The Influence of Different European Cements on the Transport and Early-age Properties of Concrete in the Cover-zone

The use of in situ tests for performance based specification would require demonstration of their suitability to distinguish the quality of concrete. With the introduction of new European Standards for cements, this would mean concretes produced with these new cements should be classified for their quality using the performance tests. It is generally believed that transport properties of concrete are related to their durability and hence the measurement of these properties can form the basis of performance based specifications. This paper reports data indicating that transport properties measured at 28-days for concretes manufactured with different European cements and water-binder ratios can form the basis of classifying concrete for their durability. The results also demonstrated how the different cements specified in European Standards influence the transport properties and other early-age properties

Preclinical Evaluation of Novel All-in-one Formulations of 5-Fluorouracil and Folinic Acid with Reduced Toxicity Profiles - Supplementary Data

Objectives: 5-Fluorouracil (5-FU) in combination with its synergistic biomodulator folinic acid maintains a pivotal position in cancer chemotherapy. However, clinical limitations persist with the administration of these drugs in combination including phlebitis and catheter blockages, which are associated with reduced efficacy and/or quality of life for patients. We have previously reported novel all-in-one, pH neutral, parenteral 5-FU and folinic acid formulations (termed Fluorodex) incorporating beta-cyclodextrins. Fluorodex maintains potency while overcoming the accepted incompatibility of 5-FU and folinic acid.Methods: We performed toxicological, pharmacokinetic and biodistribution, and efficacy evaluations of Fluorodex compared to 5-FU:folinic acid using several administration routes and schedules in two rodent models. These were compared to dose-matched sequential administration of 5-FU:folinic acid.Results: Fluorodex showed bioequivalence to 5-FU:folinic acid as assessed by tissue distribution and pharmacokinetics of 5-FU, but was generally better tolerated as determined by weight loss, hematological and other clinical parameters. Compared to 5-FU:folinic acid, Fluorodex was also associated with reduced phlebitis using a rabbit ear vein model. Furthermore, equivalent to enhanced efficacy of Fluorodex compared to 5-FU:folinic acid against human carcinoma tumour models in mice was observed.Conclusions: These novel all-in-one formulations represent a superior injectable form of 5- FU that allows co-delivery of folinic acid. This should translate to improved patient tolerability with potential for enhanced efficacy

Developments in Performance Monitoring of Concrete Exposed to Extreme Environments.

The performance of the surface zone of concrete is acknowledged as a major factor governing the rate of deterioration of reinforced concrete structures because it provides the only barrier to the ingress of water containing dissolved ionic species such as chlorides, which ultimately initiate corrosion of the reinforcement. In situ monitoring of cover-zone concrete is therefore critical in attempting to make realistic predictions as to the in-service performance of the structure. To this end, this paper presents developments in a remote interrogation system to allow for continuous, real-time monitoring of the cover-zone concrete from an office setting. Use is made of a multi electrode array embedded within cover-zone concrete to acquire discretized electrical resistivity and temperature measurements, with both parameters monitored spatially and temporally. On-site instrumentation, which allows for the remote interrogation of concrete samples placed at a marine exposure site, is detailed together with data handling and processing procedures. Site measurements highlight the influence of temperature on electrical resistivity and an Arrhenius-based temperature correction protocol is developed using on-site measurements to standardize resistivity data to a reference temperature; this is an advancement over the use of laboratory-based procedures. The testing methodology and interrogation system represent a robust, low-cost, and high-value technique that could be deployed for intelligent monitoring of reinforced concrete structures

P450 oxidoreductase deficiency: A systematic review and meta-analysis of genotypes, phenotypes and their relationships

Context: P450 oxidoreductase deficiency (PORD) is a rare genetic disorder that is associated with significant morbidity. However there has been limited analysis of reported PORD cases. Objective: To determine, based on the cohort of reported PORD cases, genotype-phenotype relationships for skeletal malformations, maternal virilisation in pregnancy, adrenal insufficiency and disorders of sexual development (DSD). Data Sources: PubMed and Web of Science from January 2004 to February 2018. Study Selection: Published case reports/series of patients with PORD. Eligible patients were unique, had biallelic mutations and their clinical features reported. Data Extraction: Patient data were manually extracted from the text of case reports/series. A malformation score, representing the severity of skeletal malformations, was calculated for each patient. Data Synthesis: Of the 211 patients published in the literature, 90 patients were eligible for inclusion. Over 60 unique mutations were identified in this cohort. Four groups of mutations were identified, through regression modelling, as having significantly different skeletal malformation scores. Maternal virilisation in pregnancy, reported for 21% of patients, was most common for R457H mutations. Adrenal insufficiency occurred for the majority of patients (78%) and was typically mild, with homozygous R457H mutations being the least deficient. DSD affected most patients (72%) but were less common for males (46XY) with homozygous R457H mutations. Conclusions: PORD is a complex disorder with many possible mutations affecting a large number of enzymes. By analysing the cohort of reported PORD cases, this study identified clear relationships between genotype and several important phenotypic features

Development of diagnostics for high-energy petawatt pulses

Applications accessed by high energy petawatt (HEPW) lasers require complete, single-shot characterization of pulse spatial, temporal, and energy characteristics. We describe techniques that enable single-shot characterization of the temporal shape and pulse contrast of HEPW pulses with >10{sup 8} dynamic range over a ns-temporal window. Approaches to measure pulse durations that span two orders of magnitude will be discussed. Finally, we describe a novel implementation of spectrally dispersed two-beam interferometry for measurement of the phase difference between two HEPW pulses. This technique can be applied to dispersion and B-integral measurements in a HEPW system, as well as to achieve precise timing of nanosecond pulses. Lastly, spectrally dispersed interferometry represents an ideal technique to enable coherent addition of HEPW pulses for production of ultrahigh intensities

An argument against the focus on Community Resilience in Public Health

Background - It has been suggested that Public Health professionals focus on community resilience in tackling chronic problems, such as poverty and deprivation; is this approach useful? Discussion - Resilience is always i) of something ii) to something iii) to an endpoint, as in i) a rubber ball, ii) to a blunt force, iii) to its original shape. “Community resilience” might be: of a neighbourhood, to a flu pandemic, with the endpoint, to return to normality. In these two examples, the endpoint is as-you-were. This is unsuitable for some examples of resilience. A child that is resilient to an abusive upbringing has an endpoint of living a happy life despite that upbringing: this is an as-you-should-be endpoint. Similarly, a chronically deprived community cannot have the endpoint of returning to chronic deprivation: so what is its endpoint? Roughly, it is an as-you-should-be endpoint: to provide an environment for inhabitants to live well. Thus resilient communities will be those that do this in the face of challenges. How can they be identified? One method uses statistical outliers, neighbourhoods that do better than would be expected on a range of outcomes given a range of stressors. This method tells us that a neighbourhood is resilient but not why it is. In response, a number of researchers have attributed characteristics to resilient communities; however, these generally fail to distinguish characteristics of a good community from those of a resilient one. Making this distinction is difficult and we have not seen it successfully done; more importantly, it is arguably unnecessary. There already exist approaches in Public Health to assessing and developing communities faced with chronic problems, typically tied to notions such as Social Capital. Communityresilience to chronic problems, if it makes sense at all, is likely to be a property that emerges from the various assets in a community such as human capital, built capital and natural capital. Summary - Public Health professionals working with deprived neighbourhoods would be better to focus on what neighbourhoods have or could develop as social capital for living well, rather than on the vague and tangential notion of community resilience.</p

Recognition and diagnosis of sleep disorders in Parkinson's disease

Contains fulltext : 109296.pdf (publisher's version ) (Open Access)Sleep disturbances are among the most frequent and incapacitating non-motor symptoms of Parkinson's disease (PD), and are increasingly recognized as an important determinant of impaired quality of life. Here we review several recent developments regarding the recognition and diagnosis of sleep disorders in PD. In addition, we provide a practical and easily applicable approach to the diagnostic process as a basis for tailored therapeutic interventions. This includes a stepwise scheme that guides the clinical interview and subsequent ancillary investigations. In this scheme, the various possible sleep disorders are arranged not in order of prevalence, but in a 'differential diagnostic' order. We also provide recommendations for the use of sleep registrations such as polysomnography. Furthermore, we point out when a sleep specialist could be consulted to provide additional diagnostic and therapeutic input. This structured approach facilitates early detection of sleep disturbances in PD, so treatment can be initiated promptly

Status of the "ARC", a Quad of High-Intensity Beam Lines at the National Ignition Facility

We present the status of plans to commission a short-pulse, quad of beams on the National Ignition Facility (NIF), capable of generating &gt; 10 kJ of energy in 10 ps. These beams will initially provide an advanced radiographic capability (ARC) to generate brilliant, x-ray back-lighters for diagnosing fuel density and symmetry during ignition experiments. A fiber, mode-locked oscillator generates the seed pulse for the ARC beam line in the NIF master oscillator room (MOR). The 200 fs, 1053 nm oscillator pulse is amplified and stretched in time using a chirped-fiber-Bragg grating. The stretched pulse is split to follow two separate beam paths through the chain. Each pulse goes to separate pulse tweakers where the dispersion can be adjusted to generate a range of pulse widths and delays at the compressor output. After further fiber amplification the two pulses are transported to the NIF preamplifier area and spatially combined using shaping masks to form a split-spatial-beam profile that fits in a single NIF aperture. This split beam propagates through a typical NIF chain where the energy is amplified to several kilojoules. A series of mirrors directs the amplified, split beam to a folded grating compressor that is located near the equator of the NIF target chamber. Figure 1 shows a layout of the beam transport and folded compressor, showing the split beam spatial profile. The folder compressor contains four pairs of large, multi-layer-dielectric gratings; each grating in a pair accepts half of the split beam. The compressed output pulse can be 0.7-50 ps in duration, depending on the setting of the pulse tweaker in the MOR. The compressor output is directed to target chamber center using four additional mirrors that include a 9 meter, off-axis parabola. The final optic, immediately following the parabola, is a pair of independently adjustable mirrors that can direct the pair of ARC beams to individual x-ray backlighter targets. The first mirror after the compressor leaks a small fraction of the light that is transported to a diagnostics station where detailed measurements of the spatial and temporal characteristics of the ARC pulse will be recorded for each shot. A NIF quad of short-pulse beams will support up to eight, independently-timed, short-pulse beams, capable of producing an x-ray motion picture. Alternatively, the combined aperture of the quad can direct &gt; 10 kJ of energy in 10 psec onto a single target, enabling research into fast ignition and high-energy-density science on the NIF. We will discuss modifications to the NIF to accommodate ARC, including features such as simultaneous NIF-ARC operation in the same NIF quad, protection against backward propagating pulses from the target and plans to coherently add split beams