Static and dynamic failure load of fiber-reinforced composite and particulate filler composite cantilever resin-bonded fixed dental prostheses

Purpose: The aim of this study was to evaluate in vitro the influence of fiber reinforcement and luting cement on the static failure load (SFL) and dynamic failure load (DFL) of simulated two-unit cantilever resin-bonded fixed dental prostheses (RBFDPs). Materials and Methods: Forty-six particulate filler composite (PFC) beams and 76 fiber-reinforced composite (FRC) beams were prefabricated and subsequently luted (RelyX ARC or Panavia F2.0) onto flat ground bovine enamel. The SFL of the different specimen types was determined with a peel test and the DEL was determined with a rotating cantilever beam fatigue testing device. Results: The PFC specimens showed a significantly lower SFL than the FRC specimens. The luting cement showed a significant effect on the SFL of the PFC specimens, but not with FRC. The DEL of PFC specimens was significantly lower than for FRC specimens. The luting cement showed a significant effect on the DFL of the PFC specimens, but not so with FRC. With both the SFL and the DEL tests all PFC beams fractured, leaving the bonded part on the tooth surface, but FRC beams partially debonded from the tooth surface, leaving fibers connected to the enamel surface to a varying extent. Coincidentally, the uncured fibers turned out to be prone to aging, an effect which has been investigated. Conclusion: Within the limitations of this study, it can be concluded that PFC without fiber reinforcement is not suitable for the fabrication of two-unit cantilever RBFDPs, despite the significant effect of the luting cement, but FRC is suitable

Standardization for Defence Procurement - European Handbook : CEN Workshop 10

The European Commission (EC), DG Enterprise, endeavours the competitiveness of the European Defence Industry. The plethora of (national) standards, more than 10.000, are recognised by the EC as a major constraint and cost driver. Electromagnetic Compatibility (EMC) or Electromagnetic Environmental Effects (EEE) are considered by the EC as a major topic, with 7 other topics such as environmental engineering, energetic materials, batteries, electrical interfaces. An EMC expert group with representatives from industry, including Aerotech Telub, Intellect, EADS, Ericsson Microwave, Fincantieri, MBDA, Thales, and national MoDs rationalized in 2004 a list of 329 EEE standards, implicitly abandoning national, including American, standards, and develop guidelines for the procurement process. A limited number of widely accepted and cost effective standards, suitable for use by MoD’s (acquisition) and industry (product development), has been defined after making comparisons. Comparisons were carried out on some standards against STANAG 4370 AECTP 500. The Expert Group agreed; That no one standard is better or worse than another in achieving an end goal. Differences are not sufficient to prevent the use of AECTP 500. There are sufficient similarities to AECTP 500 to adopt this as the fundamental replacement standard. There was sufficient agreement on NATO-, IEC- and EN-produced standards to make worthwhile agreement to use a number of standards as replacement for some (or some parts) of existing National Standards. This document gives recommendations on the use of the standards, the scope and \ud limitations. It also emphasizes the constraints with respect to the standardisation process of National MoD’s, NATO, Industry and EN/IEC

Ivermectin treatment of Loa loa hyper-microfilaraemic baboons (Papio anubis): Assessment of microfilarial loads, haematological and biochemical parameters and histopathological changes following treatment.

Individuals with high intensity of Loa loa are at risk of developing serious adverse events (SAEs) post treatment with ivermectin. These SAEs have remained unclear and a programmatic impediment to the advancement of community directed treatment with ivermectin. The pathogenesis of these SAEs following ivermectin has never been investigated experimentally. The Loa/baboon (Papio anubis) model can be used to investigate the pathogenesis of Loa-associated encephalopathy following ivermectin treatment in humans. 12 baboons with microfilarial loads > 8,000mf/mL of blood were randomised into four groups: Group 1 (control group receiving no drug), Group 2 receiving ivermectin (IVM) alone, Group 3 receiving ivermectin plus aspirin (IVM + ASA), and Group 4 receiving ivermectin plus prednisone (IVM + PSE). Blood samples collected before treatment and at Day 5, 7 or 10 post treatment, were analysed for parasitological, hematological and biochemical parameters using standard techniques. Clinical monitoring of animals for side effects took place every 6 hours post treatment until autopsy. At autopsy free fluids and a large number of standard organs were collected, examined and tissues fixed in 10% buffered formalin and processed for standard haematoxylin-eosin staining and specific immunocytochemical staining. Mf counts dropped significantly (p0.05). All animals became withdrawn 48 hours after IVM administration. All treated animals recorded clinical manifestations including rashes, itching, diarrhoea, conjunctival haemorrhages, lymph node enlargement, pinkish ears, swollen face and restlessness; one animal died 5 hours after IVM administration. Macroscopic changes in post-mortem tissues observed comprised haemorrhages in the brain, lungs, heart, which seen in all groups given ivermectin but not in the untreated animals. Microscopically, the major cellular changes seen, which were present in all the ivermectin treated animals included microfilariae in varying degrees of degeneration in small vessels. These were frequently associated with fibrin deposition, endothelial changes including damage to the integrity of the blood vessel and the presence of extravascular erythrocytes (haemorrhages). There was an increased presence of eosinophils and other chronic inflammatory types in certain tissues and organs, often in large numbers and associated with microfilarial destruction. Highly vascularized organs like the brain, heart, lungs and kidneys were observed to have more microfilariae in tissue sections. The number of mf seen in the brain and kidneys of animals administered IVM alone tripled that of control animals. Co-administration of IVM + PSE caused a greater increase in mf in the brain and kidneys while the reverse was noticed with the co-administration of IVM + ASA. The treatment of Loa hyper-microfilaraemic individuals with ivermectin produces a clinical spectrum that parallels that seen in Loa hyper-microfilaraemic humans treated with ivermectin. The utilization of this experimental model can contribute to the improved management of the adverse responses in humans

Evinacumab for Homozygous Familial Hypercholesterolemia

BACKGROUND Homozygous familial hypercholesterolemia is characterized by premature cardiovascular disease caused by markedly elevated levels of low-density lipoprotein (LDL) cholesterol. This disorder is associated with genetic variants that result in virtually absent (null–null) or impaired (non-null) LDL-receptor activity. Loss-offunction variants in the gene encoding angiopoietin-like 3 (ANGPTL3) are associated with hypolipidemia and protection against atherosclerotic cardiovascular disease. Evinacumab, a monoclonal antibody against ANGPTL3, has shown potential benefit in patients with homozygous familial hypercholesterolemia. METHODS In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned in a 2:1 ratio 65 patients with homozygous familial hypercholesterolemia who were receiving stable lipid-lowering therapy to receive an intravenous infusion of evinacumab (at a dose of 15 mg per kilogram of body weight) every 4 weeks or placebo. The primary outcome was the percent change from baseline in the LDL cholesterol level at week 24. RESULTS The mean baseline LDL cholesterol level in the two groups was 255.1 mg per deciliter, despite the receipt of maximum doses of background lipid-lowering therapy. At week 24, patients in the evinacumab group had a relative reduction from baseline in the LDL cholesterol level of 47.1%, as compared with an increase of 1.9% in the placebo group, for a between-group least-squares mean difference of –49.0 percentage points (95% confidence interval [CI], –65.0 to –33.1; P 0.001); the between-group least-squares mean absolute difference in the LDL cholesterol level was –132.1 mg per deciliter (95% CI, –175.3 to –88.9; P 0.001). The LDL cholesterol level was lower in the evinacumab group than in the placebo group in patients with null–null variants (–43.4% vs. +16.2%) and in those with non-null variants (–49.1% vs. –3.8%). Adverse events were similar in the two groups. CONCLUSIONS In patients with homozygous familial hypercholesterolemia receiving maximum doses of lipid-lowering therapy, the reduction from baseline in the LDL cholesterol level in the evinacumab group, as compared with the small increase in the placebo group, resulted in a between-group difference of 49.0 percentage points at 24 weeks. (Funded by Regeneron Pharmaceuticals; ELIPSE HoFH ClinicalTrials.gov number, NCT03399786.