Lung diseases remain a significant and devastating cause of morbidity and mortality worldwide. In contrast to many other major diseases, lung diseases notably chronic obstructive pulmonary diseases ...(COPDs), including both asthma and emphysema, are increasing in prevalence and COPD is expected to become the third leading cause of disease mortality worldwide by 2020. New therapeutic options are desperately needed. A rapidly growing number of investigations of stem cells and cell therapies in lung biology and diseases as well as in ex vivo lung bioengineering have offered exciting new avenues for advancing knowledge of lung biology as well as providing novel potential therapeutic approaches for lung diseases. These initial observations have led to a growing exploration of endothelial progenitor cells and mesenchymal stem (stromal) cells in clinical trials of pulmonary hypertension and COPD with other clinical investigations planned. Ex vivo bioengineering of the trachea, larynx, diaphragm, and the lung itself with both biosynthetic constructs as well as decellularized tissues have been used to explore engineering both airway and vascular systems of the lung. Lung is thus a ripe organ for a variety of cell therapy and regenerative medicine approaches. Current state‐of‐the‐art progress for each of the above areas will be presented as will discussion of current considerations for cell therapy‐based clinical trials in lung diseases. Stem Cells 2014;32:16–25
Genome editing has therapeutic potential for treating genetic diseases and cancer. However, the currently most practicable approaches rely on the generation of DNA double-strand breaks (DSBs), which ...can give rise to a poorly characterized spectrum of chromosome structural abnormalities. Here, using model cells and single-cell whole-genome sequencing, as well as by editing at a clinically relevant locus in clinically relevant cells, we show that CRISPR-Cas9 editing generates structural defects of the nucleus, micronuclei and chromosome bridges, which initiate a mutational process called chromothripsis. Chromothripsis is extensive chromosome rearrangement restricted to one or a few chromosomes that can cause human congenital disease and cancer. These results demonstrate that chromothripsis is a previously unappreciated on-target consequence of CRISPR-Cas9-generated DSBs. As genome editing is implemented in the clinic, the potential for extensive chromosomal rearrangements should be considered and monitored.
The localization of a stationary transmitter using receivers mounted on fast moving platforms is considered. It is assumed that the transmitted radio signal is random with known statistics. The ...conventional approach is based on two steps. In the first step the time difference of arrival and the differential Doppler shift are measured and in the second step these measurements are used for geolocation. We advocate a direct position determination approach that proves to be more computationally efficient and more precise for weak signals than the conventional approach. The direct method is a single-step method that uses the same signals as the two-step approach but searches directly for the emitter position without first estimating intermediate parameters such as Doppler frequency and the time delay. A secondary but important result is a derivation of closed-form and compact expressions of the Cramér-Rao lower bound. All results are verified by Monte Carlo computer simulations.
There is a significant gap in understanding the risk of sexual victimization in individuals with autism spectrum disorders (ASD) and the variables that contribute to risk. Age appropriate sexual ...interest, limited sexual knowledge and experiences, and social deficits, may place adults with ASD at increased risk. Ninety-five adults with ASD and 117 adults without ASD completed questionnaires regarding sexual knowledge sources, actual knowledge, perceived knowledge, and sexual victimization. Individuals with ASD obtained less of their sexual knowledge from social sources, more sexual knowledge from non-social sources, had less perceived and actual knowledge, and experienced more sexual victimization than controls. The increased risk of victimization by individuals with ASD was partially mediated by their actual knowledge. The link between knowledge and victimization has important clinical implications for interventions.
Using buoy data from the International Arctic Buoy Program, we found that the sea ice mean speed has substantially increased over the last 29 years (+17% per decade for winter and +8.5% for summer). ...A strong seasonal dependence of the mean speed is also revealed, with a maximum in October and a minimum in April. The sea ice mean strain rate also increased significantly over the period (+51% per decade for winter and +52% for summer). We check that these increases in both sea ice mean speed and deformation rate are unlikely to be consequences of a stronger atmospheric forcing. Instead, they suggest that sea ice kinematics play a fundamental role in the albedo feedback loop and sea ice decline: increasing deformation means stronger fracturing, hence more lead opening, and therefore a decreasing albedo. This accelerates sea ice thinning in summer and delays refreezing in early winter, therefore decreasing the mechanical strength of the cover and allowing even more fracturing, larger drifting speed and deformation, and possibly a faster export of sea ice through the Fram Strait. The September minimum sea ice extent of 2007 might be a good illustration of this interplay between sea ice deformation and sea ice shrinking, as we found that for both winter 2007 and summer 2007 exceptionally large deformation rates affected the Arctic sea ice cover.
The economic and man-made resources that sustain human wellbeing are not distributed evenly across the world, but are instead heavily concentrated in cities. Poor access to opportunities and services ...offered by urban centres (a function of distance, transport infrastructure, and the spatial distribution of cities) is a major barrier to improved livelihoods and overall development. Advancing accessibility worldwide underpins the equity agenda of 'leaving no one behind' established by the Sustainable Development Goals of the United Nations. This has renewed international efforts to accurately measure accessibility and generate a metric that can inform the design and implementation of development policies. The only previous attempt to reliably map accessibility worldwide, which was published nearly a decade ago, predated the baseline for the Sustainable Development Goals and excluded the recent expansion in infrastructure networks, particularly in lower-resource settings. In parallel, new data sources provided by Open Street Map and Google now capture transportation networks with unprecedented detail and precision. Here we develop and validate a map that quantifies travel time to cities for 2015 at a spatial resolution of approximately one by one kilometre by integrating ten global-scale surfaces that characterize factors affecting human movement rates and 13,840 high-density urban centres within an established geospatial-modelling framework. Our results highlight disparities in accessibility relative to wealth as 50.9% of individuals living in low-income settings (concentrated in sub-Saharan Africa) reside within an hour of a city compared to 90.7% of individuals in high-income settings. By further triangulating this map against socioeconomic datasets, we demonstrate how access to urban centres stratifies the economic, educational, and health status of humanity.
Pet cats may be used as a biomarker for assessing exposures to organohalogen compounds (OHCs) adsorbed to household dust in home environments. This study explores two exposure routes of OHCs, ...ingestion of OHCs (i) via house dust and (ii) via cat food. House dust from 17 Swedish homes and serum from the participating families’ pet cats were collected, and cat food was purchased matching the diet reported. Paired samples of cat serum, house dust, and cat food were analyzed for brominated flame retardants/natural products (polybrominated diphenyl ethers (PBDEs), decabromobiphenyl (BB-209), decabromodiphenyl ethane (DBDPE), 2,4,6-tribromophenol (2,4,6-TBP), OH-PBDEs) and organochlorines (polychlorinated biphenyls (PCBs), 1,1-bis(4,4′-dichlorodiphenyl)-2,2,2-trichloroethane (4,4′-DDT), 1,1-bis(4,4′-dichlorodiphenyl)-2,2-dichloroethene (4,4′-DDE), hexachlorobenzene (HCB), pentachlorophenol (PCP)). Significant correlations were found between serum and dust samples from the living rooms for BDE-47 (p < 0.035), BDE-99 (p < 0.035), and BDE-153 (p < 0.039), from the adult’s bedroom for BDE-99 (p < 0.019) and from all rooms for BDE-99 (p < 0.020) and BB-209 (p < 0.048). This is the first time a correlation between cat serum levels and household dust has been established, a finding that supports the hypothesis that dust is a significant exposure route for cats. Serum levels were also significantly correlated with concentrations found in cat food for 6-OH-BDE47 (p < 0.002), 2,4,6-TBP (p < 0.035), and BB-209 (p < 0.007). DBDPE was found in high concentrations in all dust (median 154 pmol/g) and food samples (median 0.7 pmol/g lw) but was below detection in serum samples, suggesting low or no bioavailability for DBDPE in cats.
This book examines a remarkable political phenomenon--the dramatic shift of black voters from the Republican to the Democratic party in the 1930s, a shift all the more striking in light of the ...Democrats' indifference to racial concerns. Nancy J. Weiss shows that blacks became Democrats in response to the economic benefits of the New Deal and that they voted for Franklin Roosevelt in spite of the New Deal's lack of a substantive record on race. By their support for FDR blacks forged a political commitment to the Democratic party that has lasted to our own time. The last group to join the New Deal coalition, they have been the group that remained the most loyal to the Democratic party. This book explains the sources of their commitment in the 1930s. It stresses the central role of economic concerns in shaping black political behavior and clarifies both the New Deal record on race and the extraordinary relationship between black voters and the Roosevelts.
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