LIN28A expression reduces sickling of cultured human erythrocytes

Induction of fetal hemoglobin (HbF) has therapeutic importance for patients with sickle cell disease (SCD) and the beta-thalassemias. It was recently reported that increased expression of LIN28 proteins or decreased expression of its target let-7 miRNAs enhances HbF levels in cultured primary human erythroblasts from adult healthy donors. Here LIN28A effects were studied further using erythrocytes cultured from peripheral blood progenitor cells of pediatric subjects with SCD. Transgenic expression of LIN28A was accomplished by lentiviral transduction in CD34(+) sickle cells cultivated ex vivo in serum-free medium. LIN28A over-expression (LIN28A-OE) increased HbF, reduced beta (sickle)-globin, and strongly suppressed all members of the let-7 family of miRNAs. LIN28A-OE did not affect erythroblast differentiation or prevent enucleation, but it significantly reduced or ameliorated the sickling morphologies of the enucleated erythrocytes

ATLAS liquid argon calorimeter front end electronics

The ATLAS detector has been designed for operation at CERN's Large Hadron Collider. ATLAS includes a complex system of liquid argon calorimeters. This paper describes the architecture and implementation of the system of custom front end electronics developed for the readout of the ATLAS liquid argon calorimeters

Design and implementation of the Front End Board for the readout of the ATLAS liquid argon calorimeters

The ATLAS detector has been designed for operation at CERN's Large Hadron Collider. ATLAS includes a complex system of liquid argon calorimeters. The electronics for amplifying, shaping, sampling, pipelining, and digitizing the calorimeter signals is implemented on the Front End Boards (FEBs). This paper describes the design, implementation and production of the FEBs and presents measurement results from testing performed at several stages during the production process

Socializing One Health: an innovative strategy to investigate social and behavioral risks of emerging viral threats

In an effort to strengthen global capacity to prevent, detect, and control infectious diseases in animals and people, the United States Agency for International Development’s (USAID) Emerging Pandemic Threats (EPT) PREDICT project funded development of regional, national, and local One Health capacities for early disease detection, rapid response, disease control, and risk reduction. From the outset, the EPT approach was inclusive of social science research methods designed to understand the contexts and behaviors of communities living and working at human-animal-environment interfaces considered high-risk for virus emergence. Using qualitative and quantitative approaches, PREDICT behavioral research aimed to identify and assess a range of socio-cultural behaviors that could be influential in zoonotic disease emergence, amplification, and transmission. This broad approach to behavioral risk characterization enabled us to identify and characterize human activities that could be linked to the transmission dynamics of new and emerging viruses. This paper provides a discussion of implementation of a social science approach within a zoonotic surveillance framework. We conducted in-depth ethnographic interviews and focus groups to better understand the individual- and community-level knowledge, attitudes, and practices that potentially put participants at risk for zoonotic disease transmission from the animals they live and work with, across 6 interface domains. When we asked highly-exposed individuals (ie. bushmeat hunters, wildlife or guano farmers) about the risk they perceived in their occupational activities, most did not perceive it to be risky, whether because it was normalized by years (or generations) of doing such an activity, or due to lack of information about potential risks. Integrating the social sciences allows investigations of the specific human activities that are hypothesized to drive disease emergence, amplification, and transmission, in order to better substantiate behavioral disease drivers, along with the social dimensions of infection and transmission dynamics. Understanding these dynamics is critical to achieving health security--the protection from threats to health-- which requires investments in both collective and individual health security. Involving behavioral sciences into zoonotic disease surveillance allowed us to push toward fuller community integration and engagement and toward dialogue and implementation of recommendations for disease prevention and improved health security

Talking the talk and walking the walk: an investigation of motor and verbal abilities and their interrelations at age three

Bold claims about interdependent progress across motor and verbal developmental domains shape scientific and popular perceptions of child development. Some people for instance assume that children who walk early will also talk early, while others claim that late talking may be explained or accompanied by superior motor development. Only few and mostly old investigations of the relations between verbal and motor abilities in early childhood exist. The current study assesses correlations between verbal and motor milestones, obtained via parental report, and a set of specific abilities measured with standardized tests (M-ABC-2 for motor, three WPSSI-III subtests for verbal). It also takes family and care characteristics as potential developmental predictors into consideration. A group of 38 German-speaking 3-year-olds (36-47 months) was tested. The homogeneous and high SES allowed us to explore interrelations between verbal and motor development in a setting void of social or economic disadvantages. We found no gender differences for any of the investigated variables. Participants demonstrated motor and verbal abilities that were slightly above the expected average in five out of six subtests. The ages at onset of talking and walking were positively and moderately correlated (r=.391). Performance scores for the information subtest of the WPSSI-III, a measure of general knowledge, correlated with picture naming scores (r=.399), an indication of expressive vocabulary, and receptive vocabulary scores (r=.641). Earlier onset of talking also tended to be related to higher picture naming scores (r=-.421). No correlations between any of the three motor subtests manual dexterity, aiming and catching, and balance, or across verbal and motor subtest performance were found. Duration and amount of daycare, maternal employment, and high vs. very high family income did not selectively predict motor or verbal abilities. In conclusion, this study finds no correlational relations between motor and verbal abilities and also no associations between the three different types of motor abilities tested. It thus provides systematic evidence that - in the absence of social or health risks – three-year-olds verbal abilities do not depend on their motor performance or vice versa

Clustering of health-related behavior patterns and demographics. Results from the population-based KORA S4/F4 cohort study.

Health behaviors are of great importance for public health. Previous research shows that health behaviors are clustered and do not occur by chance. The main objective of this study was to investigate and describe the clustering of alcohol consumption, nutrition, physical activity and smoking while also considering the influence of sex, age and education. Using data from the population-based KORA S4/F4 cohort study, latent class regression analysis was undertaken to identify different clusters of health behavior patterns. The clusters were described according to demographics. Furthermore, the clusters were described regarding health-related quality of life at baseline and at a 7 year follow-up. Based on a sample of 4,238 participants, three distinct classes were identified. One overall healthy class and two heterogeneous classes. Classes varied especially according to sex, indicating a healthier behavior pattern for females. No clear association between healthier classes and age, education or physical and mental health-related quality of life was found. This study strengthens the literature on the clustering of health behaviors and additionally describes the identified clusters in association with health-related quality of life. More research on associations between clustering of health behaviors and important clinical outcomes is needed