Whole-exome sequencing reveals a C-terminal germline variant in CEBPA-associated acute myeloid leukemia: 45-year follow-up of a large family.

Familial acute myeloid leukemia is rare and linked to germline mutations in RUNX1, GATA2 or CCAAT/enhancer binding protein-α (CEBPA). We re-evaluated a large family with acute myeloid leukemia originally seen at NIH in 1969. We utilized whole-exome sequencing to study this family, and conducted in silico bioinformatics analysis, protein structural modeling and laboratory experiments to assess the impact of the identified CEBPA Q311P mutation. Unlike most previously identified germline mutations in CEBPA, which were N-terminal frameshift mutations, we identified a novel Q311P variant that was located in the C-terminal bZip domain of C/EBPα. Protein structural modeling suggested that the Q311P mutation alters the ability of the CEBPA dimer to bind DNA. Electrophoretic mobility shift assays showed that the Q311P mutant had attenuated binding to DNA, as predicted by the protein modeling. Consistent with these findings, we found that the Q311P mutation has reduced transactivation, consistent with a loss-of-function mutation. From 45 years of follow-up, we observed incomplete penetrance (46%) of CEBPA Q311P. This study of a large multi-generational pedigree reveals that a germline mutation in the C-terminal bZip domain can alter the ability of C/EBP-α to bind DNA and reduces transactivation, leading to acute myeloid leukemia.

Gender-Specific Associations between Circulating T-Cadherin and High Molecular Weight-Adiponectin in Patients with Stable Coronary Artery Disease.

Close relationships exist between presence of adiponectin (APN) within vascular tissue and expression of T-cadherin (T-cad) on vascular cells. APN and T-cad are also present in the circulation but here their relationships are unknown. This study investigates associations between circulating levels of high molecular weight APN (HMW-APN) and T-cad in a population comprising 66 women and 181 men with angiographically proven stable coronary artery disease (CAD). Plasma HMW-APN and T-cad were measured by ELISA and analysed for associations with baseline clinical characteristics and with each other. In multivariable analysis BMI and HDL were independently associated with HMW-APN in both genders, while diabetes and extent of coronary stenosis were independently associated with T-cad in males only. Regression analysis showed no significant association between HMW-APN and T-cad in the overall study population. However, there was a negative association between HMW-APN and T-cad (P=0.037) in a subgroup of young men (age <60 years, had no diabetes and no or 1-vessel CAD) which persisted after multivariable analysis with adjustment for all potentially influential variables (P=0.021). In the corresponding subgroup of women there was a positive association between HMW-APN and T-cad (P=0.013) which disappeared after adjustment for HDL. After exclusion of the young men, a positive association (P=0.008) between HMW-APN and T-cad was found for the remaining participants of the overall population which disappeared after adjustment for HDL and BMI. The existence of opposing correlations between circulating HMW-APN and T-cad in male and female patient populations underscores the necessity to consider gender as a confounding variable when evaluating biomarker potentials of APN and T-cad.

Risk Factors for Intracranial Haemorrhage in Accidents Associated with the Shower or Bathtub

BACKGROUND There has been little research on bathroom accidents. It is unknown whether the shower or bathtub are connected with special dangers in different age groups or whether there are specific risk factors for adverse outcomes. METHODS This cross-sectional analysis included all direct admissions to the Emergency Department at the Inselspital Bern, Switzerland from 1 January 2000 to 28 February 2014 after accidents associated with the bathtub or shower. Time, age, location, mechanism and diagnosis were assessed and special risk factors were examined. Patient groups with and without intracranial bleeding were compared with the Mann-Whitney U test.The association of risk factors with intracranial bleeding was investigated using univariate analysis with Fisher's exact test or logistic regression. The effects of different variables on cerebral bleeding were analysed by multivariate logistic regression. RESULTS Two hundred and eighty (280) patients with accidents associated with the bathtub or shower were included in our study. Two hundred and thirty-five (235) patients suffered direct trauma by hitting an object (83.9%) and traumatic brain injury (TBI) was detected in 28 patients (10%). Eight (8) of the 27 patients with mild traumatic brain injuries (GCS 13-15), (29.6%) exhibited intracranial haemorrhage. All patients with intracranial haemorrhage were older than 48 years and needed in-hospital treatment. Patients with intracranial haemorrhage were significantly older and had higher haemoglobin levels than the control group with TBI but without intracranial bleeding (p<0.05 for both).In univariate analysis, we found that intracranial haemorrhage in patients with TBI was associated with direct trauma in general and with age (both p<0.05), but not with the mechanism of the fall, its location (shower or bathtub) or the gender of the patient. Multivariate logistic regression analysis identified only age as a risk factor for cerebral bleeding (p<0.05; OR 1.09 (CI 1.01;1.171)). CONCLUSION In patients with ED admissions associated with the bathtub or shower direct trauma and age are risk factors for intracranial haemorrhage. Additional effort in prevention should be considered, especially in the elderly.

Selenium isotope analysis by N-TIMS: Potential and challenges

The isotope composition of selenium (Se) can provide important constraints on biological, geochemical, and cosmochemical processes taking place in different reservoirs on Earth and during planet formation. To provide precise qualitative and quantitative information on these processes, accurate and highly precise isotope data need to be obtained. The currently applied ICP-MS methods for Se isotope measurements are compromised by the necessity to perform a large number of interference corrections. Differences in these correction methods can lead to discrepancies in published Se isotope values of rock standards which are significantly higher than the acclaimed precision. An independent analytical approach applying a double spike (DS) and state-of-the-art TIMS may yield better precision due to its smaller number of interferences and could test the accuracy of data obtained by ICP-MS approaches. This study shows that the precision of Se isotope measurements performed with two different Thermo Scientific™ Triton™ Plus TIMS is distinctly deteriorated by about ±1‰ (2 s.d.) due to δ80/78Se by a memory Se signal of up to several millivolts and additional minor residual mass bias which could not be corrected for with the common isotope fractionation laws. This memory Se has a variable isotope composition with a DS fraction of up to 20% and accumulates with increasing number of measurements. Thus it represents an accumulation of Se from previous Se measurements with a potential addition from a sample or machine blank. Several cleaning techniques of the MS parts were tried to decrease the memory signal, but were not sufficient to perform precise Se isotope analysis. If these serious memory problems can be overcome in the future, the precision and accuracy of Se isotope analysis with TIMS should be significantly better than those of the current ICP-MS approaches.

Clinical factors associated with growth and mortality of pediatric patients on HAART at Mulago PIDC, Uganda, 2003--2006

The global social and economic burden of HIV/AIDS is great, with over forty million people reported to be living with HIV/AIDS at the end of 2005; two million of these are children from birth to 15 years of age. Antiretroviral therapy has been shown to improve growth and survival of HIV-infected individuals. The purpose of this study is to describe a cohort of HIV-infected pediatric patients and assess the association between clinical factors, with growth and mortality outcomes. ^ This was a historical cohort study. Medical records of infants and children receiving HIV care at Mulago Pediatric Infectious Disease Clinic (PIDC) in Uganda between July 2003 and March 2006 were analyzed. Height and weight measurements were age and sex standardized to Centers for Disease Control and prevention (CDC) 2000 reference. Descriptive and logistic regression analyses were performed to identify covariates associated with risk of stunting or being underweight, and mortality. Longitudinal regression analysis with a mixed model using autoregressive covariance structure was used to compare change in height and weight before and after initiation of highly active antiretroviral therapy (HAART). ^ The study population was comprised of 1059 patients 0-20 years of age, the majority of whom were aged thirteen years and below (74.6%). Mean height-for-age before initiation of HAART was in the 10th percentile, mean weight-for-age was in the 8th percentile, and the mean weight-for-height was in the 23rd percentile. Initiation of HAART resulted in improvement in both the mean standardized weight-for-age Z score and weight-for-age percentiles (p <0.001). Baseline age, and weight-for-age Z score were associated with stunting (p <0.001). A negative weight-for-age Z score was associated with stunting (OR 4.60, CI 3.04-5.49). Risk of death decreased from 84% in the >2-8 years age category to 21% in the >13 years age category respectively, compared to the 0-2 years of age (p <0.05). ^ This pediatric population gained weight significantly more rapidly than height after starting HAART. A low weight-for-age Z score was associated with poor survival in children. These findings suggest that age, weight, and height measurements be monitored closely at Mulago PIDC. ^

Risk factors for encephalitis and death from West Nile virus infection: An analysis of hospitalized cases in Houston, Texas from 2002--2008

We conducted a nested case-control study to determine the significant risk factors for developing encephalitis from West Nile virus (WNV) infection. The purpose of this research project was to expand the previously published Houston study of 2002–2004 patients to include data on Houston patients from four additional years (2005–2008) to determine if there were any differences in risk factors shown to be associated with developing the more severe outcomes of WNV infection, encephalitis and death, by having this larger sample size. A re-analysis of the risk factors for encephalitis and death was conducted on all of the patients from 2002–2008 and was the focus of this proposed research. This analysis allowed for the determination to be made that there are differences in the outcome in the risk factors for encephalitis and death with an increased sample size. Retrospective medical chart reviews were completed for the 265 confirmed WNV hospitalized patients; 153 patients had encephalitis (WNE), 112 had either viral syndrome with fever (WNF) or meningitis (WNM); a total of 22 patients died. Univariate logistic regression analyses on demographic, comorbidities, and social risk factors was conducted in a similar manner as in the previously conducted study to determine the risk factors for developing encephalitis from WNV. A multivariate model was developed by using model building strategies for the multivariate logistic regression analysis. The hypothesis of this study was that there would be additional risk factors shown to be significant with the increase in sample size of the dataset. This analysis with a greater sample size and increased power supports the hypothesis in that there were additional risk factors shown to be statistically associated with the more severe outcomes of WNV infection (WNE or death). Based on univariate logistic regression results, these data showed that even though age of 20–44 years was statistically significant as a protecting effect for developing WNE in the original study, the expanded sample lacked significance. This study showed a significant WNE risk factor to be chronic alcohol abuse, when it was not significant in the original analysis. Other WNE risk factors identified in this analysis that showed to be significant but were not significant in the original analysis were cancer not in remission > 5 years, history of stroke, and chronic renal disease. When comparing the two analyses with death as an outcome, two risk factors that were shown to be significant in the original analysis but not in the expanded dataset analysis were diabetes mellitus and immunosuppression. Three risk factors shown to be significant in this expanded analysis but were not significant in the original study were illicit drug use, heroin or opiate use, and injection drug use. However, with the multiple logistic regression models, the same independent risk factors for developing encephalitis of age and history of hypertension including drug induced hypertension were consistent in both studies.^

Internet sex among non-gay identifying men who have sex with men

The aim of this study was to examine the role of the Internet in Internal Homonegativity (IH) among Non gay identifying men who have sex with men (NGI-MSM). This study at University of Texas School of Public Health (UTSPH) had a mixed method research design and consisted of men 18 years of age and older who were residents of the US and Canada. The data were collected using an online survey called 'Men's Sexual Health Survey' which was developed in collaboration with Boston University School of Public Health and Denver Public Health. These surveys were administered in English, which took 30-minutes to complete, and were placed on gay oriented websites and chat rooms. 141 participants were presented with the module relating to IH. A Principal Component Analysis with varimax rotation on the nine questions that asked the participants about their feelings about gay men produced three factors of IH identified as (1) public identification as gay; (2) perception of stigma associated with being gay; and (3) social comfort with gay men. The factors significantly correlated with age, grade completed in school, income, openness about being gay and socializing with gay people, meeting partners online, dating on the Internet, attitude toward condom usage, alcohol and drug use before sex and having unprotected sex with Internet partners. These findings point toward the role of the Internet in determining IH and sexual behavior. Despite the risks, the Internet's popularity and outreach in NGI-MSM makes it an effective medium to spread public health programs.^

Behavioral decision making and the levels of change: An application of the transtheoretical model to prenatal smoking in low -income women

Despite continued research and public health efforts to reduce smoking during pregnancy, prenatal cessation rates in the United States have decreased and the incidence of low birth weight has increased from 1985 to 1991. Lower socioeconomic status women who are at increased risk for poor pregnancy outcomes may be resistant to current intervention efforts during pregnancy. The purpose of this dissertation was to investigate the determinants of continued smoking and quitting among low-income pregnant women.^ Using data from cross-sectional surveys of 323 low-income pregnant smokers, the first study developed and tested measures of the pros and cons of smoking during pregnancy. The original decisional balance measure for smoking was compared with a new measure that added items thought to be more salient to the target population. Confirmatory factor analysis using structural equation modeling showed neither the original nor new measure fit the data adequately. Using behavioral science theory, content from interviews with the population, and statistical evidence, two 7-item scales representing the pros and cons were developed from a portion (n = 215) of the sample and successfully cross-validated on the remainder of the sample (n = 108). Logistic regression found only pros were significantly associated with continued smoking. In a discriminant function analysis, stage of change was significantly associated with pros and cons of smoking.^ The second study examined the structural relationships between psychosocial constructs representing some of the levels of and the pros and cons of smoking. The cross-sectional design mandates that statements made regarding prediction do not prove causation or directionality from the data or methods analysis. Structural equation modeling found the following: more stressors and family criticism were significantly more predictive of negative affect than social support; a bi-directional relationship was found between negative affect and current nicotine addiction; and negative affect, addiction, stressors, and family criticism were significant predictors of pros of smoking.^ The findings imply reversing the trend of decreasing smoking cessation during pregnancy may require supplementing current interventions for this population of pregnant smokers with programs addressing nicotine addiction, negative affect, and other psychosocial factors such as family functioning and stressors. ^

El análisis regional en la Argentina : Enfoque teórico-metodológico y aportes para su profundización

El artículo presenta los principales núcleos del enfoque de análisis regional en la Argentina, realizando distintos aportes a su desarrollo sobre las dinámicas de acumulación y hegemonía. En ese sentido, retomamos a autores como Rofman, de Jong y Levín, para comprender la relación entre territorio y sociedad. Partimos del planteo de construcción de conocimiento sintético y holístico, tratando de integrar las distintas escalas del análisis espacial con sus particularidades y sus interpenetraciones. La relación espacio/modo de producción nos lleva a la pregunta por las transformaciones orgánicas del capital como relación social y, así, al estudio del proceso de reproducción ampliada del capital a partir de conceptos como el de régimen y modelo de acumulación, a diferentes escalas, alcances y niveles de abstracción. Vemos las relaciones de fuerzas a nivel internacional a la luz de la disputa por distintos monopolios estratégicos, que señala Amín, y del lugar de las corporaciones transnacionales como agentes centrales de los regímenes de acumulación actual. En ese punto, continuamos desarrollando el plan de análisis de relaciones de fuerzas gramsciano, desde su nivel estructural hasta el momento de la hegemonía. De esta manera, la construcción del territorio dentro de una formación social nacional lleva a indagar la dinámica del proceso productivo, sus agentes, fracciones y clases, así como el rol del Estado y de la disputa entre distintos proyectos societarios. Estas dimensiones aparecen, asimismo, conjugadas, en una escala menor, en el análisis de los subsistemas espaciales de acumulación y de los circuitos productivos regionales que los constituyen. La explicitación de diversas claves teórico-metodológicas aparece atravesada por el debate en torno a repensar la planificación del espacio social, preguntándonos ¿qué territorio para qué sociedad?

Efectos de un programa de actividad física en escolares

Objetivos: Comprobar el efecto que tiene sobre el alumnado de Educación Primaria un programa de actividad física durante los recreos escolares mediante juegos pre-deportivos, en la composición corporal y en la condición física de los mismos. Metodología: Se realizó un análisis de las diferencias antes-después de muestras independientes de las pruebas de condición física y de las medidas antropométricas (grupo control y experimental), así como el valor de p de los contrastes, realizado mediante un análisis estadístico con el programa IBM SPSS 20.0. Aplicación a 54 alumnos y alumnas de Educación Primaria, de entre 9 y 11 años. Instrumentos: test de los 500 metros (resistencia); test de lanzamiento de balón medicinal (fuerza tren superior); test del salto horizontal (fuerza tren inferior); test de los 50 metros (velocidad); test de flexión profunda de tronco (flexibilidad). Resultados: Un estilo de vida activo, practicando actividad física diaria, se relaciona con mejoras en la condición física y en la composición corporal de sus practicantes. Conclusiones: Un programa de actividad física realizado en los recreos escolares con una duración de 30 minutos durante tres días a la semana, produce mejoras en los valores del IMC y la condición física de quien lo practica.

El análisis regional en la Argentina : Enfoque teórico-metodológico y aportes para su profundización

El artículo presenta los principales núcleos del enfoque de análisis regional en la Argentina, realizando distintos aportes a su desarrollo sobre las dinámicas de acumulación y hegemonía. En ese sentido, retomamos a autores como Rofman, de Jong y Levín, para comprender la relación entre territorio y sociedad. Partimos del planteo de construcción de conocimiento sintético y holístico, tratando de integrar las distintas escalas del análisis espacial con sus particularidades y sus interpenetraciones. La relación espacio/modo de producción nos lleva a la pregunta por las transformaciones orgánicas del capital como relación social y, así, al estudio del proceso de reproducción ampliada del capital a partir de conceptos como el de régimen y modelo de acumulación, a diferentes escalas, alcances y niveles de abstracción. Vemos las relaciones de fuerzas a nivel internacional a la luz de la disputa por distintos monopolios estratégicos, que señala Amín, y del lugar de las corporaciones transnacionales como agentes centrales de los regímenes de acumulación actual. En ese punto, continuamos desarrollando el plan de análisis de relaciones de fuerzas gramsciano, desde su nivel estructural hasta el momento de la hegemonía. De esta manera, la construcción del territorio dentro de una formación social nacional lleva a indagar la dinámica del proceso productivo, sus agentes, fracciones y clases, así como el rol del Estado y de la disputa entre distintos proyectos societarios. Estas dimensiones aparecen, asimismo, conjugadas, en una escala menor, en el análisis de los subsistemas espaciales de acumulación y de los circuitos productivos regionales que los constituyen. La explicitación de diversas claves teórico-metodológicas aparece atravesada por el debate en torno a repensar la planificación del espacio social, preguntándonos ¿qué territorio para qué sociedad?

Efectos de un programa de actividad física en escolares

Objetivos: Comprobar el efecto que tiene sobre el alumnado de Educación Primaria un programa de actividad física durante los recreos escolares mediante juegos pre-deportivos, en la composición corporal y en la condición física de los mismos. Metodología: Se realizó un análisis de las diferencias antes-después de muestras independientes de las pruebas de condición física y de las medidas antropométricas (grupo control y experimental), así como el valor de p de los contrastes, realizado mediante un análisis estadístico con el programa IBM SPSS 20.0. Aplicación a 54 alumnos y alumnas de Educación Primaria, de entre 9 y 11 años. Instrumentos: test de los 500 metros (resistencia); test de lanzamiento de balón medicinal (fuerza tren superior); test del salto horizontal (fuerza tren inferior); test de los 50 metros (velocidad); test de flexión profunda de tronco (flexibilidad). Resultados: Un estilo de vida activo, practicando actividad física diaria, se relaciona con mejoras en la condición física y en la composición corporal de sus practicantes. Conclusiones: Un programa de actividad física realizado en los recreos escolares con una duración de 30 minutos durante tres días a la semana, produce mejoras en los valores del IMC y la condición física de quien lo practica.

Efectos de un programa de actividad física en escolares

Objetivos: Comprobar el efecto que tiene sobre el alumnado de Educación Primaria un programa de actividad física durante los recreos escolares mediante juegos pre-deportivos, en la composición corporal y en la condición física de los mismos. Metodología: Se realizó un análisis de las diferencias antes-después de muestras independientes de las pruebas de condición física y de las medidas antropométricas (grupo control y experimental), así como el valor de p de los contrastes, realizado mediante un análisis estadístico con el programa IBM SPSS 20.0. Aplicación a 54 alumnos y alumnas de Educación Primaria, de entre 9 y 11 años. Instrumentos: test de los 500 metros (resistencia); test de lanzamiento de balón medicinal (fuerza tren superior); test del salto horizontal (fuerza tren inferior); test de los 50 metros (velocidad); test de flexión profunda de tronco (flexibilidad). Resultados: Un estilo de vida activo, practicando actividad física diaria, se relaciona con mejoras en la condición física y en la composición corporal de sus practicantes. Conclusiones: Un programa de actividad física realizado en los recreos escolares con una duración de 30 minutos durante tres días a la semana, produce mejoras en los valores del IMC y la condición física de quien lo practica.

Results of bulk sediment X-ray diffraction analysis and quantification of mineral phases based on the RockJock and on the QUAX quantitative analysis

We have performed quantitative X-ray diffraction (qXRD) analysis of 157 grab or core-top samples from the western Nordic Seas between (WNS) ~57°-75°N and 5° to 45° W. The RockJock Vs6 analysis includes non-clay (20) and clay (10) mineral species in the <2 mm size fraction that sum to 100 weight %. The data matrix was reduced to 9 and 6 variables respectively by excluding minerals with low weight% and by grouping into larger groups, such as the alkali and plagioclase feldspars. Because of its potential dual origins calcite was placed outside of the sum. We initially hypothesized that a combination of regional bedrock outcrops and transport associated with drift-ice, meltwater plumes, and bottom currents would result in 6 clusters defined by "similar" mineral compositions. The hypothesis was tested by use of a fuzzy k-mean clustering algorithm and key minerals were identified by step-wise Discriminant Function Analysis. Key minerals in defining the clusters include quartz, pyroxene, muscovite, and amphibole. With 5 clusters, 87.5% of the observations are correctly classified. The geographic distributions of the five k-mean clusters compares reasonably well with the original hypothesis. The close spatial relationship between bedrock geology and discrete cluster membership stresses the importance of this variable at both the WNS-scale and at a more local scale in NE Greenland.

El análisis regional en la Argentina : Enfoque teórico-metodológico y aportes para su profundización

El artículo presenta los principales núcleos del enfoque de análisis regional en la Argentina, realizando distintos aportes a su desarrollo sobre las dinámicas de acumulación y hegemonía. En ese sentido, retomamos a autores como Rofman, de Jong y Levín, para comprender la relación entre territorio y sociedad. Partimos del planteo de construcción de conocimiento sintético y holístico, tratando de integrar las distintas escalas del análisis espacial con sus particularidades y sus interpenetraciones. La relación espacio/modo de producción nos lleva a la pregunta por las transformaciones orgánicas del capital como relación social y, así, al estudio del proceso de reproducción ampliada del capital a partir de conceptos como el de régimen y modelo de acumulación, a diferentes escalas, alcances y niveles de abstracción. Vemos las relaciones de fuerzas a nivel internacional a la luz de la disputa por distintos monopolios estratégicos, que señala Amín, y del lugar de las corporaciones transnacionales como agentes centrales de los regímenes de acumulación actual. En ese punto, continuamos desarrollando el plan de análisis de relaciones de fuerzas gramsciano, desde su nivel estructural hasta el momento de la hegemonía. De esta manera, la construcción del territorio dentro de una formación social nacional lleva a indagar la dinámica del proceso productivo, sus agentes, fracciones y clases, así como el rol del Estado y de la disputa entre distintos proyectos societarios. Estas dimensiones aparecen, asimismo, conjugadas, en una escala menor, en el análisis de los subsistemas espaciales de acumulación y de los circuitos productivos regionales que los constituyen. La explicitación de diversas claves teórico-metodológicas aparece atravesada por el debate en torno a repensar la planificación del espacio social, preguntándonos ¿qué territorio para qué sociedad?