Angiotensin II-induced hypertension in rats is only transiently accompanied by lower renal oxygenation

 This is the final version. Available from Springer Nature via the DOI in this record. Activation of the renin-angiotensin system may initiate chronic kidney disease. We hypothesised that renal hypoxia is a consequence of hemodynamic changes induced by angiotensin II and occurs prior to development of severe renal damage. Male Sprague-Dawley rats were infused continuously with angiotensin II (350 ng/kg/min) for 8 days. Mean arterial pressure (n = 5), cortical (n = 6) and medullary (n = 7) oxygenation (pO2) were continuously recorded by telemetry and renal tissue injury was scored. Angiotensin II increased arterial pressure gradually to 150 ± 18 mmHg. This was associated with transient reduction of oxygen levels in renal cortex (by 18 ± 2%) and medulla (by 17 ± 6%) at 10 ± 2 and 6 ± 1 hours, respectively after starting infusion. Thereafter oxygen levels normalised to pre-infusion levels and were maintained during the remainder of the infusion period. In rats receiving angiotensin II, adding losartan to drinking water (300 mg/L) only induced transient increase in renal oxygenation, despite normalisation of arterial pressure. In rats, renal hypoxia is only a transient phenomenon during initiation of angiotensin II-induced hypertension.British Heart FoundationBritish Heart FoundationDutch Kidney FoundationEuropean Union, Seventh Framework Programm

Criteria for developing, assessing and selecting candidate EQ-5D bolt-ons.

PURPOSE: 'Bolt-on' dimensions are additional items added to multi-attribute utility instruments (MAUIs) such as EQ-5D that measure constructs not included in the core descriptive system. The use of bolt-ons has been proposed to improve the content validity and responsiveness of the descriptive system in certain settings and health conditions. EQ-5D bolt-ons serve a particular purpose and thus satisfy a certain set of criteria. The aim of this paper is to propose a set of criteria to guide the development, assessment and selection of candidate bolt-on descriptors. METHODS: Criteria were developed using an iterative approach. First, existing criteria were identified from the literature including those used to guide the development of MAUIs, the COSMIN checklist and reviews of existing bolt-ons. Second, processes used to develop bolt-ons based on qualitative and quantitative approaches were considered. The information from these two stages was formalised into draft development and selection criteria. These were reviewed by the project team and iteratively refined. RESULTS: Overall, 23 criteria for the development, assessment and selection of candidate bolt-ons were formulated. Development criteria focused on issues relating to i) structure, ii) language, and iii) consistency with the existing EQ-5D dimension structure. Assessment and selection criteria focused on face and content validity and classical psychometric indicators. CONCLUSION: The criteria generated can be used to guide the development of bolt-ons across different health areas. They can also be used to assess existing bolt-ons, and inform their inclusion in studies and patient groups where the EQ-5D may lack content validity

Prospective inventory modelling of emerging chemicals: The case of photonic materials

Prospective life cycle assessment (LCA), or ex-ante LCA, has been defined as an assessment of a product system modeled at a future time, before its commercialization. Such assessments bring the promise of altering emerging technologies in a more environmentally benefitial direction before they become difficult to change. Since the future cannot be known with certainty, prospective modeling need to rely on scenarios of various kinds. However, how to conduct such prospective scenario modeling in practice still has to be clarified. In this study, we have modeled two emerging chemicals that can be used for a technology called photon upconversion, which converts low-energy light into higher-energy light harvestable by solar photovoltaics, thereby increasing their efficiency. Two chemicals currently considered for this purpose are ruthenium bipyridine chloride (RBC) and diphenylanthracene (DPA). These novel, emerging chemicals have not been studied regarding environmental performance before and are consequently not present in any LCA databases. The aim of this study is to present a generic procedure for prospective inventory modeling of emerging chemicals and apply that to the cases of RBC and DPA by developing unit processes for these two chemicals. An industrial synthesis scenario was adopted as our main scenario, reflecting a possible future time when RBC and DPA are produced at an industrial scale. The modeling was conducted in six steps: (1) Identify likely chemical syntheses. (2) Calculate inputs stoichiometrically based on the chemical synthesis reactions. (3) Modify inputs based on available yields for reactants and solvents (e.g. obtained from patents or estimated). (4) Categorize outputs as by-products or waste depending on their likely subsequent fate. (5)Calculate process emissions. (6) Model energy flows. Unit processes for the two emerging chemicals are thusly developed. The procedure is considered particularly strong for estimating inputs and output materials related to the stoichiometric reaction, but weaker regarding the estimation of emissions and energy requrement. Further research into the modeling of energy flows for high-temperature processes is therefore recommended, as well as estimation procedures for emissions from emerging chemicals production

Energy use and climate change improvements of Li/S batteries based on life cycle assessment

We present a life cycle assessment (LCA) study of a lithium/sulfur (Li/S) cell regarding its energy use (in\ua0electricity equivalents, kWhel) and climate change (in kg carbon dioxide equivalents, CO2 eq) with the aim of\ua0identifying improvement potentials. Possible improvements are illustrated by departing from a base case of Li/S\ua0battery design, electricity from coal power, and heat from natural gas. In the base case, energy use is calculated\ua0at 580 kWhel kWh−1 and climate change impact at 230 kg CO2 eq kWh−1 of storage capacity. The main contribution\ua0to energy use comes from the LiTFSI electrolyte salt production and the main contribution to climate\ua0change is electricity use during the cell production stage. By (i) reducing cell production electricity requirement,\ua0(ii) sourcing electricity and heat from renewable sources, (iii) improving the specific energy of the Li/S cell, and\ua0(iv) switching to carbon black for the cathode, energy use and climate change impact can be reduced by 54 and\ua093%, respectively. For climate change, our best-case result of 17 kg CO2 eq kWh−1 is of similar magnitude as the\ua0best-case literature results for lithium-ion batteries (LIBs). The lithium metal requirement of Li/S batteries and\ua0LIBs are also of similar magnitude

Checkpoints are blind to replication restart and recombination intermediates that result in gross chromosomal rearrangements

Replication fork inactivation can be overcome by homologous recombination, but this can cause gross chromosomal rearrangements that subsequently missegregate at mitosis, driving further chromosome instability. It is unclear when the chromosome rearrangements are generated and whether individual replication problems or the resulting recombination intermediates delay the cell cycle. Here we have investigated checkpoint activation during HR-dependent replication restart using a site-specific replication fork-arrest system. Analysis during a single cell cycle shows that HR-dependent replication intermediates arise in S phase, shortly after replication arrest, and are resolved into acentric and dicentric chromosomes in G2. Despite this, cells progress into mitosis without delay. Neither the DNA damage nor the intra-S phase checkpoints are activated in the first cell cycle, demonstrating that these checkpoints are blind to replication and recombination intermediates as well as to rearranged chromosomes. The dicentrics form anaphase bridges that subsequently break, inducing checkpoint activation in the second cell cycle

Cause-specific mortality time series analysis: a general method to detect and correct for abrupt data production changes

<p>Abstract</p> <p>Background</p> <p>Monitoring the time course of mortality by cause is a key public health issue. However, several mortality data production changes may affect cause-specific time trends, thus altering the interpretation. This paper proposes a statistical method that detects abrupt changes ("jumps") and estimates correction factors that may be used for further analysis.</p> <p>Methods</p> <p>The method was applied to a subset of the AMIEHS (Avoidable Mortality in the European Union, toward better Indicators for the Effectiveness of Health Systems) project mortality database and considered for six European countries and 13 selected causes of deaths. For each country and cause of death, an automated jump detection method called Polydect was applied to the log mortality rate time series. The plausibility of a data production change associated with each detected jump was evaluated through literature search or feedback obtained from the national data producers.</p> <p>For each plausible jump position, the statistical significance of the between-age and between-gender jump amplitude heterogeneity was evaluated by means of a generalized additive regression model, and correction factors were deduced from the results.</p> <p>Results</p> <p>Forty-nine jumps were detected by the Polydect method from 1970 to 2005. Most of the detected jumps were found to be plausible. The age- and gender-specific amplitudes of the jumps were estimated when they were statistically heterogeneous, and they showed greater by-age heterogeneity than by-gender heterogeneity.</p> <p>Conclusion</p> <p>The method presented in this paper was successfully applied to a large set of causes of death and countries. The method appears to be an alternative to bridge coding methods when the latter are not systematically implemented because they are time- and resource-consuming.</p

Environmental Assessment of Emerging Technologies: Recommendations for Prospective LCA

The challenge of assessing emerging technologies with life cycle assessment (LCA) has been increasingly discussed in the LCA field. In this article, we propose a definition of prospective LCA: An LCA is prospective when the (emerging) technology studied is in an early phase of development (e.g., small-scale production), but the technology is modeled at a future, more-developed phase (e.g., large-scale production). Methodological choices in prospective LCA must be adapted to reflect this goal of assessing environmental impacts of emerging technologies, which deviates from the typical goals of conventional LCA studies. The aim of the article is to provide a number of recommendations for how to conduct such prospective assessments in a relevant manner. The recommendations are based on a detailed review of selected prospective LCA case studies, mainly from the areas of nanomaterials, biomaterials, and energy technologies. We find that it is important to include technology alternatives that are relevant for the future in prospective LCA studies. Predictive scenarios and scenario ranges are two general approaches to prospective inventory modeling of both foreground and background systems. Many different data sources are available for prospective modeling of the foreground system: scientific articles; patents; expert interviews; unpublished experimental data; and process modeling. However, we caution against temporal mismatches between foreground and background systems, and recommend that foreground and background system impacts be reported separately in order to increase the usefulness of the results in other prospective studies

Water supply of ancient Egyptian settlements: the role of the state. Overview of a relatively equitable scheme from the Old to New Kingdom (ca. 2543-1077 BC).

This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s12685-015-0150-xThe study of the textual and archaeological evidence shows that the water supply of the settlements of ancient Egypt seems to have worked on a simple and a relatively equitable scheme, at least from the Old Kingdom until the New Kingdom (ca. 2543-1077). The water supply of the inhabitants was completely managed by the state, through the local administration which was charged to bring the water, in general from a rural area, into towns and cities and to redistribute it to the inhabitants. The method of supply is illustrated by several sources of evidence, in particular by the well known case of the "water-carriers" of the village of Deir el-Medina. Thus, drawing together text and archaeology, this paper will demonstrate that over an extended period, even when the city was far from a water source, the state did not set up complex installations such as pipe networks or wells to bring water, but preferred a simpler system using the manpower available

Second international round robin for the quantification of serum non-transferrin-bound iron and labile plasma iron in patients with iron-overload disorders

Non-transferrin-bound iron and its labile (redox active) plasma iron component are thought to be potentially toxic forms of iron originally identified in the serum of patients with iron overload. We compared ten worldwide leading assays (6 for non-transferrin-bound iron and 4 for labile plasma iron) as part of an international inter-laboratory study. Serum samples from 60 patients with four different iron-overload disorders in various treatment phases were coded and sent in duplicate for analysis to five different laboratories worldwide. Some laboratories provided multiple assays. Overall, highest assay levels were observed for patients with untreated hereditary hemochromatosis and beta-thalassemia intermedia, patients with transfusion-dependent myelodysplastic syndromes and patients with transfusion-dependent and chelated beta-thalassemia major. Absolute levels differed considerably between assays and were lower for labile plasma iron than for non-transferrin-bound iron. Four assays also reported negative values. Assays were reproducible with high between-sample and low within-sample variation. Assays correlated and correlations were highest within the group of non-transferrin-bound iron assays and within that of labile plasma iron assays. Increased transferrin saturation, but not ferritin, was a good indicator of the presence of forms of circulating non-transferrin-bound iron. The possibility of using non-transferrin-bound iron and labile plasma iron measures as clinical indicators of overt iron overload and/or of treatment efficacy would largely depend on the rigorous validation and standardization of assay