Numerical solution of the Dirichlet initial boundary value problem for the heat equation in exterior 3-dimensional domains using integral equations

A numerical method for the Dirichlet initial boundary value problem for the heat equation in the exterior and unbounded region of a smooth closed simply connected 3-dimensional domain is proposed and investigated. This method is based on a combination of a Laguerre transformation with respect to the time variable and an integral equation approach in the spatial variables. Using the Laguerre transformation in time reduces the parabolic problem to a sequence of stationary elliptic problems which are solved by a boundary layer approach giving a sequence of boundary integral equations of the first kind to solve. Under the assumption that the boundary surface of the solution domain has a one-to-one mapping onto the unit sphere, these integral equations are transformed and rewritten over this sphere. The numerical discretisation and solution are obtained by a discrete projection method involving spherical harmonic functions. Numerical results are included.

Mapping Transnational Crime in El Salvador: New Trends and Lessons from Colombia

Since El Salvador’s civil war formally ended in 1992 the small Central American nation has undergone profound social changes and significant reforms. However, few changes have been as important or as devastating as the nation’s emergence as a central hub in the transnational criminal “pipeline” or series of recombinant, overlapping chains of routes and actors that illicit organizations use to traffic in drugs, money weapons, human being, endangered animals and other products. The erasing of the once-clear ideological lines that drove the civil war and the ability of erstwhile enemies to join forces in criminal enterprises in the post-war period is an enduring and dangerous characteristic of El Salvador’s transnational criminal evolution. Trained, elite cadres from both sides, with few legitimate job opportunities, found their skills were marketable in the growing criminal structures. The groups moved from kidnapping and extortion to providing protection services to transnational criminal organizations to becoming integral parts of the organizations themselves. The demand for specialized military and transportation services in El Salvador have exploded as the Mexican DTOs consolidate their hold on the cocaine market and their relationships with the transportista networks, which is still in flux. The value of their services has risen dramatically also because of the fact that multiple Mexican DTOs, at war with each other in Mexico and seeking to physically control the geographic space of the lucrative pipeline routes in from Guatemala to Panama, are eager to increase their military capabilities and intelligence gathering capacities. The emergence of multiple non-state armed groups, often with significant ties to the formal political structure (state) through webs of judicial, legislative and administrative corruption, has some striking parallels to Colombia in the 1980s, where multiple types of violence ultimately challenged the sovereignty of state and left a lasting legacy of embedded corruption within the nation’s political structure. Organized crime in El Salvador is now transnational in nature and more integrated into stronger, more versatile global networks such as the Mexican DTOs. It is a hybrid of both local crime – with gangs vying for control off specific geographic space so they can extract payment for the safe passage of illicit products – and transnational groups that need to use that space to successfully move their products. These symbiotic relationships are both complex and generally transient in nature but growing more consolidated and dangerous.

Measurability characteristics mapping for large volume metrology instruments selection

Measurement and verification of products and processes during the early design is attracting increasing interest from high value manufacturing industries. Measurement planning is deemed as an effective means to facilitate the integration of the metrology activity into a wider range of production processes. However, the literature reveals that there are very few research efforts in this field, especially regarding large volume metrology. This paper presents a novel approach to accomplish instruments selection, the first stage of measurement planning process, by mapping measurability characteristics between specific measurement assignments and instruments.

A compendium of myeloma-associated chromosomal copy number abnormalities and their prognostic value.

To obtain a comprehensive genomic profile of presenting multiple myeloma cases we performed high-resolution single nucleotide polymorphism mapping array analysis in 114 samples alongside 258 samples analyzed by U133 Plus 2.0 expression array (Affymetrix). We examined DNA copy number alterations and loss of heterozygosity (LOH) to define the spectrum of minimally deleted regions in which relevant genes of interest can be found. The most frequent deletions are located at 1p (30%), 6q (33%), 8p (25%), 12p (15%), 13q (59%), 14q (39%), 16q (35%), 17p (7%), 20 (12%), and 22 (18%). In addition, copy number-neutral LOH, or uniparental disomy, was also prevalent on 1q (8%), 16q (9%), and X (20%), and was associated with regions of gain and loss. Based on fluorescence in situ hybridization and expression quartile analysis, genes of prognostic importance were found to be located at 1p (FAF1, CDKN2C), 1q (ANP32E), and 17p (TP53). In addition, we identified common homozygously deleted genes that have functions relevant to myeloma biology. Taken together, these analyses indicate that the crucial pathways in myeloma pathogenesis include the nuclear factor-κB pathway, apoptosis, cell-cycle regulation, Wnt signaling, and histone modifications. This study was registered at http://isrctn.org as ISRCTN68454111.

Aplicação de um value stream map nos serviços após venda automóvel

O projeto desenvolvido tem como objetivo principal a melhoria da eficiência na prestação de serviços de reparação de chapa e pintura na Caetano Auto Colisão, através da aplicação de ferramentas associadas à filosofia Lean. Apesar das ferramentas e técnicas lean estarem bem exploradas nas empresas de produção e manufatura, o mesmo não se verifica em relação às empresas da área dos serviços. O Value Stream Mapping é uma ferramenta lean que consiste no mapeamento do fluxo de materiais e informação necessários para a realização das atividades (que acrescentam e não acrescentam valor), desempenhadas pelos colaboradores, fornecedores e distribuidores, desde a obtenção do pedido do cliente até à entrega final do serviço. Através desta ferramenta é possível identificar as atividades que não acrescentam valor para o processo e propor medidas de melhoria que resultem na eliminação ou redução das mesmas. Com base neste conceito, foi realizado o mapeamento do processo de prestação de serviços de chapa e pintura e identificados os focos de ineficiência. A partir desta análise foram sugeridas melhorias que têm como objetivo atingir o estado futuro proposto assim como tornar o processo mais eficiente. Duas destas melhorias passaram pela implementação dos 5S na sala das tintas e pela elaboração de um relatório A3 para o centro de lavagens. O projeto realizado permitiu o estudo de um problema real numa empresa de serviços, bem como a proposta de um conjunto de melhorias que a médio prazo se espera virem a contribuir para a melhoria da eficiência na prestação de serviços de chapa e pintura.

Seeing Turkish state formation processes: Mapping language and education census data

Language provides an interesting lens to look at state-building processes because of its cross-cutting nature. For example, in addition to its symbolic value and appeal, a national language has other roles in the process, including: (a) becoming the primary medium of communication which permits the nation to function efficiently in its political and economic life, (b) promoting social cohesion, allowing the nation to develop a common culture, and (c) forming a primordial basis for self-determination. Moreover, because of its cross-cutting nature, language interventions are rarely isolated activities. Languages are adopted by speakers, taking root in and spreading between communities because they are legitimated by legislation, and then reproduced through institutions like the education and military systems. Pádraig Ó’ Riagáin (1997) makes a case for this observing that “Language policy is formulated, implemented, and accomplishes its results within a complex interrelated set of economic, social, and political processes which include, inter alia, the operation of other non-language state policies” (p. 45). In the Turkish case, its foundational role in the formation of the Turkish nation-state but its linkages to human rights issues raises interesting issues about how socio-cultural practices become reproduced through institutional infrastructure formation. This dissertation is a country-level case study looking at Turkey’s nation-state building process through the lens of its language and education policy development processes with a focus on the early years of the Republic between 1927 and 1970. This project examines how different groups self-identified or were self-identified (as the case may be) in official Turkish statistical publications (e.g., the Turkish annual statistical yearbooks and the population censuses) during that time period when language and ethnicity data was made publicly available. The overarching questions this dissertation explores include: 1.What were the geo-political conditions surrounding the development and influencing the Turkish government’s language and education policies? 2.Are there any observable patterns in the geo-spatial distribution of language, literacy, and education participation rates over time? In what ways, are these traditionally linked variables (language, literacy, education participation) problematic? 3.What do changes in population identifiers, e.g., language and ethnicity, suggest about the government’s approach towards nation-state building through the construction of a civic Turkish identity and institution building? Archival secondary source data was digitized, aggregated by categories relevant to this project at national and provincial levels and over the course of time (primarily between 1927 and 2000). The data was then re-aggregated into values that could be longitudinally compared and then layered on aspatial administrative maps. This dissertation contributes to existing body of social policy literature by taking an interdisciplinary approach in looking at the larger socio-economic contexts in which language and education policies are produced.

Cardiac T2-mapping using a fast gradient echo spin echo sequence - first in vitro and in vivo experience

Background: The aim of this study was the evaluation of a fast Gradient Spin Echo Technique (GraSE) for cardiac T2-mapping, combining a robust estimation of T2 relaxation times with short acquisition times. The sequence was compared against two previously introduced T2-mapping techniques in a phantom and in vivo. Methods: Phantom experiments were performed at 1.5 T using a commercially available cylindrical gel phantom. Three different T2-mapping techniques were compared: a Multi Echo Spin Echo (MESE; serving as a reference), a T2-prepared balanced Steady State Free Precession (T2prep) and a Gradient Spin Echo sequence. For the subsequent in vivo study, 12 healthy volunteers were examined on a clinical 1.5 T scanner. The three T2-mapping sequences were performed at three short-axis slices. Global myocardial T2 relaxation times were calculated and statistical analysis was performed. For assessment of pixel-by-pixel homogeneity, the number of segments showing an inhomogeneous T2 value distribution, as defined by a pixel SD exceeding 20 % of the corresponding observed T2 time, was counted. Results: Phantom experiments showed a greater difference of measured T2 values between T2prep and MESE than between GraSE and MESE, especially for species with low T1 values. Both, GraSE and T2prep resulted in an overestimation of T2 times compared to MESE. In vivo, significant differences between mean T2 times were observed. In general, T2prep resulted in lowest (52.4 +/- 2.8 ms) and GraSE in highest T2 estimates (59.3 +/- 4.0 ms). Analysis of pixel-by-pixel homogeneity revealed the least number of segments with inhomogeneous T2 distribution for GraSE-derived T2 maps. Conclusions: The GraSE sequence is a fast and robust sequence, combining advantages of both MESE and T2prep techniques, which promises to enable improved clinical applicability of T2-mapping in the future. Our study revealed significant differences of derived mean T2 values when applying different sequence designs. Therefore, a systematic comparison of different cardiac T2-mapping sequences and the establishment of dedicated reference values should be the goal of future studies.

Mapping tissue inhomogeneity in acute myocarditis: a novel analytical approach to quantitative myocardial edema imaging by T2-mapping

BACKGROUND: The purpose of the present study was to investigate the diagnostic value of T2-mapping in acute myocarditis (ACM) and to define cut-off values for edema detection. METHODS: Cardiovascular magnetic resonance (CMR) data of 31 patients with ACM were retrospectively analyzed. 30 healthy volunteers (HV) served as a control. Additionally to the routine CMR protocol, T2-mapping data were acquired at 1.5 T using a breathhold Gradient-Spin-Echo T2-mapping sequence in six short axis slices. T2-maps were segmented according to the 16-segments AHA-model and segmental T2 values as well as the segmental pixel-standard deviation (SD) were analyzed. RESULTS: Mean differences of global myocardial T2 or pixel-SD between HV and ACM patients were only small, lying in the normal range of HV. In contrast, variation of segmental T2 values and pixel-SD was much larger in ACM patients compared to HV. In random forests and multiple logistic regression analyses, the combination of the highest segmental T2 value within each patient (maxT2) and the mean absolute deviation (MAD) of log-transformed pixel-SD (madSD) over all 16 segments within each patient proved to be the best discriminators between HV and ACM patients with an AUC of 0.85 in ROC-analysis. In classification trees, a combined cut-off of 0.22 for madSD and of 68 ms for maxT2 resulted in 83% specificity and 81% sensitivity for detection of ACM. CONCLUSIONS: The proposed cut-off values for maxT2 and madSD in the setting of ACM allow edema detection with high sensitivity and specificity and therefore have the potential to overcome the hurdles of T2-mapping for its integration into clinical routine.

QTLs mapping for primary metabolites responsible of the organoleptic and nutritional characteristics of strawberry (Fragaria x ananassa)

The cultivated strawberry (Fragaria x ananassa) is the berry fruit most consumed worldwide and is well-known for its delicate flavour and nutritional properties. However, fruit quality attributes have been lost or reduced after years of traditional breeding focusing mainly on agronomical traits. To face the obstacles encountered in the improvement of cultivated crops, new technological tools, such as genomics and high throughput metabolomics, are becoming essential for the identification of genetic factors responsible of organoleptic and nutritive traits. Integration of “omics” data will allow a better understanding of the molecular and genetic mechanisms underlying the accumulation of metabolites involved in the flavour and nutritional value of the fruit. To identify genetic components affecting/controlling? fruit metabolic composition, here we present a quantitative trait loci (QTL) analysis using a 95 F1 segregating population derived from genotypes ‘1392’, selected for its superior flavour, and ‘232’ selected based in high yield (Zorrilla-Fontanesi et al., 2011; Zorrilla-Fontanesi et al., 2012). Metabolite profiling was performed on red stage strawberry fruits using gas chromatography hyphenated to time-of-flight mass spectrometry, which is a rapid and highly sensitive approach, allowing a good coverage of the central pathways of primary metabolism. Around 50 primary metabolites, including sugars, sugars derivatives, amino and organic acids, were detected and quantified after analysis in each individual of the population. QTL mapping was performed on the ‘232’ x ‘1392’ population separately over two successive years, based on the integrated linkage map (Sánchez-Sevilla et al., 2015). First, significant associations between metabolite content and molecular markers were identified by the non-parametric test of Kruskal-Wallis. Then, interval mapping (IM), as well as the multiple QTL method (MQM) allowed the identification of QTLs in octoploid strawberry. A permutation test established LOD thresholds for each metabolite and year. A total of 132 QTLs were detected in all the linkage groups over the two years for 42 metabolites out of 50. Among them, 4 (9.8%) QTLs for sugars, 9 (25%) for acids and 7 (12.7%) for amino acids were stable and detected in the two successive years. We are now studying the QTLs regions in order to find candidate genes to explain differences in metabolite content in the different individuals of the population, and we expect to identify associations between genes and metabolites which will help us to understand their role in quality traits of strawberry fruit.

Private sensors and crowdsourced rainfall data: accuracy and effectiveness for monitoring severe events and mapping pluvial flooding in urban areas

The increasing number of extreme rainfall events, combined with the high population density and the imperviousness of the land surface, makes urban areas particularly vulnerable to pluvial flooding. In order to design and manage cities to be able to deal with this issue, the reconstruction of weather phenomena is essential. Among the most interesting data sources which show great potential are the observational networks of private sensors managed by citizens (crowdsourcing). The number of these personal weather stations is consistently increasing, and the spatial distribution roughly follows population density. Precisely for this reason, they perfectly suit this detailed study on the modelling of pluvial flood in urban environments. The uncertainty associated with these measurements of precipitation is still a matter of research. In order to characterise the accuracy and precision of the crowdsourced data, we carried out exploratory data analyses. A comparison between Netatmo hourly precipitation amounts and observations of the same quantity from weather stations managed by national weather services is presented. The crowdsourced stations have very good skills in rain detection but tend to underestimate the reference value. In detail, the accuracy and precision of crowd- sourced data change as precipitation increases, improving the spread going to the extreme values. Then, the ability of this kind of observation to improve the prediction of pluvial flooding is tested. To this aim, the simplified raster-based inundation model incorporated in the Saferplaces web platform is used for simulating pluvial flooding. Different precipitation fields have been produced and tested as input in the model. Two different case studies are analysed over the most densely populated Norwegian city: Oslo. The crowdsourced weather station observations, bias-corrected (i.e. increased by 25%), showed very good skills in detecting flooded areas.

The Value Of The 2005 International Society Of Urological Pathology (isup) Modified Gleason Grading System As A Predictor Of Biochemical Recurrence After Radical Prostatectomy.

To compare time and risk to biochemical recurrence (BR) after radical prostatectomy of two chronologically different groups of patients using the standard and the modified Gleason system (MGS). Cohort 1 comprised biopsies of 197 patients graded according to the standard Gleason system (SGS) in the period 1997/2004, and cohort 2, 176 biopsies graded according to the modified system in the period 2005/2011. Time to BR was analyzed with the Kaplan-Meier product-limit analysis and prediction of shorter time to recurrence using univariate and multivariate Cox proportional hazards model. Patients in cohort 2 reflected time-related changes: striking increase in clinical stage T1c, systematic use of extended biopsies, and lower percentage of total length of cancer in millimeter in all cores. The MGS used in cohort 2 showed fewer biopsies with Gleason score ≤ 6 and more biopsies of the intermediate Gleason score 7. Time to BR using the Kaplan-Meier curves showed statistical significance using the MGS in cohort 2, but not the SGS in cohort 1. Only the MGS predicted shorter time to BR on univariate analysis and on multivariate analysis was an independent predictor. The results favor that the 2005 International Society of Urological Pathology modified system is a refinement of the Gleason grading and valuable for contemporary clinical practice.

Prognostic Value Of Dna And Mrna E6/e7 Of Human Papillomavirus In The Evolution Of Cervical Intraepithelial Neoplasia Grade 2.

This study aimed at evaluating whether human papillomavirus (HPV) groups and E6/E7 mRNA of HPV 16, 18, 31, 33, and 45 are prognostic of cervical intraepithelial neoplasia (CIN) 2 outcome in women with a cervical smear showing a low-grade squamous intraepithelial lesion (LSIL). This cohort study included women with biopsy-confirmed CIN 2 who were followed up for 12 months, with cervical smear and colposcopy performed every three months. Women with a negative or low-risk HPV status showed 100% CIN 2 regression. The CIN 2 regression rates at the 12-month follow-up were 69.4% for women with alpha-9 HPV versus 91.7% for other HPV species or HPV-negative status (P < 0.05). For women with HPV 16, the CIN 2 regression rate at the 12-month follow-up was 61.4% versus 89.5% for other HPV types or HPV-negative status (P < 0.05). The CIN 2 regression rate was 68.3% for women who tested positive for HPV E6/E7 mRNA versus 82.0% for the negative results, but this difference was not statistically significant. The expectant management for women with biopsy-confirmed CIN 2 and previous cytological tests showing LSIL exhibited a very high rate of spontaneous regression. HPV 16 is associated with a higher CIN 2 progression rate than other HPV infections. HPV E6/E7 mRNA is not a prognostic marker of the CIN 2 clinical outcome, although this analysis cannot be considered conclusive. Given the small sample size, this study could be considered a pilot for future larger studies on the role of predictive markers of CIN 2 evolution.

Predictive Value Of Phase I Trials For Safety In Later Trials And Final Approved Dose: Analysis Of 61 Approved Cancer Drugs.

Phase I trials use a small number of patients to define a maximum tolerated dose (MTD) and the safety of new agents. We compared data from phase I and registration trials to determine whether early trials predicted later safety and final dose. We searched the U.S. Food and Drug Administration (FDA) website for drugs approved in nonpediatric cancers (January 1990-October 2012). The recommended phase II dose (R2PD) and toxicities from phase I were compared with doses and safety in later trials. In 62 of 85 (73%) matched trials, the dose from the later trial was within 20% of the RP2D. In a multivariable analysis, phase I trials of targeted agents were less predictive of the final approved dose (OR, 0.2 for adopting ± 20% of the RP2D for targeted vs. other classes; P = 0.025). Of the 530 clinically relevant toxicities in later trials, 70% (n = 374) were described in phase I. A significant relationship (P = 0.0032) between increasing the number of patients in phase I (up to 60) and the ability to describe future clinically relevant toxicities was observed. Among 28,505 patients in later trials, the death rate that was related to drug was 1.41%. In conclusion, dosing based on phase I trials was associated with a low toxicity-related death rate in later trials. The ability to predict relevant toxicities correlates with the number of patients on the initial phase I trial. The final dose approved was within 20% of the RP2D in 73% of assessed trials.

Value Of Sentinel Lymph Node Biopsy In Papillary Thyroid Cancer: Initial Results Of A Prospective Trial.

The objectives of the study were to evaluate the performance of sentinel lymph node biopsy (SLNB) in detecting occult metastases in papillary thyroid carcinoma (PTC) and to correlate their presence to tumor and patient characteristics. Twenty-three clinically node-negative PTC patients (21 females, mean age 48.4 years) were prospectively enrolled. Patients were submitted to sentinel lymph node (SLN) lymphoscintigraphy prior to total thyroidectomy. Ultrasound-guided peritumoral injections of (99m)Tc-phytate (7.4 MBq) were performed. Cervical single-photon emission computed tomography and computed tomography (SPECT/CT) images were acquired 15 min after radiotracer injection and 2 h prior to surgery. Intra-operatively, SLNs were located with a gamma probe and removed along with non-SLNs located in the same neck compartment. Papillary thyroid carcinoma, SLNs and non-SLNs were submitted to histopathology analysis. Sentinel lymph nodes were located in levels: II in 34.7 % of patients; III in 26 %; IV in 30.4 %; V in 4.3 %; VI in 82.6 % and VII in 4.3 %. Metastases in the SLN were noted in seven patients (30.4 %), in non-SLN in three patients (13.1 %), and in the lateral compartments in 20 % of patients. There were significant associations between lymph node (LN) metastases and the presence of angio-lymphatic invasion (p = 0.04), extra-thyroid extension (p = 0.03) and tumor size (p = 0.003). No correlations were noted among LN metastases and patient age, gender, stimulated thyroglobulin levels, positive surgical margins, aggressive histology and multifocal lesions. Sentinel lymph node biopsy can detect occult metastases in PTC. The risk of a metastatic SLN was associated with extra-thyroid extension, larger tumors and angio-lymphatic invasion. This may help guide future neck dissection, patient surveillance and radioiodine therapy doses.

Preference Mapping Of Dulce De Leche Commercialized In Brazilian Markets.

Dulce de leche samples available in the Brazilian market were submitted to sensory profiling by quantitative descriptive analysis and acceptance test, as well sensory evaluation using the just-about-right scale and purchase intent. External preference mapping and the ideal sensory characteristics of dulce de leche were determined. The results were also evaluated by principal component analysis, hierarchical cluster analysis, partial least squares regression, artificial neural networks, and logistic regression. Overall, significant product acceptance was related to intermediate scores of the sensory attributes in the descriptive test, and this trend was observed even after consumer segmentation. The results obtained by sensometric techniques showed that optimizing an ideal dulce de leche from the sensory standpoint is a multidimensional process, with necessary adjustments on the appearance, aroma, taste, and texture attributes of the product for better consumer acceptance and purchase. The optimum dulce de leche was characterized by high scores for the attributes sweet taste, caramel taste, brightness, color, and caramel aroma in accordance with the preference mapping findings. In industrial terms, this means changing the parameters used in the thermal treatment and quantitative changes in the ingredients used in formulations.