Long‐term effects of angiotensin II blockade with irbesartan on inflammatory markers in hemodialysis patients: A randomized double blind placebo controlled trial (SAFIR study)

Introduction: Low‐grade chronic inflammation is common in hemodialysis (HD) patients. Previous studies suggest an anti‐inflammatory effect of angiotensin II receptor blocker (ARB) treatment. The aim of this study was to compare the effect of ARB vs. placebo on plasma concentrations of inflammatory markers in HD patients. Methods: Adult HD patients were randomized for double‐blind treatment with the ARB irbesartan 150–300 mg/day or placebo. At baseline, 1 week, 3, 6, 9, and 12 months plasma high sensitivity C‐reactive protein (hsCRP), interleukin (IL)?1β, IL‐6, IL‐8, IL‐18, and transforming growth factor‐β (TGF‐β) were measured using Luminex and enzyme‐linked immunosorbent assay (ELISA) technology. Findings: Eighty‐two patients were randomized (placebo/ARB: 41/41). The groups did not differ in initial levels of any of the inflammatory markers (placebo/ARB median(range)): hsCRP 3.3(0.2–23.4)/2.7(0.2–29.6) μg/mL; IL‐1β 1.1(0.0–45.9)/1.1(0.0‐7.2) pg/mL; IL‐6 10(1–90)/12(1–84) pg/mL; IL‐8 31(9–134)/34(5–192) pg/mL; IL‐18 364(188–1343)/377(213–832) pg/mL; TGF‐β 3.2(0.8–13.9)/3.6(1.3–3.8) ng/mL. Overall, there was no significant difference in hsCRP, IL‐6, IL‐8, and TGF‐β between placebo and ARB‐treated patients during the study period, and hsCRP, IL‐6, IL‐8, and TGF‐β were relatively stable during the study period (P ≥ 0.18 in all tests for parallel curves, equal levels, and constant levels). The IL‐1β level was slightly different in the two groups over time, but not significantly (P = 0.09 in test for parallel curves) and it was also relatively stable during the study period (P ≥ 0.49 in tests for equal levels and constant level). IL‐18 was the only inflammatory marker which was not constant during the study period (P = 0.001 in test for constant level), but there was no significant difference between placebo and ARB‐treated (P ≥ 0.51 in tests for parallel curves and equal levels). Discussion: Inflammatory biomarkers were neither acutely, nor in the long‐term significantly affected by the ARB irbesartan. Our findings suggest that ARB treatment in HD patients does not offer protective anti‐inflammatory effects.     

The Formation of Calcified Nanospherites during Micropetrosis Represents a Unique Mineralization Mechanism in Aged Human Bone

Osteocytes—the central regulators of bone remodeling—are enclosed in a network of microcavities (lacunae) and nanocanals (canaliculi) pervading the mineralized bone. In a hitherto obscure process related to aging and disease, local plugs in the lacuno‐canalicular network disrupt cellular communication and impede bone homeostasis. By utilizing a suite of high‐resolution imaging and physics‐based techniques, it is shown here that the local plugs develop by accumulation and fusion of calcified nanospherites in lacunae and canaliculi (micropetrosis). Two distinctive nanospherites phenotypes are found to originate from different osteocytic elements. A substantial deviation in the spherites' composition in comparison to mineralized bone further suggests a mineralization process unlike regular bone mineralization. Clearly, mineralization of osteocyte lacunae qualifies as a strong marker for degrading bone material quality in skeletal aging. The understanding of micropetrosis may guide future therapeutics toward preserving osteocyte viability to maintain mechanical competence and fracture resistance of bone in elderly individuals.     

The Effects of Debonding on the Low-Velocity Impact Response of Steel-CFRP Fibre Metal Laminates

The effect of metal-composite debonding on low-velocity impact response, i.e. on contact force–central deflection response, deformation profiles and strains on the free surfaces was studied. We focused on type 2/1 fibre metal laminate specimens made of stainless steel and carbon fibre epoxy layers, and tested them with drop-weight impact and quasi-static indentation loadings. Local strains were measured with strain gauges and full-field strains with a 3-D digital image correlation method. In addition, finite element simulations were performed and the effects of debonding were studied by exploiting cohesive elements. Our results showed that debonding, either the initial debonding or that formed during the loading, lowers the slope of the contact force–central deflection curve during the force increase. The debonding formation during the rebound phase was shown to amplify the rebound of the impact side, i.e. to lower the ultimate post-impact deflection. The free surface strains were studied on the laminate’s lower surface at the area outside the debond damage. In terms of in-plane strains, debonding formation during impact and indentation, as well as the initial debonding, lowered the peripheral strain and resulted in a positive change in the radial strain.     

The mitigation hierarchy upside down – a study of nature protection measures in Danish infrastructure projects

This paper presents a Danish study of mitigation directed at nature protection in environmental impact assessment (EIA) of infrastructure projects. The study is based on a document analysis of EIA reports, a workshop held with EIA professionals, and a study of two cases. The paper takes a point of departure in the mitigation hierarchy as a central conceptual framework, identifies which mitigation measures have been suggested in the EIA reports, and compares this to the mitigation hierarchy. Further, the paper explores the dynamics behind which mitigation measures are chosen and later implemented. The findings point to a discrepancy between the prevention principle embedded in the mitigation hierarchy and the actual EIA practice with increased use of nature compensation. Further, the research reveals significant variation in the design of mitigation measures, e.g. in the level of detail used in describing them and the level of clarity as to aims and actions.     

The use of social media in impact assessment: experiences among national infrastructure developers in Denmark

Social media plays an increasingly prominent role in the interaction between impact assessments and society. Impact assessment is thus becoming part of social networks that are claimed to be able to improve interaction between actors in impact assessment processes. By investigating the use of social media in impact assessment and planning processes of national linear infrastructure development, we explore how social media impinge on participatory practices and how the potential of social media is realized in the current use related to public participation processes. The study focuses on experiences among national developers working in road, rail, electricity, gas, and metro infrastructures in Denmark. The article shows that the current use of social media in public participatory practices is limited to branding and on-way communication and that the increasing use of social media in linear infrastructure planning gives rise to a variety of concerns among developers that are related to especially organizational cultures, perception of the target groups, and prioritization of resources.     

Ultralow Expansion Glass as Material for Advanced Micromechanical Systems

Ultralow expansion (ULE) glasses are of special interest for temperature stabilized systems for example in precision metrology. Nowadays, ULE materials are mainly used in macroscopic and less in micromechanical systems. Reasons for this are a lack of technologies for parallel fabricating high-quality released microstructures with a high accuracy. As a result, there is a high demand in transferring these materials into miniaturized application examples, realistic system modeling, and the investigation of microscopic material properties. Herein, a technological base for fabricating released micromechanical structures and systems with a structure height above 100 μm in ULE 7972 glass is established. Herein, the main fabrication parameters that are important for the system design and contribute thus to the introduction of titanium silicate as material for glass-based micromechanical systems are discussed. To study the mechanical properties in combination with respective simulation models, microcantilevers are used as basic mechanical elements to evaluate technological parameters and other impact factors. The implemented models allow to predict the micromechanical system properties with a deviation of only ±5% and can thus effectively support the micromechanical system design in an early stage of development.     

Intradermal and subcutaneous leiomyosarcoma: a clinicopathological and immunohistochemical study of 41 cases

Superficial leiomyosarcomas are rare tumours. The lesions confined to the dermis, contrary to those involving the subcutis, have been reported to carry a favourable prognosis. A retrospective study of 41 consecutive cases of surgically treated intradermal and subcutaneous leiomyosarcomas was undertaken in order to determine the prognostic factors that may influence the survival of these patients. Seven tumours were predominantly intradermal and 34 involved the subcutaneous tissue. Fifty-four percent of the tumours were located in the lower extremities. All cases stained positively for smooth muscle antigen and 66% for desmin. The tumours were classified with regard to tumour grade I (low grade, 3%), II (intermediate, 12%), IIIA (high grade, 46%) and IIIB (high grade, 39%). In all patients, follow-up information was available. Mean follow-up time was 5 years. The patients with intradermal tumours were all alive without signs of recurrence, whereas 14 of those with leiomyosarcomas involving the subcutis have died with pulmonary metastases. Our study confirms that "pure" intradermal leiomyosarcomas independent of tumour grade behave in a benign fashion, probably due to small tumour size. Tumour size > or = 5 cm, deep localization with fascia involvement, and high malignancy grade (IIIB) were found to deteriorate survival based on a univariate analysis. However, in a multivariate analysis only tumour size was found to be an independent prognostic factor.     

Transmission electron microscopy study of a dental gallium alloy

Analytical transmission electron microscopy (TEM) studies of a dental gallium alloy have been carried out. This commercial Ga alloy was made by triturating a Ag-Sn-Cu-rich alloy powder with a liquid Ga alloy containing Ga, In and Sn. Ga alloys are of increasing interest as an alternative to amalgam. The dental material studied in the present work was found to be a composite consisting of remaining, undissolved particles from the Ag-based alloy powder in a matrix of reaction products with the liquid Ga alloy. The phases in the matrix and the remaining Ag-based alloy particles have been identified by electron diffraction, high resolution electron microscopy and energy dispersive X-ray spectroscopy. the following phases were identified: orthorhombic Ag₃Sn, cubic -Cu₉Ga₄, cubic Ag₉In₄, tetragonal -Sn and hexagonal Ag₂Ga. In addition to these well-known phases Ga-rich regions of Cu-Ga were observed consisting of an intergrowth of the tetragonal CuGa₂ and one of the cubic -Cu₉Ga₄ phases.     

Liquidus temperatures for primary crystallization of cryolite in molten salt systems of interest for aluminum electrolysis

Temperatures for primary crystallization of Na₃AlF₆ in multicomponent electrolyte systems of interest for the aluminum electrolysis process were determined by thermal analysis. The results are presented as binary and quasibinary diagrams and discussed in view of the literature data. An empirical equation describing liquidus temperatures for primary crystallization of Na₃AlF₆ was derived: $$\begin{gathered} t/(^\circ C) = 1011 + 0.50[AlF_3 ] - 0.13[AIF_3 ] - \frac{{3.45[CaF_2 ]}}{{1 + 0.0173[CaF_2 ]}} \hfill \\ + 0.124[CaF_2 ] \cdot [AlF_3 ] - 0.00542([CaF_2 ] \cdot [AlF_3 ])^{1.5} \hfill \\ - \frac{{7.93[Al_2 O_3 ]}}{{1 + 0.0936[Al_2 O_3 ] - 0.0017[Al_2 O_3 ]^2 - 0.0023[AlF_3 ] \cdot [Al_2 O_3 ]}} \hfill \\ - \frac{{8.90[LiF]}}{{1 + 0.0047[LiF] + 0.0010[AlF3]^2 }} - 3.95[MgF_2 ] - 3.95 \hfill \\ \end{gathered} $$ wheret is the temperature in degree Celsius and the square brackets denote the weight percent of components in the system Na₃AlF₆-AlF₃-CaF₂-Al₂O₃-LiF-MgF₂-KF. The composition limitations are [AlF₃] ≈ [CaF₂] ≈ [LiF] < 20 wt pct, [MgF₂] ≈ [KF] < 5 wt pct, and [A1₂O₃] up to saturation.     

Specification and refinement of networks of asynchronously communicating agents using the assumption/commitment paradigm

This paper presents an assumption/commitment specification technique and a refinement calculus for networks of agents communicating asynchronously via unbounded FIFO channels in the tradition of Kahn.

We define two types of assumption/commitment specifications, namely simple and general specifications.

It is shown that semantically, any deterministic agent can be uniquely characterized by a simple specification, and any nondeterministic agent can be uniquely characterized by a general specification.

We define two sets of refinement rules, one for simple specifications and one for general specifications. The rules are Hoare-logic inspired. In particular the feedback rules employ invariants in the style of a traditional while-rule.

Both sets of rules have been proved to be sound and also (semantic) relative complete.

Conversion rules allow the two logics to be combined. This means that general specifications and the rules for general specifications have to be introduced only at the point in a system development where they are really needed.