Papers by Karla Guadalupe Ramirez Alvarez
Virtual karyotyping with SNP microarrays reduces uncertainty in the diagnosis of renal epithelial... more Virtual karyotyping with SNP microarrays reduces uncertainty in the diagnosis of renal epithelial tumors
J. Univers. Comput. Sci., 2010
The situational method engineering (SME) literature is surveyed and a synoptic evaluation present... more The situational method engineering (SME) literature is surveyed and a synoptic evaluation presented in the context of formalizing and regularizing the conceptual framework and underpinning theory. Metamodels proposed for use in SME are evaluated as well as high- level process models for method construction. Method fragments and method chunks are then described formally followed by their identification and creation (from existing methods, from scratch or from past usage). Method creation is then analyzed in terms of various processes for constructing a full methodology from the method fragments/chunks. In particular, we contrast the use of the "map" technique and of the "deontic matrix" technique. The survey is concluded with an evaluation of some ideas on method tailoring and the emerging research on quality evaluation applied to SME.
Rheumatology international, Jan 7, 2018
The Knee Injury Osteoarthritis Outcome Score (KOOS) is a widely used joint-specific measure emplo... more The Knee Injury Osteoarthritis Outcome Score (KOOS) is a widely used joint-specific measure employed to evaluate pain, symptoms, activities of daily living, recreational activities, and quality of life in patients with knee osteoarthritis (OA). Although the original KOOS has been translated into many languages, a Saudi Arabic version is not available. This study aimed to culturally adapt and evaluate the psychometric properties of the Saudi Arabic version of the KOOS in patients with knee OA. The original KOOS was translated and adapted into Saudi Arabic version over six stages according to the guidelines suggested by Beaton and recommended by the American Association of Orthopedic Surgeons Outcome Committee. Patients diagnosed with knee OA (n = 136) were recruited to examine the psychometric properties, such as internal consistency that was tested using Cronbach's alpha, test-retest reliability that was analyzed using the intra-class correlation coefficient (ICC), and construct...
Revista chilena de pediatria, 2018
In recent years, there has been an increasing interest in the determinants of subjecti ve well-be... more In recent years, there has been an increasing interest in the determinants of subjecti ve well-being and happiness. In that context, life satisfaction is one of the measures used to assess subjective well-being, with emphasis in adult population. Adapt and validate (cultu rally and linguistically) the Canadian "Satisfaction with Life adapted for Children" (SWLS-C) in Chilean adolescents, in order to assess their global judgement about their own lives. Cross-sectional study, with adolescents between 10 to 18 years old, of both sexes and three socioeconomic levels in the Metropolitan region of Chile. After a process of translation and back translation, the scale SWLS-C was applied in 3 groups: cognitive interviews (n = 23) to evaluate se mantics, content, reliability and construct validity, a second group was used as pretest (n = 24) and a third for the validation of the test (n = 200). Factor analysis was performed and measurement of convergent and divergent validity. The i...
Forensic Science International, 2016
The effect of women menstrual cycle on the forensic analysis of rapes was studied in a random gro... more The effect of women menstrual cycle on the forensic analysis of rapes was studied in a random group of 170 victims aged among 10 and 51 years. Participants were grouped according to the day of the menstrual cycle in which they were at the moment of the assault. From each participant, samples of vaginal fluid were taken and analyzed for sperm cells, p30 protein, total human DNA and human male DNA. Moreover, amplification of suspect's autosomal STR and Y-STR was attempted. Suspects' autosomal STR profiles were obtained from 92 of the 101 samples in which spermatozoa were found; and Y-STR haplotype was obtained in 1 of the 9 samples where autosomal STR profiles of a male were not obtained. On the other hand, Y-STR haplotypes were obtained in 2 of the 21 samples negative for sperm cells but positive for p30 protein. Y-STR haplotypes were also obtained in 11 of the 48 samples negative for sperm cells and p30 protein. It was found that groups of participants did not differ on the recovery of sperm cells from the vaginal swabs, quantification of suspect's DNA or amplification of their STR profiles. It is concluded that the menstrual cycle phase at the moment of the sexual assault does not affect the main outcomes of the forensic investigation of rapes.
Rev Psiquiatr Clin, Sep 30, 2005
Cancer Genetics, 2015
Cytogenomic microarray analysis (CMA) offers high-resolution, genome-wide copy number information... more Cytogenomic microarray analysis (CMA) offers high-resolution, genome-wide copy number information and is widely used in clinical laboratories for diagnosis of constitutional abnormalities. The Cancer Genomics Consortium (CGC) conducted a multi-platform, multi-center clinical validation project to compare the reliability and inter-and intra-laboratory reproducibility of this technology for clinical oncology applications. Four specimen types were processed on three different microarray platforms from Affymetrix, Agilent, and Illumina. Each microarray platform was employed at two independent test sites. In a blinded manner, the results were compared to current standard methods, including karyotype, FISH or morphology. Twenty-nine CLL blood, 34 MDS bone marrow, and 30 fresh frozen renal epithelial tumor samples were assessed by all six laboratories. Thirty FFPE renal tumor samples were analyzed at the Affymetrix and Agilent test sites only. All study samples were initial diagnostic samples. Array data were analyzed at each participating site and were submitted to caArray (https://caarray.emory.edu/) for central analysis. Laboratory interpretive results were submitted to the central analysis team for comparison to the standard-of-care assays and for calculation of intra-platform reproducibility and cross-platform concordance. The results demonstrated that the three microarray platforms 1) detect clinically actionable genomic changes in cancer compatible to standard-of-care methods; 2) further define cytogenetic aberrations; 3) identify submicroscopic alterations and loss of heterozygosity (LOH); and 4) yield consistent results within and between laboratories. Based on this study, the CGC concludes that CMA is a sensitive and reliable technique for copy number and LOH assessment that can be used for clinical oncology genomic analysis.
Cancer Cytopathology, 2011
BACKGROUND: Body fluid specimens may be the first and only pathologic specimen for clinical evalu... more BACKGROUND: Body fluid specimens may be the first and only pathologic specimen for clinical evaluation in metastatic cancer cases. The challenge of identifying the tissue of origin in metastatic cancer has led to the emergence of molecular-based assays, such as the microarray-based Pathwork Tissue of Origin gene expression test. The ability to use body fluid specimens in this test would be valuable in providing diagnoses to cancer patients without clearly identifiable primary sites. In the current study, the authors evaluated the Tissue of Origin Test for use with malignant effusion specimens. METHODS: A total of 27 metastasispositive body fluid specimens from different body sites, including pleural, ascites, pericardial, and pelvic wash fluids, were obtained from patients with known diagnoses. Nine specimens from nonmalignant body fluids were included as controls. RNA was extracted from formalin-fixed, paraffin-embedded (FFPE) tissue and gene expression analysis was performed with the Tissue of Origin Test. RESULTS: Seventeen of 27 metastasis-positive samples were non-necrotic with 60% tumor and yielded sufficient RNA. Of these samples, 94.1% (16 of 17) were in agreement with the available diagnosis. Of the 9 negative control samples evaluated, 7 (77.8%) demonstrated microarray expression profiles most similar to lymphoma, which is consistent with the predominance of inflammatory cells in these specimens. CONCLUSIONS: The results of the current study demonstrated that FFPE cell blocks from cytologic body fluid specimens yield adequate diagnostic material for the Pathwork test and can be used in the workup of patients with unknown primary tumors. Cancer (Cancer Cytopathol
Pathology Case Reviews, 2010
ABSTRACT
Diagnostic Pathology, 2008
Background Renal epithelial tumors are morphologically, biologically, and clinically heterogeneou... more Background Renal epithelial tumors are morphologically, biologically, and clinically heterogeneous. Different morphologic subtypes require specific management due to markedly different prognosis and response to therapy. Each common subtype has characteristic chromosomal gains and losses, including some with prognostic value. However, copy number information has not been readily accessible for clinical purposes and thus has not been routinely used in the diagnostic evaluation of these tumors. This information can be useful for classification of tumors with complex or challenging morphology. 'Virtual karyotypes' generated using SNP arrays can readily detect characteristic chromosomal lesions in paraffin embedded renal tumors and can be used to correctly categorize the common subtypes with performance characteristics that are amenable for routine clinical use. Methods To investigate the use of virtual karyotypes for diagnostically challenging renal epithelial tumors, we evaluat...
Modern Pathology, 2011
Loss of chromosome 14 has been associated with poor outcomes in clear-cell renal cell carcinoma. ... more Loss of chromosome 14 has been associated with poor outcomes in clear-cell renal cell carcinoma. Expression of HIFa isoforms has been linked to distinct molecular phenotypes of clear-cell renal cell carcinoma. We hypothesized that chromosome 14 loss could lead to a decrease in HIF1a levels, as its gene (HIF1A) resides in this chromosome. We analyzed 112 archival clear-cell renal cell carcinoma tumor specimens with 250K SNP microarrays. We also evaluated expression of HIFa isoforms by qPCR and immunohistochemistry in a subset of 30 patients. Loss of chromosome 14q was associated with high stage (III-IV, P ¼ 0.001), high risk for recurrence (P ¼ 0.002, RR 2.78 (1.506-5.153)) and with decreased overall survival (P ¼ 0.030) in non-metastatic clear-cell renal cell carcinoma. HIF1a mRNA and protein expression was reduced in specimens with loss of 14q (P ¼ 0.014) whereas HIF2a was not. Gain of 8q was associated with decreased overall survival (Po0.0001). Our studies confirm an association between 14q loss and clinical outcome in non-metastatic clear-cell renal cell carcinoma patients and that 8q gain is a candidate prognostic marker for decreased overall survival and appears to further decrease survival in patients with 14q loss. We have also identified that differential expression of HIF1a is associated with 14q loss. Further exploration of 8q gain, 14q loss, MYC, HIF1A and EPAS1 (HIF2a) as molecular markers of tumor behavior and prognosis could aid in personalizing medicine for patients with clear-cell renal cell carcinoma.
The Journal of Pathology, 2009
PTEN haploinsufficiency is common in hormone-sensitive prostate cancer, though the incidence of g... more PTEN haploinsufficiency is common in hormone-sensitive prostate cancer, though the incidence of genomic deletion and its downstream effects have not been elucidated in clinical samples of hormone refractory prostate cancer (HRPC). Progression to androgen independence is pivotal in prostate cancer and mediated largely by the androgen receptor (AR). Since this process is distinct from metastatic progression, we examined alterations of the PTEN gene in locally advanced recurrent, non-metastatic human HRPC tissues. Retrospective analyses of PTEN deletion status were correlated with activated downstream phospho-Akt (p-Akt) pathway proteins and with the androgen receptor. The prevalence of PTEN genomic deletions in transurethral resection samples of 59 HRPC patients with known clinical outcome was assessed by four-colour FISH analyses. FISH was performed using six BAC clones spanning both flanking PTEN genomic regions and the PTEN gene locus, and a chromosome 10 centromeric probe. PTEN copy number was also evaluated in a subset of cases using single nucleotide polymorphism (SNP) arrays. In addition, the samples were immunostained with antibodies against p-Akt, p-mTOR, p-70S6, and AR. The PTEN gene was deleted in 77% of cases, with 25% showing homozygous deletions, 18% homozygous and hemizygous deletions, and 34% hemizygous deletions only. In a subset of the study group, SNP array analysis confirmed the FISH findings. PTEN genomic deletion was significantly correlated to the expression of downstream p-Akt (p < 0.0001), AR (p = 0.025), and to cancer-specific mortality (p = 0.039). PTEN deletion is common in HRPC, with bi-allelic loss correlating to disease-specific mortality and associated with Akt and AR deregulation.
Immunology, 2013
T helper type 17 (Th17) lymphocytes are found in high frequency in tumour-burdened animals and ca... more T helper type 17 (Th17) lymphocytes are found in high frequency in tumour-burdened animals and cancer patients. These lymphocytes, characterized by the production of interleukin-17 and other pro-inflammatory cytokines, have a well-defined role in the development of inflammatory and autoimmune pathologies; however, their function in tumour immunity is less clear. We explored possible opposing anti-tumour and tumour-promoting functions of Th17 cells by evaluating tumour growth and the ability to promote tumour infiltration of myeloid-derived suppressor cells (MDSC), regulatory T cells and CD4 + interferon-c + cells in a retinoic acid-like orphan receptor ct (RORct)-deficient mouse model. A reduced percentage of Th17 cells in the tumour microenvironment in RORct-deficient mice led to enhanced tumour growth, that could be reverted by adoptive transfer of Th17 cells. Differences in tumour growth were not associated with changes in the accumulation or suppressive function of MDSC and regulatory T cells but were related to a decrease in the proportion of CD4 + T cells in the tumour. Our results suggest that Th17 cells do not affect the recruitment of immunosuppressive populations but favour the recruitment of effector Th1 cells to the tumour, thereby promoting anti-tumour responses.
Diagnostic Molecular Pathology, 2010
Chromosomal imbalances are commonly seen in cancer and inherited genetic diseases. These imbalanc... more Chromosomal imbalances are commonly seen in cancer and inherited genetic diseases. These imbalances may assist in the diagnosis, prognosis, and/or therapeutic management of certain neoplasms. Several methods for detecting chromosomal imbalances, such as, fluorescent in situ hybridization, array comparative genomic hybridization, and single nucleotide polymorphism (SNP) arrays have proven useful in formalin-fixed paraffin-embedded (FFPE) tissues. Here, we report the performance and reproducibility of virtual karyotyping of FFPE tissues with Affymetrix SNP arrays. Virtual karyotypes from 442 FFPE tumor samples were generated using the Affymetrix GeneChip Mapping 10K Xba 2.0 and/or 250K Nsp SNP mapping arrays. Samples ranged from a few weeks to 17 years in archival storage. Virtual karyotypes were assessed for copy number changes, loss of heterozygosity, and acquired uniparental disomy. Overall, 75.3% of samples produced interpretable virtual karyotypes with the 10K arrays and 76.7% in the 250K arrays. Parameters for the selection of samples for hybridization were determined, which increased the success rate in both platforms to 81.3 and 92.6%, respectively. FFPE virtual karyotypes generated with both 10K Xba 2.0 and 250K Nsp arrays showed 100% concordance in intralaboratory and interlaboratory reproducibility studies. Samples older than 7 years showed decreased performance. SNP arrays are a reliable, reproducible, and robust platform for the virtual karyotyping of FFPE tumor tissues with performance characteristics adequate for clinical application. Parameters that most significantly affected sample performance were sample age and storage conditions.
American Journal of Surgical Pathology, 2009
Approximately 7 % of renal cell tumors are reported to be ''unclassified'' renal cell carcinoma (... more Approximately 7 % of renal cell tumors are reported to be ''unclassified'' renal cell carcinoma (RCC) under the current (morphology-based) classification. Genetic lesions characteristic for RCC subtypes can be identified by virtual karyotyping with single nucleotide polymorphisms (SNP) microarrays. In this study, we examined whether virtual karyotypes could be used to better classify a cohort of morphologically challenging/unclassified RCC. Tumor resection specimens from 21 patients were profiled by virtual karyotyping with Affymetrix 10K 2.0 or 250K Nsp SNP mapping arrays and were also evaluated independently by a panel of 7 genito-urinary pathologists. Tumors were classified by the established pattern of genomic imbalances based on a reference cohort of 98 cases with classic morphology and compared with the morphologic diagnosis of the pathologist panel. Virtual karyotyping analysis identified recognized patterns of chromosomal imbalances in all but 1 (16/17 or 94%) cases with successful analysis. Four cases failed owing to low DNA quality. All cases with a panel diagnosis of unclassified RCC and cases in which a majority diagnosis was not reached were classified by their virtual karyotypes. In 1 case, the molecular-based diagnosis was in disagreement with the majority diagnosis. One case with a majority diagnosis of oncocytoma showed a novel genomic pattern not previously identified in the classic morphology cohort. We conclude that virtual karyotypes generated by SNP arrays are a valuable tool for increasing diagnostic accuracy in morphologically challenging or unclassified renal neoplasms. We consider that this technique is a feasible and practical approach for resolving difficult-to-diagnose renal tumors in clinical practice.
En este articulo se muestran cuatro modelos de los sistemas MRP cerrados con incertidumbre en los... more En este articulo se muestran cuatro modelos de los sistemas MRP cerrados con incertidumbre en los componentes de produccion, como son: la capacidad necesaria de fabricacion de cada producto, el tiempo de entrega y la disponibilidad del inventario. Dichos parametros se tratan mediante la logica difusa modelizando un sistema MRP cerrado determinista. Por tanto, se presentan inicialmente tres modelos de sistema MRP cerrado, donde cada uno considera de forma independiente la incertidumbre en capacidad, tiempo de entrega y disponibilidad de inventario. Igualmente, se presenta un cuarto modelo de sistema MRP cerrado que de forma conjunta analiza la incertidumbre en los tres parametros mencionados. Cada uno de estos modelos es validado con informacion de una empresa del sector electrico colombiano, evaluando el costo total del plan de produccion, nivel de inventarios, nivel de servicio y complejidad computacional. Abstract: In this paper, we present four models of uncertainty in the MRP cl...
Veterinary Research, 2020
Infectious coryza (IC), an upper respiratory tract disease affecting chickens, is caused by Aviba... more Infectious coryza (IC), an upper respiratory tract disease affecting chickens, is caused by Avibacterium paragallinarum. The clinical manifestations of IC include nasal discharge, facial swelling, and lacrimation. This acute disease results in high morbidity and low mortality, while the course of the disease is prolonged and mortality rates are increased in cases with secondary infections. Studies regarding the immune response in infected chickens are scarce, and the local immune response is the focal point of investigation. However, a large body of work has demonstrated that severe infections can impact the systemic immune response. The objective of this study was to evaluate the systemic effects of Avibacterium paragallinarum (serovar B-1) infection on immune cells in specific pathogen-free (SPF) chickens. The current study revealed the presence of a transient circulating monocyte population endowed with high phagocytic ability and clear downregulation of major histocompatibility ...
Uploads
Papers by Karla Guadalupe Ramirez Alvarez