of dehydration and N-ethylation procedures, it was possible to obtain dipeptides with α-aminoisobutyric acid and dehydroamino acid residues, which are N-alkylated at the amino terminal nitrogen.Foundation for Science and Technology (FCT) – Portugal and Fundo Europeu de Desenvolvimento Regional (FEDER) for financial support to Chemistry Centre of University of Minho. The NMR spectrometer Bruker Avance II+ 400 is part of the National NMR Network and was purchased in the framework of the National Program for Scientific Re-equipment; contract REDE/1517/RMN/2005, with funds from POCI 2010, FEDER and FCT.info:eu-repo/semantics/publishedVersio

Towards precision medicine in bariatric surgery prescription

Obesity is a complex, multifactorial and chronic disease. Bariatric surgery is a safe and effective treatment intervention for obesity and obesity-related diseases. However, weight loss after surgery can be highly heterogeneous and is not entirely predictable, particularly in the long-term after intervention. In this review, we present and discuss the available data on patient-related and procedure-related factors that were previously appointed as putative predictors of bariatric surgery outcomes. In addition, we present a critical appraisal of the available evidence on which factors could be taken into account when recommending and deciding which bariatric procedure to perform. Several patient-related features were identified as having a potential impact on weight loss after bariatric surgery, including age, gender, anthropometrics, obesity co-morbidities, eating behavior, genetic background, circulating biomarkers (microRNAs, metabolites and hormones), psychological and socioeconomic factors. However, none of these factors are sufficiently robust to be used as predictive factors. Overall, there is no doubt that before we long for precision medicine, there is the unmet need for a better understanding of the socio-biological drivers of weight gain, weight loss failure and weight-regain after bariatric interventions. Machine learning models targeting preoperative factors and effectiveness measurements of specific bariatric surgery interventions, would enable a more precise identification of the causal links between determinants of weight gain and weight loss. Artificial intelligence algorithms to be used in clinical practice to predict the response to bariatric surgery interventions could then be created, which would ultimately allow to move forward into precision medicine in bariatric surgery prescription

Integration of Flight Simulator 2002 with an epidemic multicast protocol

Multi-player games are increasingly popular in the Internet. This growing interest results in the need to support a high number of participants, which raises the issue of scalability, namely in what regards the ability to offer good performance in such a large-scale setting. This paper addresses the issue of designing middleware solutions to support large-scale multi-player applications. In particular, we are interested in studying the feasibility of using epidemic multicast protocols for information dissemination in multi-player games based on a peer-to-peer architecture. We have integrated a comercial multiplayer game, the Microsoft Flight Simulator 2002, with an epidemic multicast protocol appropriate to this kind of applications, the NEEM. The paper describes how this integration was achieved and presents evaluation results of the resulting prototype

Renal Dysfunction Phenotypes in Patients Undergoing Obesity Surgery

Obesity surgery candidates are at an increased risk of kidney injury, but pre-operative evaluation usually neglects kidney function assessment. This study aimed to identify renal dysfunction in candidates for bariatric surgery. To reduce the sources of bias, subjects with diabetes, prediabetes under metformin treatment, neoplastic or inflammatory diseases were excluded. Patients' (n = 192) average body mass index was 41.7 +/- 5.4 kg/m(2). Among these, 51% (n = 94) had creatinine clearance over 140 mL/min, 22.4% (n = 43) had proteinuria over 150 mg/day and 14.6% (n = 28) albuminuria over 30 mg/day. A creatinine clearance higher than 140 mL/min was associated with higher levels of proteinuria and albuminuria. Univariate analysis identified sex, glycated hemoglobin, uric acid, HDL and VLDL cholesterol as being associated with albuminuria, but not with proteinuria. On multivariate analysis, glycated hemoglobin and creatinine clearance as continuous variables were significantly associated with albuminuria. In summary, in our patient population prediabetes, lipid abnormalities and hyperuricemia were associated with albuminuria, but not with proteinuria, suggesting different disease mechanisms might be implicated. Data suggest that in obesity-associated kidney disease, tubulointerstitial injury precedes glomerulopathy. A significant proportion of obesity surgery candidates present clinically relevant albuminuria and proteinuria along with renal hyperfiltration, suggesting that routine pre-operative assessment of these parameters should be considered

Angiogenesis in the Normal Adrenal Fetal Cortex and Adrenocortical Tumors

Simple Summary Pharmacological angiogenesis modulation was robustly demonstrated to be a powerful clinical resource in oncotherapy. Adrenocortical carcinomas (ACC) often have a poor prognosis for which therapeutic options are limited. Understanding the mechanisms that regulate adrenocortical angiogenesis both under physiological conditions and in ACC could provide important clues on how these processes could be modulated for clinical purposes. This report summarizes the current knowledge on adrenal cortex angiogenesis regulation in physiological conditions and ACC. Embryonic adrenal angiogenesis is regulated by VEGF and Ang-Tie signaling pathways. VEGF angiogenic pathway was initially considered a promising therapeutic target for improving ACC prognosis. However, every single VEGF pathway-targeting clinical trial in ACC so far conducted yielded disappointing results. In contrast, the potential of Ang-Tie pathway-targeting in ACC is yet to be explored. Therefore, further investigation on the role and efficacy of modulating both Ang-Tie and VEGF pathways in ACC is still an unmet need. Angiogenesis plays an important role in several physiological and pathological processes. Pharmacological angiogenesis modulation has been robustly demonstrated to achieve clinical benefits in several cancers. Adrenocortical carcinomas (ACC) are rare tumors that often have a poor prognosis. In addition, therapeutic options for ACC are limited. Understanding the mechanisms that regulate adrenocortical angiogenesis along the embryonic development and in ACC could provide important clues on how these processes could be pharmacologically modulated for ACC treatment. In this report, we performed an integrative review on adrenal cortex angiogenesis regulation in physiological conditions and ACC. During embryonic development, adrenal angiogenesis is regulated by both VEGF and Ang-Tie signaling pathways. In ACC, early research efforts were focused on VEGF signaling and this pathway was identified as a good prognostic factor and thus a promising therapeutic target. However, every clinical trial so far conducted in ACC using VEGF pathway- targeting drugs, alone or in combination, yielded disappointing results. In contrast, although the Ang-Tie pathway has been pointed out as an important regulator of fetal adrenocortical angiogenesis, its role is yet to be explored in ACC. In the future, further research on the role and efficacy of modulating both Ang-Tie and VEGF pathways in ACC is needed

Synthesis of N-alkyl-C α, α-dimethylglycine derivatives

The application of trialkyloxonium tetrafluoroborates for N-alkylation of the nonnatural amino acid Cα, α-dimethylglycine is described. Several methyl esters of dimethylglycine protected with different amine protecting groups were subject to N-ethylation or N-methylation with triethyloxonium tetrafluoroborate or trimethyloxonium tetrafluoroborate, respectively. The corresponding N-akyl-Cα, α-dimethylglycine derivatives were obtained in good to high yields. Removal of the methyl ester rendered amino acid derivatives ready for application in peptide synthesis.Foundation for Science and Technology (FCT) – Portugal and Fundo Europeu de Desenvolvimento Regional (FEDER) for financial support to Chemistry Centre of University of Minho. The NMR spectrometer Bruker Avance II+ 400 is part of the National NMR Network and was purchased in the framework of the National Program for Scientific Re-equipment; contract REDE/1517/RMN/2005, with funds from POCI 2010, FEDER and FCT.info:eu-repo/semantics/publishedVersio

Cefaleias primárias: Causas e consequências

A cefaleia é um sintoma subjectivo e pode ser definida como uma sensação de desconforto ou dor localizada na extremidade cefálica. Esta definição inclui todas as algias cranianas, faciais e crâniofaciais. Dado este sentido lato é fácil entender que a sua prevalência na população geral seja muito elevada, sendo uma das queixas mais comuns encontradas na prática clínica. Mas, apesar do sofrimento e da incapacidade temporária a que está associada, continua a ser pouco valo-rizada pelos clínicos, não sendo, muitas vezes, devidamente diagnosticada nem adequadamente tratada. A sua prevalência na população geral é muito elevada, sendo uma das queixas mais comuns encontradas na prática clínica apesar de continuar a ser pouco valorizada pelos clínicos, não sendo, muitas vezes, devidamente diagnosticada nem adequadamente tratada

Subcutaneous Fat Necrosis Following Induced Hypothermia

A necrose gorda do tecido celular subcutâneo do recém-nascido está associada a asfixia neonatal, aspiração de mecónio, convulsões ou hipotermia. A hipercalcemia é a complicação mais frequente, podendo em alguns casos ser grave e exigir terapêutica específica. Relata-se o caso de um recém-nascido de cesariana emergente por sofrimento fetal, tendo sido submetido a protocolo de hipotermia induzida. Foi diagnosticado com necrose gorda do recém-nascido ao 11º dia de internamento. No 23º dia identificou-se hipercalcemia, tendo iniciado terapêutica com pamidronato, com consequente diminuição gradual da calcemia. Sublinha-se a necessidade da identificação rápida de necrose gorda, possibilitando antecipar a hipercalcemia e iniciar terapêutica precoce