Structural and Non-Structural Alternatives for Accommodating Larger Floods at Dams

This paper provides an overview of structural and non-structural alternatives for accommodating larger floods at dams. The first two alternatives discussed, raising the height of the project and/or lowering the reservoir pool, can be used to prevent overtopping by increasing the available floodwater detention storage in the reservoir. Data gathered by an ASCE task committee survey on modifications that include increased storage by raising project height are summarized and discussed. The third alternative discussed, early warning systems, can provide a low cost alternative to structural modifications. Case studies for the warning systems at the Santee Cooper North Dam and the TVA Blue Ridge Dam are presented

The role of inflammation in age-related disease.

The National Institutes of Health (NIH) Geroscience Interest Group (GSIG) sponsored workshop, The Role of Inflammation inAge-Related Disease, was held September 6th-7th, 2012 in Bethesda, MD. It is now recognized that a mild pro-inflammatory state is correlated with the major degenerative diseases of the elderly. The focus of the workshop was to better understand the origins and consequences of this low level chronic inflammation in order to design appropriate interventional studies aimed at improving healthspan. Four sessions explored the intrinsic, environmental exposures and immune pathways by which chronic inflammation are generated, sustained, and lead to age-associated diseases. At the conclusion of the workshop recommendations to accelerate progress toward understanding the mechanistic bases of chronic disease were identified

Communicating serum chemical concentrations to study participants: follow up survey

<p>Abstract</p> <p>Background</p> <p>A considerable literature now supports the importance of effective communication with study participants, including how best to develop communication plans focusing on the uncertainty of health risks associated with particular environmental exposures. Strategies for communicating individual concentrations of environmental chemicals in human biological samples in the absence of clearly established safe or hazardous levels have been discussed from a conceptual basis and to a lesser extent from an empirical basis. We designed and evaluated an empirically based communication strategy for women of reproductive age who previously participated in a prospective study focusing on persistent environmental chemicals and reproductive outcomes.</p> <p>Methods</p> <p>A cohort of women followed from preconception through pregnancy or up to 12 menstrual cycles without pregnancy was given their individual serum concentrations for lead, dichloro-2,2-bis<it>p</it>-chlorophenyl ethylene, and select polychlorinated biphenyl congeners. Two versions of standardized letters were prepared depending upon women's exposure status, which was characterized as low or high. Letters included an introduction, individual concentrations, population reference values and guidance for minimizing future exposures. Participants were actively monitored for any questions or concerns following receipt of letters.</p> <p>Results</p> <p>Ninety-eight women were sent letters informing them of their individual concentrations to select study chemicals. None of the 89 (91%) participating women irrespective of exposure status contacted the research team with questions or concerns about communicated exposures despite an invitation to do so.</p> <p>Conclusions</p> <p>Our findings suggest that study participants can be informed about their individual serum concentrations without generating unnecessary concern.</p

Dichorionic twin trajectories: the NICHD Fetal Growth Studies

BACKGROUND: Systematic evaluation and estimation of growth trajectories in twins require ultrasound measurements across gestation, performed in controlled clinical settings. Currently there are few such data for contemporary populations. There is also controversy about whether twin fetal growth should be evaluated using the same benchmarks as singleton growth. OBJECTIVES: Our objective was to empirically define the trajectory of fetal growth in dichorionic twins using longitudinal two-dimensional ultrasonography and to compare the fetal growth trajectories for dichorionic twins with those based on a growth standard developed by our group for singletons. STUDY DESIGN: A prospective cohort of 171 women with twin gestations was recruited from eight U.S. sites from 2012 to 2013. After an initial sonogram at 11w0d–13w6d where dichorionicity was confirmed, women were randomized to one of two serial ultrasonology schedules. Growth curves and percentiles were estimated using linear mixed models with cubic splines. Percentiles were compared statistically at each gestational week between the twins and 1,731 singletons, after adjustment for maternal age, race/ethnicity, height, weight, parity, employment, marital status, insurance, income, education and infant sex. Linear mixed models were used to test for overall differences between the twin and singleton trajectories using likelihood ratio tests of interaction terms between spline mean structure terms and twin-singleton indicator variables. Singleton standards were weighted to correspond to the distribution of maternal race in twins. For those ultrasound measurements where there were significant global tests for differences between twins and singletons, we tested for week-specific differences using Wald tests computed at each gestational age. In a separate analysis, we evaluated the degree of reclassification in small for gestational age, defined as below the 10(th) percentile that would be introduced if fetal growth estimation for twins was based upon an unweighted singleton standard. RESULTS: Women underwent a median of 5 ultrasounds. The 50(th) percentile abdominal circumference and estimated fetal weight trajectories of twin fetuses diverged significantly beginning at 32 weeks, while biparietal diameter in twins was smaller from 34 through 36 weeks. There were no differences in head circumference or femur length. The mean head circumference/abdominal circumference ratio was progressively larger for twins compared with singletons beginning at 33 weeks, indicating a comparatively asymmetric growth pattern. At 35 weeks, the average gestational age at delivery for twins, the estimated fetal weights for the 10(th), 50(th) and 90(th) percentiles were 1960, 2376, and 2879 g for dichorionic twins and 2180, 2567, and 3022 g for the singletons. At 32 weeks, the initial week when the mean estimated fetal weight for twins was smaller than that of singletons, 34% of twins would be classified as small for gestational age using a singleton, non-Hispanic white standard. By 35 weeks, 38% of twins would be classified as small for gestational age. CONCLUSIONS: The comparatively asymmetric growth pattern in twin gestations, initially evident at 32 weeks, is consistent with the concept that the intrauterine environment becomes constrained in its ability to sustain growth in twin fetuses. Near term, nearly 40% of twins would be classified as small for gestational age based on a singleton growth standard

Homozygous Deletion of Six Olfactory Receptor Genes in a Subset of Individuals with Beta-Thalassemia

Progress in the functional studies of human olfactory receptors has been largely hampered by the lack of a reliable experimental model system. Although transgenic approaches in mice could characterize the function of individual olfactory receptors, the presence of over 300 functional genes in the human genome becomes a daunting task. Thus, the characterization of individuals with a genetic susceptibility to altered olfaction coupled with the absence of particular olfactory receptor genes will allow phenotype/genotype correlations and vindicate the function of specific olfactory receptors with their cognate ligands. We characterized a 118 kb β-globin deletion and found that its 3′ end breakpoint extends to the neighboring olfactory receptor region downstream of the β-globin gene cluster. This deletion encompasses six contiguous olfactory receptor genes (OR51V1, OR52Z1, OR51A1P, OR52A1, OR52A5, and OR52A4) all of which are expressed in the brain. Topology analysis of the encoded proteins from these olfactory receptor genes revealed that OR52Z1, OR52A1, OR52A5, and OR52A4 are predicted to be functional receptors as they display integral characteristics of G-proteins coupled receptors. Individuals homozygous for the 118 kb β-globin deletion are afflicted with β-thalassemia due to a homozygous deletion of the β-globin gene and have no alleles for the above mentioned olfactory receptors genes. This is the first example of a homozygous deletion of olfactory receptor genes in human. Although altered olfaction remains to be ascertained in these individuals, such a study can be carried out in β-thalassemia patients from Malaysia, Indonesia and the Philippines where this mutation is common. Furthermore, OR52A1 contains a γ-globin enhancer, which was previously shown to confer continuous expression of the fetal γ-globin genes. Thus, the hypothesis that β-thalassemia individuals, who are homozygous for the 118 kb deletion, may also have an exacerbation of their anemia due to the deletion of two copies of the γ-globin enhancer element is worthy of consideration

SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant