Trends and Emerging Areas of Agile Research: the Report on XP2014 PhD Symposium

The PhD symposium of XP2014, the 15th International Conference on Agile Software Development, was organized as a half-day event prior to the main conference program. Seven PhD candidates came from different research institutes across the globe to present their own research proposals at the symposium. The symposium was run in a lively and interactive manner. The candidates received constructive feedback on their proposals from all the symposium participants. In this report we describe the presented proposals, focusing on the content and feedback. Through them we can take a peek at the trends and emerging areas of agile research in the coming years

The Interaction of Hypotaurine and Other Sulfinates with Reactive Oxygen and Nitrogen Species:A Survey of Reaction Mechanisms

Considerable strides have been made in understanding the oxidative mechanisms involved in the final steps of the cysteine pathway leading to taurine. The oxidation of sulfinates, hypotaurine and cysteine sulfinic acid, to the respective sulfonates, taurine and cysteic acid, has never been associated with any specific enzyme. Conversely, there is strong evidence that in vivo formation of taurine and cysteic acid is the result of sulfinate interaction with a variety of biologically relevant oxidants. In the last decade, many experiments have been performed to understand whether peroxynitrite, nitrogen dioxide and carbonate radical anion could be included in the biologically relevant reactive species capable of oxidizing sulfinates. Thanks to this work, it has been possible to highlight two possible reaction mechanisms (direct and indirect reaction) of sulfinates with reactive oxygen and nitrogen species.The sulfinates oxidation, mediated by peroxynitrite, is an example of both reaction mechanisms: through a two-electron-direct-reaction with peroxynitrite or through a one-electron-indirect-transfer reaction. In the indirect mechanism, the peroxynitrite homolysis releases hydroxyl and nitrogen dioxide radical and in addition the degradation of short-lived adduct formed by peroxynitrite and CO2 can generate carbonate radical anion. The reaction of hypotaurine and cysteine sulfinic acid with peroxynitrite-derived radicals is accompanied by extensive oxygen uptake with the generation of transient intermediates, which can begin a reaction by an oxygen-dependent mechanism with the sulfonates, taurine, and cysteic acid as final products. Due to pulse radiolysis studies, it has been shown that transient sulfonyl radicals (RSO2(•)) have been produced during the oxidation of both sulfinates by one-electron transfer reaction.The purpose is to analyze all the aspects of the reactive mechanism in the sulfinic group oxidation of hypotaurine and cysteine sulfinic acid through the results obtained from our laboratory in recent years

Patient attitudes toward using computers to improve health services delivery

BACKGROUND: The aim of this study was to examine the acceptability of point of care computerized prompts to improve health services delivery among a sample of primary care patients. METHODS: Primary data collection. Cross-sectional survey. Patients were surveyed after their visit with a primary care provider. Data were obtained from patients of ten community-based primary care practices in the spring of 2001. RESULTS: Almost all patients reported that they would support using a computer before each visit to prompt their doctor to: "do health screening tests" (92%), "counsel about health behaviors (like diet and exercise)" (92%) and "change treatments for health conditions" (86%). In multivariate testing, the only variable that was associated with acceptability of the point of care computerized prompts was patient's confidence in their ability to answer questions about their health using a computer (beta = 0.39, p = .001). Concerns about data security were expressed by 36.3% of subjects, but were not related to acceptability of the prompts. CONCLUSIONS: Support for using computers to generate point of care prompts to improve quality-oriented processes of care was high in our sample, but may be contingent on patients feeling familiar with their personal medical history

Neuromuscular Blockade with Rocuronium Bromide Increases the Tolerance of Acute Normovolemic Anemia in Anesthetized Pigs

Background: The patient's individual anemia tolerance is pivotal when blood transfusions become necessary, but are not feasible for some reason. To date, the effects of neuromuscular blockade (NMB) on anemia tolerance have not been investigated. Methods: 14 anesthetized and mechanically ventilated pigs were randomly assigned to the Roc group (3.78 mg/kg rocuronium bromide followed by continuous infusion of 1 mg/kg/min, n = 7) or to the Sal group (administration of the corresponding volume of normal saline, n = 7). Subsequently, acute normovolemic anemia was induced by simultaneous exchange of whole blood for a 6% hydroxyethyl starch solution (130/0.4) until a sudden decrease of total body O-2 consumption (VO2) indicated a critical limitation of O-2 transport capacity. The Hb concentration quantified at this time point (Hb(crit)) was the primary end-point of the protocol. Secondary endpoints were parameters of hemodynamics, O-2 transport and tissue oxygenation. Results: Hb(crit) was significantly lower in the Roc group (2.4 +/- 0.5 vs. 3.2 +/- 0.7 g/dl) reflecting increased anemia tolerance. NMB with rocuronium bromide reduced skeletal muscular VO2 and total body O-2 extraction rate. As the cardiac index increased simultaneously, total body VO2 only decreased marginally in the Roc group (change of VO2 relative to baseline -1.7 +/- 0.8 vs. 3.2 +/- 1.9% in the Sal group, p < 0.05). Conclusion: Deep NMB with rocuronium bromide increases the tolerance of acute normovolemic anemia. The underlying mechanism most likely involves a reduction of skeletal muscular VO2. During acellular treatment of an acute blood loss, NMB might play an adjuvant role in situations where profound stages of normovolemic anemia have to be tolerated (e.g. bridging an unexpected blood loss until blood products become available for transfusion). Copyright (C) 2011 S. Karger AG, Base

Induction of microRNAs, mir-155, mir-222, mir-424 and mir-503, promotes monocytic differentiation through combinatorial regulation

Acute myeloid leukemia (AML) involves a block in terminal differentiation of the myeloid lineage and uncontrolled proliferation of a progenitor state. Using phorbol myristate acetate (PMA), it is possible to overcome this block in THP-1 cells (an M5-AML containing the MLL-MLLT3 fusion), resulting in differentiation to an adherent monocytic phenotype. As part of FANTOM4, we used microarrays to identify 23 microRNAs that are regulated by PMA. We identify four PMA-induced micro- RNAs (mir-155, mir-222, mir-424 and mir-503) that when overexpressed cause cell-cycle arrest and partial differentiation and when used in combination induce additional changes not seen by any individual microRNA. We further characterize these prodifferentiative microRNAs and show that mir-155 and mir-222 induce G2 arrest and apoptosis, respectively. We find mir-424 and mir-503 are derived from a polycistronic precursor mir-424-503 that is under repression by the MLL-MLLT3 leukemogenic fusion. Both of these microRNAs directly target cell-cycle regulators and induce G1 cell-cycle arrest when overexpressed in THP-1. We also find that the pro-differentiative mir-424 and mir-503 downregulate the anti-differentiative mir-9 by targeting a site in its primary transcript. Our study highlights the combinatorial effects of multiple microRNAs within cellular systems.Comment: 45 pages 5 figure

Assessment of Ergonomic Aspects in Dental Clinic Rooms

This study aimed to describe how to evaluate and quantify the ergonomic satisfaction level of dental clinics rooms. Requirements for design, production and selection of dental equipment as described in ISO/TC-106/SC-6-N-411, support more comprehensive studies for an ergonomic evaluation and ergo design of the dental workstations. It was created a checklist of ergonomics requirements which is supported by Standards ISO/FDI and acquired by mean of a literature review. According to information exposed at the document of the Ergonomics Society of Dental Ergonomics - ESDE we can consider that the elaboration of an ergonomic evaluation protocol regard to the dental workstation is an important demand for the ergonomics, particularly in relation to the performance of the ergonomic design which presents qualified to assist to dental equipment manufactures. By this means, the identification of the evaluation factors pointed in ISO/TC 106/SC 6 N 411 offers the basic information to the process of elaboration of this protocol addressed by the described general guidelines.4116103610

Professional Learning Through Everyday Work: How Finance Professionals Self-Regulate Their Learning

Professional learning is a critical component of ongoing improvement and innovation and the adoption of new practices in the workplace. Professional learning is often achieved through learning embedded in everyday work tasks. However, little is known about how professionals self-regulate their learning through regular work activities. This paper explores how professionals in the finance sector (n-30) self-regulate their learning through day-to-day work. Analysis focuses on three sub-processes of self-regulated learning that have been identified as significant predictors of good self-regulated learning at work. A key characteristic of good self-regulation is viewing learning as a form of long-term, personalised self-improvement. This study provides a foundation for future policy and planning in organisations aiming to encourage self-regulated learning

Influencia del lugar de origen en la utilización de pruebas de cribado de cáncer ginecológico en España

OBJETIVO: Analizar la asociación entre el área geográfica de procedencia en el uso de las citologías y la mamografía. MÉTODOS: Los datos analizados proceden Encuesta Nacional de Salud de España-2006 dirigida a población mayor de 16 años. La Encuesta incluye 13.422 mujeres. Las variables dependientes fueron realización de una mamografía y de una citología vaginal, ambos en los últimos 12 meses. La medida de asociación fue el odds ratio con intervalo de confianza al 95% calculado por regresión logística. RESULTADOS: Tomando como referencia la población española, la probabilidad de realizarse una mamografías entre las mujeres procedentes de África fue 0,36 (IC95% 0,21;0,62) veces menor; Europa del Este 0,40 (IC95% 0,22;0,74) veces menor; Europa Occidental, EEUU y Canadá, 0,60 (IC95% 0,43; 0,84) veces menor y América Central / Sur 0,64 (IC95% 0,52;0,81) veces menor. En relación a la prevención de cáncer de cervix, probabilidad de realizarse una citología entre las mujeres Europa del Este fue 0,38 (IC95% 0,28;0,50) veces menor que la población española, África 0,47 (IC95%:0,33;0,67) veces menor y Europa Occidental, EEUU y Canadá 0,61 (IC95% 0,46;0,81) veces menor. Dichas asociaciones fueron independientes de la edad, indicadores socioeconómicos, estado de salud y cobertura sanitaria. CONCLUSIONES: Las mujeres inmigrantes hacen menor uso de los programas de cribado que las mujeres autóctonas. Este dato podría reflejar dificultades de acceso a los programas preventivos

CRISPR-Cas9 In Vivo Gene Editing for Transthyretin Amyloidosis

BACKGROUND: Transthyretin amyloidosis, also called ATTR amyloidosis, is a life-threatening disease characterized by progressive accumulation of misfolded transthyretin (TTR) protein in tissues, predominantly the nerves and heart. NTLA-2001 is an in vivo gene-editing therapeutic agent that is designed to treat ATTR amyloidosis by reducing the concentration of TTR in serum. It is based on the clustered regularly interspaced short palindromic repeats and associated Cas9 endonuclease (CRISPR-Cas9) system and comprises a lipid nanoparticle encapsulating messenger RNA for Cas9 protein and a single guide RNA targeting TTR. METHODS: After conducting preclinical in vitro and in vivo studies, we evaluated the safety and pharmacodynamic effects of single escalating doses of NTLA-2001 in six patients with hereditary ATTR amyloidosis with polyneuropathy, three in each of the two initial dose groups (0.1 mg per kilogram and 0.3 mg per kilogram), within an ongoing phase 1 clinical study. RESULTS: Preclinical studies showed durable knockout of TTR after a single dose. Serial assessments of safety during the first 28 days after infusion in patients revealed few adverse events, and those that did occur were mild in grade. Dose-dependent pharmacodynamic effects were observed. At day 28, the mean reduction from baseline in serum TTR protein concentration was 52% (range, 47 to 56) in the group that received a dose of 0.1 mg per kilogram and was 87% (range, 80 to 96) in the group that received a dose of 0.3 mg per kilogram. CONCLUSIONS: In a small group of patients with hereditary ATTR amyloidosis with polyneuropathy, administration of NTLA-2001 was associated with only mild adverse events and led to decreases in serum TTR protein concentrations through targeted knockout of TTR. (Funded by Intellia Therapeutics and Regeneron Pharmaceuticals; ClinicalTrials.gov number, NCT04601051. opens in new tab.

Nutrient sensing modulates malaria parasite virulence

The lifestyle of intracellular pathogens, such as malaria parasites, is intimately connected to that of their host, primarily for nutrient supply. Nutrients act not only as primary sources of energy but also as regulators of gene expression, metabolism and growth, through various signalling networks that enable cells to sense and adapt to varying environmental conditions. Canonical nutrient-sensing pathways are presumed to be absent from the causative agent of malaria, Plasmodium, thus raising the question of whether these parasites can sense and cope with fluctuations in host nutrient levels. Here we show that Plasmodium blood-stage parasites actively respond to host dietary calorie alterations through rearrangement of their transcriptome accompanied by substantial adjustment of their multiplication rate. A kinome analysis combined with chemical and genetic approaches identified KIN as a critical regulator that mediates sensing of nutrients and controls a transcriptional response to the host nutritional status. KIN shares homology with SNF1/AMPKα, and yeast complementation studies suggest that it is part of a functionally conserved cellular energy-sensing pathway. Overall, these findings reveal a key parasite nutrient-sensing mechanism that is critical for modulating parasite replication and virulence