Success rates of re-excision after positive margins for invasive lobular carcinoma of the breast.

Rates of positive margins after surgical resection of invasive lobular carcinoma (ILC) are high (ranging from 18 to 60%), yet the efficacy of re-excision lumpReceptor subtypeectomy for clearing positive margins is unknown. Concerns about the diffuse nature of ILC may drive increased rates of completion mastectomy to treat positive margins, thus lowering breast conservation rates. We therefore determined the success rate of re-excision lumpectomy in women with ILC and positive margins after surgical resection. We identified 314 cases of stage I-III ILC treated with breast conserving surgery (BCS) at the University of California, San Francisco. Surgical procedures, pathology reports, and outcomes were analyzed using univariate and multivariate statistics and Cox-proportional hazards models. We evaluated outcomes before and after the year 2014, when new margin management consensus guidelines were published. Positive initial margins occurred in 118 (37.6%) cases. Of these, 62 (52.5%) underwent re-excision lumpectomy, which cleared the margin in 74.2%. On multivariate analysis, node negativity was significantly associated with successful re-excision (odds ratio [OR] 3.99, 95% CI 1.15-13.81, p = 0.029). After 2014, we saw fewer initial positive margins (42.7% versus 25.5%, p = 0.009), second surgeries (54.6% versus 20.2%, p < 0.001), and completion mastectomies (27.7% versus 4.5%, p < 0.001). In this large cohort of women with ILC, re-excision lumpectomy was highly successful at clearing positive margins. Additionally, positive margins and completion mastectomy rates significantly decreased over time. These findings highlight improvements in management of ILC, and suggest that completion mastectomy may not be required for those with positive margins after initial BCS

Calidad de la administración del aprendizaje en la modalidad presencial del nivel superior en la UAEM, con el apoyo de un LMS

Una de las perspectivas para balancear los indicadores en pro de la medición de la calidad en un Balanced Scorecard según Robert Kaplan y David Norton es la perspectiva clientes que trasladándolo a los términos del ámbito educativo es el usuario estudiante. En este sentido, un indicador relacionado es la satisfacción del estudiante con respecto a su evaluación del aprendizaje. Tiene que ver con la necesidad de disponer en cualquier momento y lugar con información tal como programación, contenido de actividades de aprendizaje y criterios de evaluación a realizar así como su retroalimentación personalizada. Además de disponer de las evidencias entregadas por el estudiante y calificaciones para tener claridad durante todo el proceso de enseñanza-aprendizaje e ir conformando la evaluación sin tener lugar a duda sobre las entregas y evaluación. En este trabajo de corte cualitativo refleja la perspectiva del estudiante que hace uso de un Sistema administrador del aprendizaje (LMS) como una herramienta de apoyo a la modalidad presencial en el nivel superior. Tal análisis se basa en las respuestas de los estudiantes al aplicarles una encuesta que previamente se revisó su confiabilidad, validez y objetividad

A new method for the determination of plutonium and americium using high pressure microwave digestion and alpha-spectrometry or ICP-SMS

Plutonium and americium are radionuclides particularly difficult to measure in environmental samples because they are α-emitters and therefore necessitate a careful separation before any measurement, either using radiometric methods or ICP-SMS. Recent developments in extraction chromatography resins such as Eichrom® TRU and TEVA have resolved many of the analytical problems but drawbacks such as low recovery and spectral interferences still occasionally occur. Here, we report on the use of the new Eichrom® DGA resin in association with TEVA resin and high pressure microwave acid leaching for the sequential determination of plutonium and americium in environmental samples. The method results in average recoveries of 83±15% for plutonium and 73±22% for americium (n=60), and a less than 10% deviation from reference values of four IAEA reference materials and three samples from intercomparisons exercises. The method is also suitable for measuring 239Pu in water samples at the μBq/l level, if ICP-SMS is used for the measuremen

Multiplexed direct genomic selection (MDiGS): a pooled BAC capture approach for highly accurate CNV and SNP/INDEL detection

Despite declining sequencing costs, few methods are available for cost-effective single-nucleotide polymorphism (SNP), insertion/deletion (INDEL) and copy number variation (CNV) discovery in a single assay. Commercially available methods require a high investment to a specific region and are only cost-effective for large samples. Here, we introduce a novel, flexible approach for multiplexed targeted sequencing and CNV analysis of large genomic regions called multiplexed direct genomic selection (MDiGS). MDiGS combines biotinylated bacterial artificial chromosome (BAC) capture and multiplexed pooled capture for SNP/INDEL and CNV detection of 96 multiplexed samples on a single MiSeq run. MDiGS is advantageous over other methods for CNV detection because pooled sample capture and hybridization to large contiguous BAC baits reduces sample and probe hybridization variability inherent in other methods. We performed MDiGS capture for three chromosomal regions consisting of ∼550 kb of coding and non-coding sequence with DNA from 253 patients with congenital lower limb disorders. PITX1 nonsense and HOXC11 S191F missense mutations were identified that segregate in clubfoot families. Using a novel pooled-capture reference strategy, we identified recurrent chromosome chr17q23.1q23.2 duplications and small HOXC 5′ cluster deletions (51 kb and 12 kb). Given the current interest in coding and non-coding variants in human disease, MDiGS fulfills a niche for comprehensive and low-cost evaluation of CNVs, coding, and non-coding variants across candidate regions of interest

Modelo de gestión de calidad que permita disminuir el índice de deserción en estudios de modalidad no escolarizada para nivel superior

Las estadísticas de la ANUIES (2016), indicaron que la matrícula correspondiente al nivel licenciatura en modalidad no escolarizada para el ciclo escolar 2015-2016 era de 497,646 reflejando un incremento de 26%, lo que significa que está creciendo de manera considerable. Sin embargo, el índice de deserción sigue siendo un tema a tratar lo que nos llevó en este trabajo a encontrar estrategias para disminuirlo. Se presenta la propuesta de modelo de gestión de calidad con el objetivo de encontrar alternativas que coadyuven al logro de mayores oportunidades de permanencia

Modelo de gestión de calidad que permita disminuir el índice de deserción en estudios de modalidad no escolarizada para nivel superior

Las estadísticas de la ANUIES (2016), indicaron que la matrícula correspondiente al nivel licenciatura en modalidad no escolarizada para el ciclo escolar 2015-2016 era de 497,646 reflejando un incremento de 26%, lo que significa que está creciendo de manera considerable. Sin embargo, el índice de deserción sigue siendo un tema a tratar lo que nos llevó en este trabajo a encontrar estrategias para disminuirlo. Se presenta la propuesta de modelo de gestión de calidad con el objetivo de encontrar alternativas que coadyuven al logro de mayores oportunidades de permanencia. Derivado de lo anterior, se revisaron modelos que han surgido para gestionar la calidad en el e-learning: e-quality framewok (propuesto por el Institute of Higher Education Policy and The Sloan Consortium), OLC’s Five Pillars of Quality Online Education (creado por Online Learning Consortium) y The e-Learning Maturity Model (fundado por Marshall). Con los elementos complementarios entre los modelos se generó un instrumento de recolección de datos y se aplicó en una Institución de Educación Superior. Se propuso un procedimiento para obtener resultados, los cuales permiten identificar los factores que más influyen en la deserción escolar y derivan en el planteamiento de acciones sugeridas de mejora. El procedimiento se tendría que aplicar para cada plan de estudios que tenga problema de deserción mayor con el propósito de generar resultados y estrategias ah doc. Después de haber aplicado el procedimiento en un semestre y plan de estudios específico se recomienda generar estrategias realistas para ser implementadas. Además, se recomienda volver a aplicar el instrumento para el mismo plan de estudios y después de haber implementado algunas acciones de mejora; con la finalidad de observar los cambios en la percepción del estudiante, de tal manera que el estudio se vuelva longitudinal; quizá como encuesta de satisfacción del usuario y sea aplicada de manera oficial cada semestre. También, se recomienda que el estudio se vuelva correlacional una vez que se aplique en varias universidades de México. Por otro lado, y dado que el instrumento propuesto es aplicable a los estudiantes es pertinente que el estudio se complemente con otro instrumento aplicable a los demás actores de la educación no escolarizada (sistema a distancia) para que se tengan resultados desde diferentes perspectivas

An RNA interference-based screen of transcription factor genes identifies pathways necessary for sensory regeneration in the avian inner ear

Sensory hair cells of the inner ear are the mechano-electric transducers of sound and head motion. In mammals, damage to sensory hair cells leads to hearing or balance deficits. Non-mammalian vertebrates such as birds can regenerate hair cells after injury. In a previous study, we characterized transcription factor gene expression during chicken hair cell regeneration. In those studies, a laser micro-beam or ototoxic antibiotics were used to damage the sensory epithelia (SE). The current study focused on 27 genes that were up-regulated in regenerating SE compared to untreated SE in the previous study. Those genes were knocked down by siRNA, to determine their requirement for supporting cell proliferation and to measure resulting changes in the larger network of gene expression. We identified 11 genes necessary for proliferation and also identified novel interactive relationships between many of them. Defined components of the WNT, PAX and AP1 pathways were shown to be required for supporting cell proliferation. These pathways intersect on WNT4, which is also necessary for proliferation. Among the required genes, the CCAAT enhancer binding protein, CEBPG, acts downstream of Jun Kinase and JUND in the AP1 pathway. The WNT co-receptor LRP5 acts downstream of CEBPG as does the transcription factor BTAF1. Both of these genes are also necessary for supporting cell proliferation. This is the first large scale screen of its type and suggests an important intersection between the AP1 pathway, the PAX pathway and WNT signaling in the regulation of supporting cell proliferation during inner ear hair cell regeneration

Genetic risk for aortic aneurysm in adolescent idiopathic scoliosis

BACKGROUND: Scoliosis is a feature of several genetic disorders that are also associated with aortic aneurysm, including Marfan syndrome, Loeys-Dietz syndrome, and type-IV Ehlers-Danlos syndrome. Life-threatening complications of aortic aneurysm can be decreased through early diagnosis. Genetic screening for mutations in populations at risk, such as patients with adolescent idiopathic scoliosis, may improve recognition of these disorders. METHODS: The coding regions of five clinically actionable genes associated with scoliosis (COL3A1, FBN1, TGFBR1, TGFBR2, and SMAD3) and aortic aneurysm were sequenced in 343 adolescent idiopathic scoliosis cases. Gene variants that had minor allele frequencies of <0.0001 or were present in human disease mutation databases were identified. Variants were classified as pathogenic, likely pathogenic, or variants of unknown significance. RESULTS: Pathogenic or likely pathogenic mutations were identified in 0.9% (three) of 343 adolescent idiopathic scoliosis cases. Two patients had pathogenic SMAD3 nonsense mutations consistent with type-III Loeys-Dietz syndrome and one patient had a pathogenic FBN1 mutation with subsequent confirmation of Marfan syndrome. Variants of unknown significance in COL3A1 and FBN1 were identified in 5.0% (seventeen) of 343 adolescent idiopathic scoliosis cases. Six FBN1 variants were previously reported in patients with Marfan syndrome, yet were considered variants of unknown significance based on the level of evidence. Variants of unknown significance occurred most frequently in FBN1 and were associated with greater curve severity, systemic features of Marfan syndrome, and joint hypermobility. CONCLUSIONS: Clinically actionable pathogenic mutations in genes associated with adolescent idiopathic scoliosis and aortic aneurysm are rare in patients with adolescent idiopathic scoliosis who are not suspected of having these disorders, although variants of unknown significance are relatively common. CLINICAL RELEVANCE: Routine genetic screening of all patients with adolescent idiopathic scoliosis for mutations in clinically actionable aortic aneurysm disease genes is not recommended on the basis of the high frequency of variants of unknown significance. Clinical evaluation and family history should heighten indications for genetic referral and testing