Application of compact laser-driven accelerator X-ray sources for industrial imaging

X-rays generated by betatron oscillations of electrons in a laser-driven plasma accelerator were characterised and applied to imaging industrial samples. With a 125TW laser, a low divergence beam with 5.2±1.7 × 107photonsmrad−2 per pulse was produced with a synchrotron spectrum with a critical energy of 14.6±1.3keV. Radiographs were obtained of a metrology test sample, battery electrodes, and a damage site in a composite material. These results demonstrate the suitability of the source for non-destructive evaluation applications. The potential for industrial implementation of plasma accelerators is discussed

Increased Mortality in SDHB but Not in SDHD Pathogenic Variant Carriers

Germline mutations in succinate dehydrogenase subunit B and D (SDHB and SDHD) are predisposed to hereditary paraganglioma (PGL) and pheochromocytoma (PHEO). The phenotype of pathogenic variants varies according to the causative gene. In this retrospective study, we estimate the mortality of a nationwide cohort of SDHB variant carriers and that of a large cohort of SDHD variant carriers and compare it to the mortality of a matched cohort of the general Dutch population. A total of 192 SDHB variant carriers and 232 SDHD variant carriers were included in this study. The Standard Mortality Ratio (SMR) for SDHB mutation carriers was 1.89, increasing to 2.88 in carriers affected by PGL. For SDHD variant carriers the SMR was 0.93 and 1.06 in affected carriers. Compared to the general population, mortality seems to be increased in SDHB variant carriers, especially in those affected by PGL. In SDHD variant carriers, the mortality is comparable to that of the general Dutch population, even if they are affected by PGL. This insight emphasizes the significance of DNA-testing in all PGL and PHEO patients, since different clinical risks may warrant gene-specific management strategies

Phenotyping of Nod1/2 double deficient mice and characterization of Nod1/2 in systemic inflammation and associated renal disease

Contains fulltext : 109047.pdf (publisher's version ) (Open Access)It is indispensable to thoroughly characterize each animal model in order to distinguish between primary and secondary effects of genetic changes. The present study analyzed Nod1 and Nod2 double deficient (Nod1/2 DKO) mice under physiological and inflammatory conditions. Nod1 and Nod2 are members of the Nucleotide-binding domain and Leucine-rich repeat containing Receptor (NLR) family. Several inflammatory disorders, such as Crohn's disease and asthma, are linked to genetic changes in either Nod1 or Nod2. These associations suggest that Nod1 and Nod2 play important roles in regulating the immune system.Three-month-old wildtype (Wt) and Nod1/2 DKO mice were sacrificed, body and organ weight were determined, and blood was drawn. Except for lower liver weight in Nod1/2 DKO mice, no differences were found in body/organ weight between both strains. Leukocyte count and composition was comparable. No significant changes in analyzed plasma biochemical markers were found. Additionally, intestinal and vascular permeability was determined. Nod1/2 DKO mice show increased susceptibility for intestinal permeability while vascular permeability was not affected. Next we induced septic shock and organ damage by administering LPS+PGN intraperitoneally to Wt and Nod1/2 DKO mice and sacrificed animals after 2 and 24 hours. The systemic inflammatory and metabolic response was comparable between both strains. However, renal response was different as indicated by partly preserved kidney function and tubular epithelial cell damage in Nod1/2 DKO at 24 hours. Remarkably, renal inflammatory mediators Tnfalpha, KC and Il-10 were significantly increased in Nod1/2 DKO compared with Wt mice at 2 hours.Systematic analysis of Nod1/2 DKO mice revealed a possible role of Nod1/2 in the development of renal disease during systemic inflammation

Controversies on the management of the clinically negative neck

Adequate management of the clinically negative neck is vital and should be balanced between over and undertreatment. Compared to clinical examination ultrasound-guided fine-needle aspiration cytology (USgFNAC) at initial staging can reduce the risk of occult metastases for T1-T2 squamous cell carcinoma of the oral cavity or oropharynx considerably to 20%, which justifies local excision of the tumour and a wait-and-see policy for the neck. SN identification and aspiration did not decrease the false-negative rate, and we have therefore abandoned its use in this setting. Using USgFNAC for follow-up enabled early detection of a significant percentage of neck failures and a high salvage rate with therapeutic neck dissection of 80%. Detecting subclinical neck metastases continues to challenge clinicians and debate continues

TREM-1 and its potential ligands in non-infectious diseases: from biology to clinical perspectives

Contains fulltext : 177974.pdf (Publisher’s version ) (Open Access)Triggering receptor expressed on myeloid cells-1 (TREM-1) is expressed on the majority of innate immune cells and to a lesser extent on parenchymal cells. Upon activation, TREM-1 can directly amplify an inflammatory response. Although it was initially demonstrated that TREM-1 was predominantly associated with infectious diseases, recent evidences shed new light into its role in sterile inflammatory diseases. Indeed, TREM-1 receptor and its signaling pathways contribute to the pathology of several non-infectious acute and chronic inflammatory diseases, including atherosclerosis, ischemia reperfusion-induced tissue injury, colitis, fibrosis and cancer. This review, aims to give an extensive overview of TREM-1 in non-infectious diseases, with the focus on the therapeutic potential of TREM-1 intervention strategies herein. In addition, we provide the reader with a functional enrichment analysis of TREM-1 signaling pathway and potential TREM-1 ligands in these diseases, obtained via in silico approach. We discuss pre-clinical studies which show that TREM-1 inhibition, via synthetic soluble TREM-1 protein mimickers, is effective in treating (preventing) specific inflammatory disorders, without significant effects on antibacterial response. Further research aimed at identifying specific TREM-1 ligands, in different inflammatory disorders, is required to further unravel the role of this receptor, and explore new avenues to modulate its function