Single-shot, charge-dependent emittance measurements of electron beams generated by a laser plasma accelerator (LPA) reveal that shock-induced density down-ramp injection produces beams with ...normalized emittances a factor of 2 smaller than beams produced via ionization injection. Such a comparison is made possible by the tunable LPA setup, which allows electron beams with nearly identical central energy and peak spectral charge density to be produced using the two distinct injection mechanisms. Parametric measurements of this type are essential for the development of LPA-based applications which ultimately require high charge density and low emittance.
Laser-plasma accelerators of only a centimetre's length have produced nearly monoenergetic electron bunches with energy as high as 1 GeV. Scaling these compact accelerators to multi-gigaelectronvolt ...energy would open the prospect of building X-ray free-electron lasers and linear colliders hundreds of times smaller than conventional facilities, but the 1 GeV barrier has so far proven insurmountable. Here, by applying new petawatt laser technology, we produce electron bunches with a spectrum prominently peaked at 2 GeV with only a few per cent energy spread and unprecedented sub-milliradian divergence. Petawatt pulses inject ambient plasma electrons into the laser-driven accelerator at much lower density than was previously possible, thereby overcoming the principal physical barriers to multi-gigaelectronvolt acceleration: dephasing between laser-driven wake and accelerating electrons and laser pulse erosion. Simulations indicate that with improvements in the laser-pulse focus quality, acceleration to nearly 10 GeV should be possible with the available pulse energy.
To cite this article: Liu X, Wang G, Hong X, Wang D, Tsai H‐J, Zhang S, Arguelles L, Kumar R, Wang H, Liu R, Zhou Y, Pearson C, Ortiz K, Schleimer R, Holt P, Pongracic J, Price HE, Langman C, Wang X. ...Gene–vitamin D interactions on food sensitization: a prospective birth cohort study. Allergy 2011; 66: 1442–1448.
Background: It has been hypothesized that vitamin D deficiency (VDD) contributes to the development of food sensitization (FS) and then food allergy. However, the epidemiological evidence is conflicting. We aim to examine whether cord blood VDD is associated with FS and whether such association can be modified by genetic variants in a prospective birth cohort.
Methods: This study included 649 children who were enrolled at birth and followed from birth onward at the Boston Medical Center. We defined VDD as cord blood 25(OH)D < 11 ng/ml, and FS as specific IgE ≥ 0.35 kUA/l to any of eight common food allergens in early childhood. We genotyped potentially functional single‐nucleotide polymorphisms (SNPs) in 11 genes known to be involved in regulating IgE and 25(OH)D concentrations. Logistic regressions were used to test the effects of VDD on FS individually and jointly with SNPs.
Results: Among the 649 children, 44% had VDD and 37% had FS. When examined alone, VDD was not associated with FS. When examined jointly with SNPs, a significant interaction between IL4 gene polymorphism (rs2243250) and VDD (pinteraction = 0.003, pFDR = 0.10) was found: VDD increased the risk of FS among children carrying CC/CT genotypes (OR = 1.79, 95%CI: 1.15–2.77). Similar but weaker interactions were observed for SNPs in MS4A2 (rs512555), FCER1G (rs2070901), and CYP24A1 (rs2762934). When all four SNPs were simultaneously considered, a strong gene–VDD interaction was evident (pinteraction = 9 × 10−6).
Conclusions: Our data demonstrate that VDD may increase the risk of FS among individuals with certain genotypes, providing evidence of gene–vitamin D interaction on FS.
High-throughput three-dimensional cryogenic imaging of thick biological specimens is valuable for identifying biologically- or pathologically-relevant features of interest, especially for subsequent ...correlative studies. Unfortunately, high-resolution imaging techniques at cryogenic conditions often require sample reduction through sequential physical milling or sectioning for sufficient penetration to generate each image of the 3-D stack. This study represents the first demonstration of using ptychographic hard X-ray tomography at cryogenic temperatures for imaging thick biological tissue in a chemically-fixed, frozen-hydrated state without heavy metal staining and organic solvents. Applied to mammalian brain, this label-free cryogenic imaging method allows visualization of myelinated axons and sub-cellular features such as age-related pigmented cellular inclusions at a spatial resolution of ~100 nanometers and thicknesses approaching 100 microns. Because our approach does not require dehydration, staining or reduction of the sample, we introduce the possibility for subsequent analysis of the same tissue using orthogonal approaches that are expected to yield direct complementary insight to the biological features of interest.
Summary
Proximal humeral fracture is the third most common osteoporotic fracture. To our knowledge, this is the first nationwide population-based registry study in adults that includes both inpatient ...and outpatient visits. Thus, we were able to report the true incidence rates and trends in the treatment of proximal humeral fractures.
Introduction
Proximal humeral fractures are among the most common osteoporotic fractures. Valid epidemiologic population-based data, including both inpatient and outpatient visits, however, are lacking.
Methods
To investigate the Swedish national incidence rates and treatment trends of proximal humeral fractures, we obtained data from the Swedish Hospital Discharge Register between 2001 and 2012. All adult patients (≥18 years of age) in the Swedish Hospital Discharge Register were included. Outpatient visits have been included in the register since 2001.
Results
We identified 98,770 patients (women
n
= 72,063; 73 %) with proximal humeral fractures between 2001 and 2012. In 2001, the sex-specific incidence of proximal humeral fractures was 134.5 per 100,000 person-years for women and 49.2 for men. In 2012, the corresponding values were 174.6 for women and 68.1 for men, increasing 30 % in women and 39 % in men. A total of 17,013 surgical procedures were conducted between 2001 and 2012. Open reduction and internal fixation with a plate was the most common procedure (
n
= 5050, 30 %), followed by endoprosthetic implantation (
n
= 3962, 23 %) and intramedullary nailing (
n
= 3376, 20 %). The proportion of surgically treated patients increased from 12.1 % in 2001 to 16.8 % in 2012 for women and from 15.1 % in 2001 to 17.1 % in 2012 for men.
Conclusion
The Swedish national incidence of proximal humeral fractures has been increasing, although it seems to have peaked in the elderly population during 2008–2010. The rate of surgical treatment has increased substantially, particularly open reduction and internal fixation with a plate. To our knowledge, this is the first nationwide epidemiologic study for Sweden reporting the incidence of proximal humeral fractures and including all inpatient and outpatient visits.
The 3-30-300 rule offers benchmarks for cities to promote equitable nature access. It dictates that individuals should see three trees from their dwelling, have 30 % tree canopy in their ...neighborhood, and live within 300 m of a high-quality green space. Implementing this demands thorough measurement, monitoring, and evaluation methods, yet little guidance is currently available to pursue these actions. To overcome this gap, we employed an expert-based consensus approach to review the available ways to measure 3-30-300 as well as each measure's strengths and weaknesses. We described seven relevant data and processes: vegetation indices, street level analyses, tree inventories, questionnaires, window view analyses, land cover maps, and green space maps. Based on the reviewed strengths and weaknesses of each measure, we presented a suitability matrix to link recommended measures with each component of the rule. These recommendations included surveys and window-view analyses for the '3 component', high-resolution land cover maps for the '30 component', and green space maps with network analyses for the '300 component'. These methods, responsive to local situations and resources, not only implement the 3-30-300 rule but foster broader dialogue on local desires and requirements. Consequently, these techniques can guide strategic investments in urban greening for health, equity, biodiversity, and climate adaptation.
Background and purpose:
Inhibition of cholesteryl ester transfer protein (CETP) with torcetrapib in humans increases plasma high density lipoprotein (HDL) cholesterol levels but is associated with ...increased blood pressure. In a phase 3 clinical study, evaluating the effects of torcetrapib in atherosclerosis, there was an excess of deaths and adverse cardiovascular events in patients taking torcetrapib. The studies reported herein sought to evaluate off‐target effects of torcetrapib.
Experimental approach:
Cardiovascular effects of the CETP inhibitors torcetrapib and anacetrapib were evaluated in animal models.
Key results:
Torcetrapib evoked an acute increase in blood pressure in all species evaluated whereas no increase was observed with anacetrapib. The pressor effect of torcetrapib was not diminished in the presence of adrenoceptor, angiotensin II or endothelin receptor antagonists. Torcetrapib did not have a contractile effect on vascular smooth muscle suggesting its effects in vivo are via the release of a secondary mediator. Treatment with torcetrapib was associated with an increase in plasma levels of aldosterone and corticosterone and, in vitro, was shown to release aldosterone from adrenocortical cells. Increased adrenal steroid levels were not observed with anacetrapib. Inhibition of adrenal steroid synthesis did not inhibit the pressor response to torcetrapib whereas adrenalectomy prevented the ability of torcetrapib to increase blood pressure in rats.
Conclusions and implications:
Torcetrapib evoked an acute increase in blood pressure and an acute increase in plasma adrenal steroids. The acute pressor response to torcetrapib was not mediated by adrenal steroids but was dependent on intact adrenal glands.
British Journal of Pharmacology (2008) 154, 1465–1473; doi:fn2; published online 9 June 2008
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