Review and Comparison of Computational Approaches for Joint Longitudinal and Time‐to‐Event Models

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151312/1/insr12322.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151312/2/insr12322_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151312/3/Supplement_ReviewComputationalJointModels_final.pd

The p21 cip1/waf1 cyclin-dependent kinase inhibitor enhances the cytotoxic effect of cisplatin in human ovarian carcinoma cells

The seriousness of ovarian cancer, which is related to the observed link between recurrency and cell cycle control defect, prompted us to explore the effect of ectopic expression of the cdk inhibitor p21cip1/waf1 on ovarian carcinoma chemosensitivity. The transfection of p21cip1/waf1 cDNA into SKOV3 and OVCAR3 cells led to reduction of tumor cell growth, enhanced susceptibility to cisplatin-induced apoptosis, and abolition of recurrency after cisplatin exposure. p21cip1/waf1 gene transfer allowed a marked reduction of the cisplatin concentration needed to erradicate the tumor cell population. These results suggest exploring the possible use of p21cip1/waf1 as an adjunctive to conventional chemotherapy

The nuclear immune receptor RPS4 is required for RRS1SLH1-dependent constitutive defense activation in Arabidopsis thaliana

Plant nucleotide-binding leucine-rich repeat (NB-LRR) disease resistance (R) proteins recognize specific ‘‘avirulent’’ pathogen effectors and activate immune responses. NB-LRR proteins structurally and functionally resemble mammalian Nod-like receptors (NLRs). How NB-LRR and NLR proteins activate defense is poorly understood. The divergently transcribed Arabidopsis R genes, RPS4 (resistance to Pseudomonas syringae 4) and RRS1 (resistance to Ralstonia solanacearum 1), function together to confer recognition of Pseudomonas AvrRps4 and Ralstonia PopP2. RRS1 is the only known recessive NBLRR R gene and encodes a WRKY DNA binding domain, prompting suggestions that it acts downstream of RPS4 for transcriptional activation of defense genes. We define here the early RRS1-dependent transcriptional changes upon delivery of PopP2 via Pseudomonas type III secretion. The Arabidopsis slh1 (sensitive to low humidity 1) mutant encodes an RRS1 allele (RRS1SLH1) with a single amino acid (leucine) insertion in the WRKY DNA-binding domain. Its poor growth due to constitutive defense activation is rescued at higher temperature. Transcription profiling data indicate that RRS1SLH1-mediated defense activation overlaps substantially with AvrRps4- and PopP2-regulated responses. To better understand the genetic basis of RPS4/RRS1-dependent immunity, we performed a genetic screen to identify suppressor of slh1 immunity (sushi) mutants. We show that many sushi mutants carry mutations in RPS4, suggesting that RPS4 acts downstream or in a complex with RRS1. Interestingly, several mutations were identified in a domain C-terminal to the RPS4 LRR domain. Using an Agrobacterium-mediated transient assay system, we demonstrate that the P-loop motif of RPS4 but not of RRS1SLH1 is required for RRS1SLH1 function. We also recapitulate the dominant suppression of RRS1SLH1 defense activation by wild type RRS1 and show this suppression requires an intact RRS1 P-loop. These analyses of RRS1SLH1 shed new light on mechanisms by which NB-LRR protein pairs activate defense signaling, or are held inactive in the absence of a pathogen effector

Mineração de dados: busca de conhecimento sobre a evolução do canto da família Thamnophilidae

Introdução. Descreve a utilização de uma técnica de mineração de dados sobre o canto, a biologia e o micro-habitat da família Thamnophilidae (Aves) a fim de encontrar padrões que os relacionem. Método. Uma base de dados foi construída em planilha Excel® relacionando 82 espécies da família da ave Thamnophilidae com diversos atributos referentes às características do canto, da biologia e do micro-habitat em que são encontradas. Na análise utilizou-se o algoritmo Apriori no software WEKA 3.7.1. Resultados. Ao associar os diferentes atributos de 82 espécies diferentes considerando o suporte mínimo de 10% e a confiança mínima de 90% foram encontrados 172 padrões, dos quais 42 continham um dos atributos do canto: PC1 e PC2. Os padrões que relacionavam o atributo PC2 foram os mais significativos ao indicar a relação deste com o tamanho e gênero da família. Os resultados colaboraram para gerar a hipótese de que os atributos do canto possuem comportamentos não relacionados. Conclusões. O experimento demonstrou que o algoritmo pode ser melhor aproveitado em bases de dados maiores e/ou cuja padronização dos dados apresente menor número de categorias, o que pode ser uma limitação no campo da macroecologia. Mas, ao mesmo tempo, se mostrou um instrumento alternativo para o estudo exploratório de relações entre diversos atributos, cujos resultados podem servir de objetos de análises mais aprofundadas.Introduction: Describes the use of a data mining technique about the song, biology and micro-habitat of the Thamnophilidae bird family in  order to find patterns which relate them. Method: A database was built in Excel ® spreadsheet listing 82 species of the family of the bird Thamnophilidae comprising various attributes related to bird calling features, biology and micro-habitat in which they are found. For the analysis it was used the algorithm APRIORI in the WEKA 3.7.1 software. Results: The association of the different attributes of the 82 different species, considering 10% of minimum support and 90% of minimum confidence, allowed the rescued of 172 patterns, from which 42 contained one of the song’s attributes: PC1 e PC2. The patterns which related the attribute PC2 were the most expressive ones due to its relation to the size and gender of the family. Conclusions: The experiment demonstrated that the algorithm could be better suited in larger databases and/or when the data standardization presents a lower number of categories, what could be a limitation in the macroecology field. Nonetheless, it has presented itself as an alternative instrument to the exploratory study of the relations among diverse attributes, which results could serve as objects for further analysis.Introducción: Se describe la utilización de una técnica de minería de datos sobre el canto, la biología y el micro-habitat de la familia Thamnophilidae (Aves) con el fin de encontrar estándares  que se relacionen. Metodología: Se construyó una base de datos en una planilla Excel relacionando 83 especies de la familia de las aves Thamnophilidae, con diferentes atributos referentes a las características del canto, de la biología y del micro-habitat en el cual se encontraban. En el análisis se utilizó el algoritmo Apriori en el software WEKA 3.7.1. Resultados: Al asociar los diferentes atributos de 82 especies diferentes considerando una base mínima de un 10% y una confianza mínima de 90% fueron encontrados 172 estándares, de los cuales 42 contenían dos atributos de canto: PC1 y PC2. Los estándares que relacionaban el atributo PC2 fueron los más significativos al indicar la relación de este con los tamaños y géneros de la familia. Los resultados ayudaron a generar una hipótesis de que los atributos de canto poseen comportamientos no relacionados. Conclusiones: La experiencia demostró que el algoritmo puede ser mejor aprovechado en bases de datos mayores y/o cuya estandarización de datos presente menor número de categorías, lo que puede ser una limitación en el campo de la macroecología. Pero, al mismo tiempo, se mostró un instrumento alternativo para el estudio exploratorio de relaciones entre diversos atributos, cuyos resultados pueden servir de objetos de análisis más profundos

Thru-reflect-line calibration for substrate integrated waveguide devices with tapered microstrip transitions

One of the main problems when exciting or measuring substrate integrated waveguide (SIW) devices lies in the need of a good interconnection with planar structures. In this reported work, the negative effects produced by the connectors and the tapered microstrip-to-SIW transitions are de-embedded from the measurements of the SIW structure by a thru-reflect-line calibration with an adequate and cheap SIW calibration kit.Díaz Caballero, E.; Belenguer Martínez, Á.; Esteban González, H.; Boria Esbert, VE. (2013). Thru-reflect-line calibration for substrate integrated waveguide devices with tapered microstrip transitions. Electronics Letters. 49(2):132-133. doi:10.1049/el.2012.3027S132133492Deslandes, D., & Wu, K. (2001). Integrated microstrip and rectangular waveguide in planar form. IEEE Microwave and Wireless Components Letters, 11(2), 68-70. doi:10.1109/7260.914305Henry, M., Free, C. E., Izqueirdo, B. S., Batchelor, J., & Young, P. (2009). Millimeter Wave Substrate Integrated Waveguide Antennas: Design and Fabrication Analysis. IEEE Transactions on Advanced Packaging, 32(1), 93-100. doi:10.1109/tadvp.2008.2011284Chen, X.-P., Wu, K., & Li, Z.-L. (2007). Dual-Band and Triple-Band Substrate Integrated Waveguide Filters With Chebyshev and Quasi-Elliptic Responses. IEEE Transactions on Microwave Theory and Techniques, 55(12), 2569-2578. doi:10.1109/tmtt.2007.909603Deslandes, D., & Ke Wu. (2005). Analysis and design of current probe transition from grounded coplanar to substrate integrated rectangular waveguides. IEEE Transactions on Microwave Theory and Techniques, 53(8), 2487-2494. doi:10.1109/tmtt.2005.852778Engen, G. F., & Hoer, C. A. (1979). Thru-Reflect-Line: An Improved Technique for Calibrating the Dual Six-Port Automatic Network Analyzer. IEEE Transactions on Microwave Theory and Techniques, 27(12), 987-993. doi:10.1109/tmtt.1979.1129778Chih-Jung Chen, & Tah-Hsiung Chu. (2009). Measurement of Noncoaxial Multiport Devices Up to the Intrinsic Ports. IEEE Transactions on Microwave Theory and Techniques, 57(5), 1230-1236. doi:10.1109/tmtt.2009.201735

Changes in suspected adverse drug reaction reporting via the Yellow Card scheme in Wales following the introduction of a National Reporting Indicator

AIMS: This study aimed to assess the impact of a National Reporting Indicator (NRI) on rates of reporting of suspected adverse drug reactions using the Yellow Card scheme following the introduction of the NRI in Wales (UK) in April 2014. METHODS: Yellow Card reporting data for general practitioners and other reporting groups in Wales and England for the financial years 2014–15 (study period 1) and 2015–16 (study period 2) were obtained from the Medicines and Healthcare Products Regulatory Agency and compared with those for 2013–14 (pre‐NRI control period). RESULTS: The numbers of Yellow Cards submitted by general practitioners in Wales were 271, 665 and 870 in the control period, study period 1 and study period 2, respectively. This is equivalent to an increase of 145% in study period 1 and 221% in study period 2 compared with the 12‐month control period (2013–14). Corresponding increases in England were 17% and 37%, respectively (P < .001 chi–squared test). The numbers of Yellow Cards submitted by other groups in Wales were 906, 795 and 947 in each of the study periods. CONCLUSIONS: Introduction of the NRI corresponded with a significant increase in the number of Yellow Cards submitted by general practitioners in Wales. General practitioner reporting rates continued to increase year on year through to 2018–19 with the NRI still in place. No concomitant change was found in reporting rates by other groups in the health boards in Wales

The PRK/Rubisco shunt strongly influences Arabidopsis seed metabolism and oil accumulation, affecting more than carbon recycling

The carbon efficiency of storage lipid biosynthesis from imported sucrose in green Brassicaceae seeds is proposed to be enhanced by the PRK/Rubisco shunt, in which ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) acts outside the context of the Calvin–Benson–Bassham cycle to recycle CO2 molecules released during fatty acid synthesis. This pathway utilizes metabolites generated by the nonoxidative steps of the pentose phosphate pathway. Photosynthesis provides energy for reactions such as the phosphorylation of ribulose 5-phosphate by phosphoribulokinase (PRK). Here, we show that loss of PRK in Arabidopsis thaliana (Arabidopsis) blocks photoautotrophic growth and is seedling-lethal. However, seeds containing prk embryos develop normally, allowing us to use genetics to assess the importance of the PRK/Rubisco shunt. Compared with nonmutant siblings, prk embryos produce one-third less lipids—a greater reduction than expected from simply blocking the proposed PRK/Rubisco shunt. However, developing prk seeds are also chlorotic and have elevated starch contents compared with their siblings, indicative of secondary effects. Overexpressing PRK did not increase embryo lipid content, but metabolite profiling suggested that Rubisco activity becomes limiting. Overall, our findings show that the PRK/Rubisco shunt is tightly integrated into the carbon metabolism of green Arabidopsis seeds, and that its manipulation affects seed glycolysis, starch metabolism, and photosynthesis.ISSN:1040-4651ISSN:1531-298XISSN:1532-298

A Repeated Measures Experiment of Green Exercise to Improve Self-Esteem in UK School Children

Exercising in natural, green environments creates greater improvements in adult's self-esteem than exercise undertaken in urban or indoor settings. No comparable data are available for children. The aim of this study was to determine whether so called 'green exercise' affected changes in self-esteem; enjoyment and perceived exertion in children differently to urban exercise. We assessed cardiorespiratory fitness (20 m shuttle-run) and self-reported physical activity (PAQ-A) in 11 and 12 year olds (n = 75). Each pupil completed two 1.5 mile timed runs, one in an urban and another in a rural environment. Trials were completed one week apart during scheduled physical education lessons allocated using a repeated measures design. Self-esteem was measured before and after each trial, ratings of perceived exertion (RPE) and enjoyment were assessed after completing each trial. We found a significant main effect (F (1,74), = 12.2, p<0.001), for the increase in self-esteem following exercise but there was no condition by exercise interaction (F (1,74), = 0.13, p = 0.72). There were no significant differences in perceived exertion or enjoyment between conditions. There was a negative correlation (r = -0.26, p = 0.04) between habitual physical activity and RPE during the control condition, which was not evident in the green exercise condition (r = -0.07, p = 0.55). Contrary to previous studies in adults, green exercise did not produce significantly greater increases in self-esteem than the urban exercise condition. Green exercise was enjoyed more equally by children with differing levels of habitual physical activity and has the potential to engage less active children in exercise. © 2013 Reed et al

Antidepressant prescribing patterns and adverse events following introduction of a National Prescribing Indicator to monitor dosulepin usage in Wales

Aims: Limiting use of the antidepressant dosulepin has been encouraged due to associated risks of toxicity. In April 2011, the All Wales Medicines Strategy Group introduced a National Prescribing Indicator (NPI) to monitor dosulepin usage. The aim of this study was to investigate antidepressant prescribing patterns, and selected adverse events in patients prescribed dosulepin following introduction of the NPI. Methods: An e‐cohort study was conducted. Adult patients receiving regular dosulepin prescriptions between October 2010 and March 2011 were included. Characteristics of patients who were continued on dosulepin, were switched to an alternative antidepressant or whose dosulepin was discontinued following introduction of the NPI were compared. Results: In total, 4121 patients were included. Of these, 1947 (47%) continued dosulepin, 1487 (36%) were switched and 692 (17%) discontinued. Of the 692 who discontinued, 92% did not receive a prescription for another antidepressant during the follow‐up period. Patients whose dosulepin was discontinued were older and were less commonly coprescribed benzodiazepines. During follow‐up, recorded incidence of selected adverse events was low across all groups and no significant difference was observed. Conclusion: Over half of patients had discontinued dosulepin at the end of the period when the NPI was in place. Further interventions may have been required to have a greater impact on prescribing. This study provides some reassurance that dosulepin discontinuation can be a successful strategy, and that the risk of the adverse events investigated was unlikely to have been greater in those who had dosulepin discontinued than in those in whom dosulepin had been continued

Avaliação da aptidão cardiorrespiratória por meio de protocolo submáximo em idosos com transtorno de humor e doença de Parkinson

CONTEXTO: Evidências demonstram benefícios para a saúde mental com o treinamento aeróbico orientado em percentuais do VO2max, indicando a importância dessa variável para a prática clínica. OBJETIVO: Validar um método para estimar o VO2max por meio de um protocolo submáximo em idosos com diagnóstico clínico de transtorno depressivo maior (DM) e doença de Parkinson (DP). MÉTODOS: A amostra foi composta por 18 pacientes (64,22 ± 9,92 anos; sete pacientes com DM e 11 com DP). Foram realizadas três avaliações: I) estadiamento da doença, II) mensuração direta de VO2max e III) teste de esforço submáximo. Foi realizada regressão linear para verificar a precisão de estimativa do VO2max estabelecido na ergoespirometria pelo VO2max predito no teste submáximo. Também foi analisada a concordância de Bland-Altman entre os procedimentos. RESULTADOS: A análise de regressão mostrou que os valores de VO2max estimados pelo protocolo submáximo associam-se com o VO2max medido, tanto no valor absoluto (R² = 0,65; EPE = 0,26 ; p < 0,001) quanto no relativo (R² = 0,56; EPE = 3,70; p < 0,001). A análise de concordância de Bland-Altman mostrou boa associação entre as duas medidas. CONCLUSÃO: O VO2max predito por meio do protocolo submáximo demonstrou satisfatória validade de critério e simples execução comparado à ergoespirometria.BACKGROUND: Evidence has shown benefits for mental health through aerobic training oriented in percentage of VO2max, indicating the importance of this variable for clinical practice. OBJECTIVE: To validate a method for estimating VO2max using a submaximal protocol in elderly patients with clinically diagnosis as major depressive disorder (MDD) and Parkinson's disease (PD). METHODS: The sample comprised 18 patients (64.22 ± 9.92 years) with MDD (n = 7) and with PD (n = 11). Three evaluations were performed: I) disease staging, II) direct measurement of VO2max and III) submaximal exercise test. Linear regression was performed to verify the accuracy of estimation in VO2max established in ergospirometry and the predicted VO2max from the submaximal test measurement. We also analyzed the correlation between the Bland-Altman procedures. RESULTS: The regression analysis showed that VO2max values estimated by submaximal protocol associated with the VO2max measured, both in absolute values (R² = 0.65; SEE = 0.26; p < 0.001) and the relative (R² = 0.56; SEE = 3.70; p < 0.001). The Bland-Altman plots for analysis of agreement of showed a good correlation between the two measures. DISCUSSION: The VO2max predicted by submaximal protocol demonstrated satisfactory criterion validity and simple execution compared to ergospirometry