Residential radon-222 exposure and lung cancer: exposure assessment methodology

Although occupational epidemiological studies and animal experimentation provide strong evidence that radon-222 (222Rn) progeny exposure causes lung cancer, residential epidemiological studies have not confirmed this association. Past residential epidemiological studies have yielded contradictory findings. Exposure misclassification has seriously compromised the ability of these studies to detect whether an association exists between 222Rn exposure and lung cancer. Misclassification of 222Rn exposure has arisen primarily from: 1) detector measurement error; 2) failure to consider temporal and spatial 222Rn variations within a home; 3) missing data from previously occupied homes that currently are inaccessible; 4) failure to link 222Rn concentrations with subject mobility; and 5) measuring 222Rn gas concentration as a surrogate for 222Rn progeny exposure. This paper examines these methodological dosimetry problems and addresses how we are accounting for them in an ongoing, population-based, case-control study of 222Rn and lung cancer in Iowa

Evaluation of azlocillin in-vitro and in discriminative animal models of infection

Azlocillin was more active in vitro than ticarcillin or carbenicillin against 561 aminoglycoside-resistant strains of Pseudomonas aeruginosa collected from 74 hospitals distributed over a wide geographic area in the eastern United States. Azlocillin was compared with various other antimicrobial agents in discriminative animal models of Ps. aeruginosa pyelonephritis, osteomyelitis, endocarditis, and meningitis in a variety of mammalian species. Cefsulodin was more effective than azlocillin in reducing Ps. aeruginosa kidney concentrations in rat pyelonephritis induced by intrarenal inoculation. The mean±s.d. logl0 cfu/g kidney after three days of therapy were as follows: controls = 5.4±1.5, azlocillin = 4.4±1.8, cefsulodin = 2.6±0.9 (P < 0.01) but the MBC for the test strain was eight-fold higher for azlocillin (8 vs. 1 mg/l) and effective concentrations were maintained longer in rat serum for cefsulodin as against azlocillin. In addition, ticarcillin reduced kidney bacterial concentrations faster than azlocillin in a mouse pyelonephritis model induced by intravenous Ps. aeruginosa inoculation with subsequent iron loading. Azlocillin was less effective than tobramycin in experimental chronic Ps. aeruginosa osteomyelitis induced in rabbits by direct injection into the tibia. An azlocillin-tobramycin regimen was not more effective than tobramycin alone. After 28 days of therapy, the percentages of positive bone cultures after death were as follows: no antibiotic (controls) = 92%, azlocillin = 95%, tobramycin = 76%, azlocillin plus tobramycin = 60%. Both ticarcillin and azlocillin were less active than tobramycin in experimental Ps. aeruginosa endocarditis induced in rabbits by intravenous inoculation of 108 cfu following 1 h of catheter induced aortic valve trauma. The best results were noted with an azlocillin-tobramycin regimen. The mean±s.d. log10 cfu Ps. aeruginosa/g vegetation after five days of therapy were as follows: no antibiotic controls = 8.1 ± 1.1, tobramycin = 4.5 ±0.8, ticarcillin = 6.9 ± 0.8, azlocillin = 5.7 ± 1.5, ticarcillin phis tobramycin = 4.9 ± 1.0, azlocillin plus tobramycin = 3.3 ± 1.6. Sterile vegetations were rarely attained with any regimen. The mean percentage penetration into purulent cerebrospinal fluid (CSF) in experimental Ps. aeruginosa meningitis for azlocillin was 13.3%, comparable to many other β-lactam antibiotics. Azlocillin was the single most active (P < 0.01) agent evaluated after 8 h intravenous infusions in this model. An azlocillin-amikacin regimen was more rapidly bactericidal (P < 0.01) than either agent alone in vivo. None of the agents evaluated alone or in combination, however, produced a sterile CSF after 8 h of therapy in any anima

Numerical relativity surrogate model with memory effects and post-Newtonian hybridization

Numerical relativity simulations provide the most precise templates for the gravitational waves produced by binary black hole mergers. However, many of these simulations use an incomplete waveform extraction technique -- extrapolation -- that fails to capture important physics, such as gravitational memory effects. Cauchy-characteristic evolution (CCE), by contrast, is a much more physically accurate extraction procedure that fully evolves Einstein's equations to future null infinity and accurately captures the expected physics. In this work, we present a new surrogate model, NRHybSur3dq8$\_$CCE, built from CCE waveforms that have been mapped to the post-Newtonian (PN) BMS frame and then hybridized with PN and effective one-body (EOB) waveforms. This model is trained on 102 waveforms with mass ratios $q\leq8$ and aligned spins $\chi_{1z}, \, \chi_{2z} \in \left[-0.8, 0.8\right]$. The model spans the entire LIGO-Virgo-KAGRA (LVK) frequency band (with $f_{\text{low}}=20\text{Hz}$) for total masses $M\gtrsim2.25M_{\odot}$ and includes the $\ell\leq4$ and $(\ell,m)=(5,5)$ spin-weight $-2$ spherical harmonic modes, but not the $(3,1)$, $(4,2)$ or $(4,1)$ modes. We find that NRHybSur3dq8$\_$CCE can accurately reproduce the training waveforms with mismatches $\lesssim2\times10^{-4}$ for total masses $2.25M_{\odot}\leq M\leq300M_{\odot}$ and can, for a modest degree of extrapolation, capably model outside of its training region. Most importantly, unlike previous waveform models, the new surrogate model successfully captures memory effects.Comment: 14 pages, 11 figures. Accepted for publication in PR

Evolution and networks in ancient and widespread symbioses between Mucoromycotina and liverworts

Like the majority of land plants, liverworts regularly form intimate symbioses with arbuscular mycorrhizal fungi (Glomeromycotina). Recent phylogenetic and physiological studies report that they also form intimate symbioses with Mucoromycotina fungi and that some of these, like those involving Glomeromycotina, represent nutritional mutualisms. To compare these symbioses, we carried out a global analysis of Mucoromycotina fungi in liverworts and other plants using species delimitation, ancestral reconstruction, and network analyses. We found that Mucoromycotina are more common and diverse symbionts of liverworts than previously thought, globally distributed, ancestral, and often co-occur with Glomeromycotina within plants. However, our results also suggest that the associations formed by Mucoromycotina fungi are fundamentally different because, unlike Glomeromycotina, they may have evolved multiple times and their symbiotic networks are un-nested (i.e., not forming nested subsets of species). We infer that the global Mucoromycotina symbiosis is evolutionarily and ecologically distinctive

Canfam GSD: De novo chromosome-length genome assembly of the German Shepherd Dog (Canis lupus familiaris) using a combination of long reads, optical mapping, and Hi-C

Background: The German Shepherd Dog (GSD) is one of the most common breeds on earth and has been bred for its utility and intelligence. It is often first choice for police and military work, as well as protection, disability assistance, and search-and-rescue. Yet, GSDs are well known to be susceptible to a range of genetic diseases that can interfere with their training. Such diseases are of particular concern when they occur later in life, and fully trained animals are not able to continue their duties. Findings: Here, we provide the draft genome sequence of a healthy German Shepherd female as a reference for future disease and evolutionary studies. We generated this improved canid reference genome (CanFam GSD) utilizing a combination of Pacific Bioscience, Oxford Nanopore, 10X Genomics, Bionano, and Hi-C technologies. The GSD assembly is ∼80 times as contiguous as the current canid reference genome (20.9 vs 0.267 Mb contig N50), containing far fewer gaps (306 vs 23,876) and fewer scaffolds (429 vs 3,310) than the current canid reference genome CanFamv3.1. Two chromosomes (4 and 35) are assembled into single scaffolds with no gaps. BUSCO analyses of the genome assembly results show that 93.0% of the conserved single-copy genes are complete in the GSD assembly compared with 92.2% for CanFam v3.1. Homology-based gene annotation increases this value to ∼99%. Detailed examination of the evolutionarily important pancreatic amylase region reveals that there are most likely 7 copies of the gene, indicative of a duplication of 4 ancestral copies and the disruption of 1 copy. Conclusions: GSD genome assembly and annotation were produced with major improvement in completeness, continuity, and quality over the existing canid reference. This resource will enable further research related to canine diseases, the evolutionary relationships of canids, and other aspects of canid biology

Challenges in quantifying changes in the global water cycle

Human influences have likely already impacted the large-scale water cycle but natural variability and observational uncertainty are substantial. It is essential to maintain and improve observational capabilities to better characterize changes. Understanding observed changes to the global water cycle is key to predicting future climate changes and their impacts. While many datasets document crucial variables such as precipitation, ocean salinity, runoff, and humidity, most are uncertain for determining long-term changes. In situ networks provide long time-series over land but are sparse in many regions, particularly the tropics. Satellite and reanalysis datasets provide global coverage, but their long-term stability is lacking. However, comparisons of changes among related variables can give insights into the robustness of observed changes. For example, ocean salinity, interpreted with an understanding of ocean processes, can help cross-validate precipitation. Observational evidence for human influences on the water cycle is emerging, but uncertainties resulting from internal variability and observational errors are too large to determine whether the observed and simulated changes are consistent. Improvements to the in situ and satellite observing networks that monitor the changing water cycle are required, yet continued data coverage is threatened by funding reductions. Uncertainty both in the role of anthropogenic aerosols, and due to large climate variability presently limits confidence in attribution of observed changes

Social capital: a roadmap of theoretical and empirical contributions and limitations

The general idea of social capital is that relationships matter. In this sense, the trust, cooperation and reciprocity involved in these relationships can have a positive impact on the wealth of society by reducing transaction costs, facilitating collective actions, and lowering opportunistic behavior. This work sheds light on the different theoretical and empirical problems that a scholar is likely to face in dealing with social capital research and analysis. We propose a critical roadmap of the social capital theories and applications for a general audience, nonusers included, with particular attention to the works of political and social economists. We provide a critical debate on the different definitions and measures produced, the theoretical frameworks developed, and the empirical techniques adopted so far in the analysis of the impact of social capital on socio-economic outcomes. We turn to the limitations of these techniques and suggest some basic strategies to reduce the magnitude of these limitations

The Australian dingo is an early offshoot of modern breed dogs

Dogs are uniquely associated with human dispersal and bring transformational insight into the domestication process. Dingoes represent an intriguing case within canine evolution being geographically isolated for thousands of years. Here, we present a high-quality de novo assembly of a pure dingo (CanFam_DDS). We identified large chromosomal differences relative to the current dog reference (CanFam3.1) and confirmed no expanded pancreatic amylase gene as found in breed dogs. Phylogenetic analyses using variant pairwise matrices show that the dingo is distinct from five breed dogs with 100% bootstrap support when using Greenland wolf as the outgroup. Functionally, we observe differences in methylation patterns between the dingo and German shepherd dog genomes and differences in serum biochemistry and microbiome makeup. Our results suggest that distinct demographic and environmental conditions have shaped the dingo genome. In contrast, artificial human selection has likely shaped the genomes of domestic breed dogs after divergence from the dingo

Metabolic and morphological alterations induced by proteolysis-inducing factor from Walker tumour-bearing rats in C2C12 myotubes

BACKGROUND: Patients with advanced cancer suffer from cachexia, which is characterised by a marked weight loss, and is invariably associated with the presence of tumoral and humoral factors which are mainly responsible for the depletion of fat stores and muscular tissue. METHODS: In this work, we used cytotoxicity and enzymatic assays and morphological analysis to examine the effects of a proteolysis-inducing factor (PIF)-like molecule purified from ascitic fluid of Walker tumour-bearing rats (WF), which has been suggested to be responsible for muscle atrophy, on cultured C2C12 muscle cells. RESULTS: WF decreased the viability of C2C12 myotubes, especially at concentrations of 20-25 mug.mL-1. There was an increase in the content of the pro-oxidant malondialdehyde, and a decrease in antioxidant enzyme activity. Myotubes protein synthesis decreased and protein degradation increased together with an enhanced in the chymotrypsin-like enzyme activity, a measure of functional proteasome activity, after treatment with WF. Morphological alterations such as cell retraction and the presence of numerous cells in suspension were observed, particularly at high WF concentrations. CONCLUSION: These results indicate that WF has similar effects to those of proteolysis-inducing factor, but is less potent than the latter. Further studies are required to determine the precise role of WF in this experimental model. © 2008 Yano et al; licensee BioMed Central Ltd