A human ESC-based screen identifies a role for the translated lncRNA LINC00261 in pancreatic endocrine differentiation

Long noncoding RNAs (lncRNAs) are a heterogenous group of RNAs, which can encode small proteins. The extent to which developmentally regulated lncRNAs are translated and whether the produced microproteins are relevant for human development is unknown. Using a human embryonic stem cell (hESC)-based pancreatic differentiation system, we show that many lncRNAs in direct vicinity of lineage-determining transcription factors (TFs) are dynamically regulated, predominantly cytosolic, and highly translated. We genetically ablated ten such lncRNAs, most of them translated, and found that nine are dispensable for pancreatic endocrine cell development. However, deletion of LINC00261 diminishes insulin(+) cells, in a manner independent of the nearby TF FOXA2. One-by-one deletion of each of LINC00261's open reading frames suggests that the RNA, rather than the produced microproteins, is required for endocrine development. Our work highlights extensive translation of lncRNAs during hESC pancreatic differentiation and provides a blueprint for dissection of their coding and noncoding roles

Modelamiento geométrico del cambio de coordenadas UTM causadas por mudanza de referencial geodésico: Caso Sirgas - Chile

Los avances tecnológicos de las últimas décadas han permitido determinar cada vez con mayor precisión, las dimensiones, forma y campo gravitacional de la Tierra. Estas nuevas tecnologías y sus métodos de observación y análisis, admiten el uso de distintos Sistemas Geodésicos de Referencia (SGR) que hacen posible la descripción de posición de cualquier punto sobre la superficie terrestre con precisiones sub-métricas. Actualmente en Chile hay diversos SGR usados en la generación de productos cartográficos, tales como el Datum Provisorio Sudamericano de 1956 (PSAD56), el Datum Sudamericano de 1969 (SAD69) y el nuevo Sistema de Referencia Geocéntrico para las Américas (SIRGAS). Este último, a diferencia de los dos anteriores, es un sistema geocéntrico actual, compatible en precisión y exactitud con las modernas tecnologías de posicionamiento. Actualmente, el Instituto Geográfico Militar de Chile (IGM) promueve la adopción del nuevo sistema SIRGAS e indica el modelo y los parámetros oficiales de transformación para la cartografía nacional a escala 1:50.000. Con la adopción de SIRGAS, una cantidad significativa de documentos cartográficos, en pleno uso actualmente, deberán ser transformados o adecuados al nuevo referencial geodésico. Existen diversos métodos y modelos, propuestos en la geodesia, para la transformación de valores de coordenadas asociados a un SGR en valores de coordenadas asociados a otro SGR. En el presente trabajo se realiza un análisis del impacto del cambio de referencial geodésico SIRGAS en la geometría de los rasgos representados en el sistema de proyección Universal Transversa de Mercator, para el caso de Chile continental sudamericano. Posteriormente, se definen modelos y parámetros alternativos al procedimiento clásico de transformación de coordenadas. Los resultados muestran que los modelos alternativos son eficaces en el caso de Chile

Are large clinical trials in orthopaedic trauma justified?

Background: The objective of this analysis is to evaluate the necessity of large clinical trials using FLOW trial data. Methods: The FLOW pilot study and definitive trial were factorial trials evaluating the effect of different irrigation solutions and pressures on re-operation. To explore treatment effects over time, we analyzed data from the pilot and definitive trial in increments of 250 patients until the final sample size of 2447 patients was reached. At each increment we calculated the relative risk (RR) and associated 95% confidence interval (CI) for the treatment effect, and compared the results that would have been reported at the smaller enrolments with those seen in the final, adequately powered study. Results: The pilot study analysis of 89 patients and initial incremental enrolments in the FLOW definitive trial favored low pressure compared to high pressure (RR: 1.50, 95% CI: 0.75-3.04; RR: 1.39, 95% CI: 0.60-3.23, respectively), which is in contradiction to the final enrolment, which found no difference between high and low pressure (RR: 1.04, 95% CI: 0.81-1.33). In the soap versus saline comparison, the FLOW pilot study suggested that re-operation rate was similar in both the soap and saline groups (RR: 0.98, 95% CI: 0.50-1.92), whereas the FLOW definitive trial found that the re-operation rate was higher in the soap treatment arm (RR: 1.28, 95% CI: 1.04-1.57). Conclusions: Our findings suggest that studies with smaller sample sizes would have led to erroneous conclusions in the management of open fracture wounds. Trial registration: NCT01069315 (FLOW Pilot Study) Date of Registration: February 17, 2010, NCT00788398 (FLOW Definitive Trial) Date of Registration: November 10, 2008

Seizure prediction : ready for a new era

Acknowledgements: The authors acknowledge colleagues in the international seizure prediction group for valuable discussions. L.K. acknowledges funding support from the National Health and Medical Research Council (APP1130468) and the James S. McDonnell Foundation (220020419) and acknowledges the contribution of Dean R. Freestone at the University of Melbourne, Australia, to the creation of Fig. 3.Peer reviewe

Transient criminal subcultures and the crimes they commit against the elderley : implications for continuing criminal justice and community education

The purpose of this research was to study the subculture of American adult male Gypsies involved in organized professional criminality. Identifying these criminal groups creates some confusion in law enforcement communities; some agencies identify them as Eastern European traveling criminals. I include my personal experiences with problems associated in investigating these crimes. A qualitative research design was formulated for data collection in accordance with the standards of the methodology involving an ethnophenomenological study. Ten unstructured field interviews were conducted with veteran investigators identified as experts in the field of confidence crimes against the elderly, five retired and five currently active. The literature review includes criminal justice and criminal investigation, American Gypsy culture and history, and the field of adult education. The goal and final product is to improve and extend current literature in the field of adult continuing education and criminal justice. An important theme that emerged from this study is that the purposes and principles of adult education will benefit and support criminal justice education. This includes basic inservice training for officers and community education based on the idea that police officers should be taught adult education principles to prepare them to use a humanistic approach in instructing senior citizens about crime prevention. I believed there was a lack of education about the criminal element of this subculture. Most of the crimes it commits against the elderly are nonviolent and seldom make the news, and knowledge of the crime is realized only when the victim is a relative. Other themes that emerged from this study include the complexity of the criminal subculture organization, lack of basic recruit training for identifying and recording the crimes, need for inservice training for better crime scene investigation and current information on newly developed criminal methods, and need for community education of the elderly and their families. Finally, conclusions from the literature review and data collection resulted in recommendations that criminal justice educators draw on the humanistic approach, especially when training veteran police officers and detectives. Providing community education and the necessary tools to protect potential victims is paramount to the success of crime prevention

Effect of treatment on the hemodynamics system in systemic lupus erythematosus patients

Abstract   Systemic lupus erythematosus (SLE) is a rare autoimmune disease which is associated with inflammation and accelerated atherogenesis, as it's related to the endothelium activation process. Measurements of arterial stiffness and IMTc are a repeatable and noninvasive methods to estimate a CVD risk. We could assume that the outcome of the correct therapy, if applied in the early stage of the SLE, could prevent the consequences of vessel inflammation and retract endothelium lesions. Purpose The main objective of this study was to assess the common carotid artery thickness of the intima-media complex (IMTc), ankle-brachial index (ABI), and pulse wave velocity (PWV) in patients with SLE and compare the studied parameters between individuals treated with corticosteroids with patients with other medications or without treatment. Methods Consecutive patients with SLE were included prospectively to the study between X 2016 and XII 20120 in the 2nd Department of Cardiology of our Medical University. Patients with other connective tissue diseases and chronic inflammation were excluded from this study. Activity of SLE was measured by The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2K), with cut-off point at 6 points for active disease. Basic clinical data and cardiovascular (CVS) risk factors were gathered, each patient underwent the measurement of IMTc, ABI and cfPWV. All data were compared between groups treated or not treated with glicocorticosteroids (GCS). Results The study group consisted of 43 patients with SLE. Mean age was 57.4 years, 39 of the studied subjects were women, and 21 patients (48.84%) were treated with GCS. Mean duration of SLE time was 12.3 years, mean time of treatment with GCS was 5.3 years. On average the mean SLEDAI-2K value was 6.35±5.83 points and 18 patients (41.86%) had above 6 points. New-onset CV disease occurred in 6 patients (33.33%) treated with CGS and in 3 pts (25%) not treated with GCS (p=0.2546) Patients treated with GCS had lower values of ABI when compared to patients not treated with GCS (right ankle: 1.76 vs 1.86, p=0.047, left ankle: 1.63 vs 1.81, p=0.041) although the values were in the scope of standards. Similar situation occurred with the carotid femoral artery (cfPWV) (8.00 vs 8.83 m/s, p=0.032). However, the carotid radial artery PWV values were not significantly altered between groups (8.89 vs 9.61 m/s, p=0.12). The IMTc values were significantly higher in the GCS group (1.51 vs 1.13 mm, p&amp;lt;0.001). Statistically significant correlation with CVS risk factors was found for cfPWV (r=0.812, p=0.021). Conclusions Patients treated with GCS had lower cfPWV and ABI when compared to the group not treated with GCS. Further studies to establish the prognostic value of PWV among SLE patients are justified, as it could be superior to the IMTc measures at the early stage of vascular impairment, because PWV explores a greater range of vessels. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Medical University of Silesia in Katowice, Poland </jats:sec