Predictive Associations Between Prenatal and Postnatal Risk Factors and Developmental and Temperamental Outcomes Among Infants in Foster Care

Infants detained for maltreatment present with a number of prenatal and perinatal risk factors, including prenatal exposure to substances, prematurity, low birth weight, birth complications, and prolonged hospital stay. These factors pose significant risk for a broad range of infant outcomes critically linked to later functioning, including cognitive, language, motor, socio-emotional, and temperamental development (Del Giudice, 2012; Singer et al., 2008). However, many infants exposed to prenatal risk also develop normatively, highlighting the need to better understand how the postnatal environment influences individual differences in response to prenatal risk. Importantly, prior to adoptive placement, infants placed in foster care often face unique stressors, including multiple foster placements and trial stays with birth families. Exposure to these pre-placement postnatal factors vary substantially across individuals, and they likely have unique and cumulative effects on developmental outcomes (Fisher et al., 2005; Waterman et al., 2013). Emerging evidence from normative samples suggests that prenatal and postnatal factors may interact to influence developmental outcomes, potentially through prenatal programming of infant responses to postnatal environments (Pluess & Belsky, 2011). These theoretical models have yet to be tested among infants in foster care, despite a need to better understand which prenatal and postnatal risk factors influence outcomes for these high-risk children. Thus, the present study aims to disentangle prenatal and postnatal risk factors to examine their unique and interactive associations with differentiated developmental outcomes (cognitive, language, motor, socioemotional) and early temperament among high-risk infants transitioning from foster care to adoption. Participants include 68 infants aged 0-28 months (race-ethnicity: 26% Hispanic, 14% African-American, 11% Caucasian, 1% Asian/Pacific Islander, 26% Mixed, 22% Unknown) referred for developmental assessment within two months of placement in adoptive homes. Prenatal/perinatal risk factors (prematurity, substance exposure, birth weight, birth complications, hospital stay) and postnatal risk factors (birth parent stay, age detained, number of placements, age at adoption) were coded from previous medical, DCFS, and court records. Infants were assessed using the Bayley Scales of Infant Development (BSID-III) to evaluate cognitive, motor (fine and gross), language (receptive and expressive), and socioemotional development. In addition, the primary adoptive parent completed the Infant/Toddler Temperament Questionnaire to measure temperament domains (e.g., sensitivity, reactivity, regularity). Preliminary correlations revealed that cognitive and motor development were most robustly associated with prenatal risk (i.e., prematurity, birth weight) and perinatal risk factors (i.e., birth complications, duration of hospital stay), whereas infant temperament domains were additionally linked to postnatal risk factors (i.e., birth parent placement, age detained, age of adoption, number of placements). Furthermore, differential associations between individual risk factors and outcomes were observed, suggesting there are likely unique risk factors predictive of different infant outcomes. Next, stepwise regressions will be employed to examine the independent, cumulative, and interactive associations between prenatal and postnatal risk factors on each developmental and temperamental outcome. Results will provide insight into the individual and cumulative effects of prenatal and preplacement postnatal risk factors for infants transitioning from foster care to adoption. Implications for key prevention and intervention targets among high-risk infants will be discussed

American Ginseng Modifies 137Cs-Induced DNA Damage and Oxidative Stress in Human Lymphocytes

The multifold bioactive medicinal properties of ginseng have been closely linked to its antioxidative ability, which is related to its ginsenoside content. Since the key mechanism of radiation-induced cell death and tissue damage is the generation of reactive oxygen species (ROS) that attack cellular DNA, this study focuses on the impact of a standardized North American ginseng extract (NAGE) on 137Cs-induced oxidative stress in human peripheral lymphocytes (PBL) obtained from 10 healthy individuals (6M/4F), 42.7 ± 4.6 years of age. At two different time points (0 h and 24 h before irradiation), we applied NAGE (250 - 1000 µg ml-1) to mononuclear cell cultures for cytokinesisblock micronuclei (MN) assay and determination of the state of oxidative stress in PBL. We found that at both time points, NAGE significantly reduced the MN yields in PBL after irradiation (1 and 2 Gy) in a concentration-dependent manner (P<0.001). Compared with radiation alone, the maximum reduction rate of MN yield were 51.1% and 49.1% after 1 Gy and 2 Gy exposures, respectively. We also found that before irradiation the presence of NAGE in the culture medium resulted in a significant increased intracellular total antioxidant capacity (TAC) in PBL. At both time points, the increment of 137Cs-induced MN yields in PBL was positively correlated with the increment of intracellular ROS production (R = 0.6 - 0.7, P = 0.002), but negatively correlated with the reduction of TAC levels (R = -0.4 - 0.5, P = 0.02 - 0.004). However, the presence of NAGE in the culture medium significantly increased the TAC levels, while concomitantly decreasing both ROS production and MN yields in PBL (P<0.001). Our findings that NAGE is effective in protecting human PBL against radiation-induced oxidative stress should encourage further in vivo study of dietary supplementation with NAGE as an effective natural radiation countermeasure. Originally published Open Nuclear Medicine Journal Vol 1 No. 1, 2009

Greatest Potential, Greatest Need: Soaring Beyond Expectations

As an introduction, this article provides context for consideration of a special population of gifted children, the highly gifted. Justification for specialized service for this population, recommendations regarding various content area applications, and rationales for these students\u27 need to find a place of belonging are examined and discussed. Special considerations are given to the interactions between cognitive levels and affective intensities. The core materials for this volume originated with selected presentations from Greatest Potential, Greatest Need: Soaring Beyond Expectations- a Conference on Highly Gifted Children hosted by the Institute for the Development of Gifted Education, Morgridge College of Education, University of Denver, on October 7 and 8, 2009. Highly gifted children are as different from gifted children as gifted children are from typical learners. And, as a reflection of their difference from the norm, they are highly unique individuals as well. The concept underlying many of these articles is based on Annemarie Roeper\u27s (1982) definition of giftedness: Giftedness is a greater awareness, a greater sensitivity, and a greater ability to understand and transform perceptions into intellectual and emotional experiences (as cited by Silverman, 2011, p. 20), and expanded upon by Linda Silverman: The highly gifted have a different worldview (p. 10). Recognition of these differences and subsequent needs is not only essential to serve this population, but also to create environments that allow them to thrive. Those of us working with these children have no greater opportunity to impact the future than to care for and cherish these unique individuals.https://digitalcommons.du.edu/perspectivesingifteded/1006/thumbnail.jp

Radioprotective Effect of American Ginseng on Human Lymphocytes at 90 Minutes Post-irradiation: A Study of 40 Cases

Backgroundâ Ionizing radiation (IR) initiates intracellular oxidative stress through enhanced formation of reactive oxygen species (ROS) that attack DNA leading to cell death. As the diversity of IR applied in medicine, agriculture, industry, and the growing threats of global terrorism, the acquisition of radioprotectors is an urgent need for the nation. However, the applicability of radioprotectors currently under investigation is limited due to their inherent toxicity. Objectiveâ This study investigated the effect of a standardized North American ginseng extract (NAGE, total ginsenoside content: 11.7%) on DNA damage in human lymphocytes at 90 min postirradiation. Designâ With the application of NAGE (250 â 1000 μg mlâ 1) at 90 min post-irradiation (1 and 2 Gy), DNA damage in lymphocytes obtained from 40 healthy individuals was evaluated by cytokinesis-block micronucleus (CBMN) assay. Similar experiments were also performed in lymphocytes treated with WR-1065 (1 mM or 3mM). In addition, before and after irradiation, lymphocytes obtained from 10 individuals were measured for their total antioxidant capacity (TAC) and the reactive oxygen species (ROS). Resultsâ The significant effect of NAGE against 137Cs-induced MN in lymphocytes is concentration-dependent. NAGE (750 μg mlâ 1) reduced MN yield by 50.7% after 1 Gy and 35.9% after 2 Gy exposures, respectively; these results were comparable to that of WR-1065. Further, we also found that NAGE reduces MN yield and ROS but increases TAC in lymphocytes. Conclusionsâ Our results suggest that NAGE is a relatively non-toxic natural compound that holds radioprotective potential in human lymphocytes even when applied at 90 min post-irradiation. One of the radioprotective mechanisms may be mediated through the scavenging of free radicals and enhancement of the intracellular TAC. Originally published Journal of Alternative and Complementary Medicine Vol. 16, No. 5 2010

Immunization with GP1 but Not Core-like Particles Displaying Isolated Receptor-Binding Epitopes Elicits Virus-Neutralizing Antibodies against Junín Virus

New World arenaviruses are rodent-transmitted viruses and include a number of pathogens that are responsible for causing severe human disease. This includes Junín virus (JUNV), which is the causative agent of Argentine hemorrhagic fever. The wild nature and mobility of the rodent reservoir host makes it difficult to control the disease, and currently passive immunization with high-titer neutralizing antibody-containing plasma from convalescent patients is the only specific therapy. However, dwindling supplies of naturally available convalescent plasma, and challenges in developing similar resources for other closely related viruses, have made the development of alternative antibody-based therapeutic approaches of critical importance. In this study, we sought to induce a neutralizing antibody response in rabbits against the receptor-binding subunit of the viral glycoprotein, GP1, and the specific peptide sequences in GP1 involved in cellular receptor contacts. While these specific receptor-interacting peptides did not efficiently induce the production of neutralizing antibodies when delivered as a particulate antigen (as part of hepatitis B virus core-like particles), we showed that recombinant JUNV GP1 purified from transfected mammalian cells induced virus-neutralizing antibodies at high titers in rabbits. Further, neutralization was observed across a range of unrelated JUNV strains, a feature that is critical for effectiveness in the field. These results underscore the potential of GP1 alone to induce a potent neutralizing antibody response and highlight the importance of epitope presentation. In addition, effective virus neutralization by rabbit antibodies supports the potential applicability of this species for the future development of immunotherapeutics (e.g., based on humanized monoclonal antibodies). Such information can be applied in the design of vaccines and immunogens for both prevention and specific therapies against this and likely also other closely related pathogenic New World arenaviruses.Fil: Roman Sosa, Gleyder. Ulm University Hospital; AlemaniaFil: Leske, Anne. Friedrich-Loeffler-Institut; AlemaniaFil: Ficht, Xenia. Ulm University Hospital; AlemaniaFil: Dau, Tung Huy. Friedrich-Loeffler-Institut; AlemaniaFil: Holzerland, Julia. Friedrich-Loeffler-Institut; AlemaniaFil: Hoenen, Thomas. Friedrich-Loeffler-Institut; AlemaniaFil: Beer, Martin. Friedrich-Loeffler-Institut; AlemaniaFil: Kammerer, Robert. Friedrich-Loeffler-Institut; AlemaniaFil: Schirmbeck, Reinhold. Friedrich-Loeffler-Institut; AlemaniaFil: Rey, Felix A.. Friedrich-Loeffler-Institut; AlemaniaFil: Cordo, Sandra Myriam. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Groseth, Allison. Friedrich-Loeffler-Institut; Alemani

Body circumferences: clinical implications emerging from a new geometric model

<p>Abstract</p> <p>Background</p> <p>Body volume expands with the positive energy balance associated with the development of adult human obesity and this "growth" is captured by two widely used clinical metrics, waist circumference and body mass index (BMI). Empirical correlations between circumferences, BMI, and related body compartments are frequently reported but fail to provide an important common conceptual foundation that can be related to key clinical observations. A two-phase program was designed to fill this important gap: a geometric model linking body volume with circumferences and BMI was developed and validated in cross-sectional cohorts; and the model was applied to the evaluation of longitudinally monitored subjects during periods of voluntary weight loss. Concepts emerging from the developed model were then used to examine the relations between the evaluated clinical measures and body composition.</p> <p>Methods</p> <p>Two groups of healthy adults (n = 494 and 1499) were included in the cross-sectional model development/testing phase and subjects in two previous weight loss studies were included in the longitudinal model evaluation phase. Five circumferences (arm, waist, hip, thigh, and calf; average of sum, C), height (H), BMI, body volume (V; underwater weighing), and the volumes of major body compartments (whole-body magnetic resonance imaging) were measured.</p> <p>Results</p> <p>The evaluation of a humanoid geometric model based a cylinder confirmed that V derived from C and H was highly correlated with measured V [R²both males and females, 0.97; p < 0.001). Developed allometric models confirmed model predictions that C and BMI (represented as V/H) are directly linked as, C = (V/H)^0.5. The scaling of individual circumferences to V/H varied, with waist the highest (V/H^~0.6) and calf the lowest (V/H^~0.3), indicating that the largest and smallest between-subject "growth" with greater body volume occurs in the abdominal area and lower extremities, respectively. A stepwise linear regression model including all five circumferences²showed that each contributed independently to V/H. These cross-sectional observations were generally confirmed by analysis of the two longitudinal weight loss studies. The scaling of circumference ratios (e.g., waist/hip) to V/H conformed to models developed on the scaling of individual circumferences to V/H, indicating their relations to BMI are predictable <it>a priori</it>. Waist, hip, and arm/calf circumferences had the highest associations with whole-body visceral adipose tissue, subcutaneous adipose tissue, and skeletal muscle volumes, respectively.</p> <p>Conclusion</p> <p>These observations provide a simple geometric model relating circumferences with body size and composition, introduce a conceptual foundation explaining previous empirical observations, and reveal new clinical insights.</p

Measurement of the Atmospheric Muon Spectrum from 20 to 3000 GeV

The absolute muon flux between 20 GeV and 3000 GeV is measured with the L3 magnetic muon spectrometer for zenith angles ranging from 0 degree to 58 degree. Due to the large exposure of about 150 m2 sr d, and the excellent momentum resolution of the L3 muon chambers, a precision of 2.3 % at 150 GeV in the vertical direction is achieved. The ratio of positive to negative muons is studied between 20 GeV and 500 GeV, and the average vertical muon charge ratio is found to be 1.285 +- 0.003 (stat.) +- 0.019 (syst.).Comment: Total 32 pages, 9Figure

Enabling precision manufacturing of active pharmaceutical ingredients: workflow for seeded cooling continuous crystallisations

Continuous manufacturing is widely used for the production of commodity products. Currently, it is attracting increasing interest from the pharmaceutical industry and regulatory agencies as a means to provide a consistent supply of medicines. Crystallisation is a key operation in the isolation of the majority of pharmaceuticals and has been demonstrated in a continuous manner on a number of compounds using a range of processing technologies and scales. Whilst basic design principles for crystallisations and continuous processes are known, applying these in the context of rapid pharmaceutical process development with the associated constraints of speed to market and limited material availability is challenging. A systematic approach for continuous crystallisation process design is required to avoid the risk that decisions made on one aspect of the process conspire to make a later development step or steps, either for crystallisation or another unit operation, more difficult. In response to this industry challenge, an innovative system-wide approach to decision making has been developed to support rapid, systematic, and efficient continuous seeded cooling crystallisation process design. For continuous crystallisation, the goal is to develop and operate a robust, consistent process with tight control of particle attributes. Here, an innovative system-based workflow is presented that addresses this challenge. The aim, methodology, key decisions and output at each at stage are defined and a case study is presented demonstrating the successful application of the workflow for the rapid design of processes to produce kilo quantities of product with distinct, specified attributes suited to the pharmaceutical development environment. This work concludes with a vision for future applications of workflows in continuous manufacturing development to achieve rapid performance based design of pharmaceuticals