bluuebunny/crossref_metadata_2025 huggingface dataset:
Liver physiological T1rho dynamics associated with age and gender
Authors: Wáng Yì Xiáng J , Deng Min , Lin Jiang , Kwok Anthony WL , Liu Eric KW , Chen Weitian
Published: August 2017

Purpose

Using a single breathhold black blood sequence, the current study aims to understand the physiological ranges of liver T1rho relaxation for women and men.

Materials and Methods

This volunteer study was conducted with institutional ethics committee approval, and included 62 females (age mean: 38.9 years; range: 18-75 years) and 34 males (age mean: 44.7 years, range: 24-80 years). MRI was conducted with a 3.0 T scanner, with six spin-lock times of 0, 10, 20, 25, 35, 50msec and a single breathhold of 12 seconds. Six slices were acquired for each examination.

Results

Female liver T1rho value ranged between 35.07 to 51.97ms, showed an age-dependent decrease with younger women had a higher measurement. Male Liver T1rho values ranged between 34.94 to 43.39 ms, and there was no evidential age-dependence. For females, there was a trend that liver T1rho value could be 4%-5% lower during menstrual phase than nonmenstrual phase. For both females and males, no evidential association was seen between body mass index and liver T1rho.

Conclusion

Liver T1rho physiological value for males have relatively narrow distribution, while physiological value for females have wider distribution, and decreases with age.

Key points

1. Liver T1rho shows an age-dependency in women, with young women showing higher measurement. This age-dependency of liver T1rho measurement is not evidential in men. Post-menopausal women have similar liver T1rho value as men.

2. Women at menstrual phase may have slight lower liver T1rho measurement.

3. No association was noted between body mass index and liver T1rho

4. When blood signal suppression sequence is used, in a population of 62 healthy women and 34 healthy men, the highest measured liver T1rho was 52 msec for young women, 44.7 msec for post-menopausal women, and 43.4 msec for men.
SVclone: inferring structural variant cancer cell fraction
Authors: Cmero Marek , Ong Cheng Soon , Yuan Ke , Schröder Jan , Mo Kangbo ,   PCAWG Evolution and Heterogeneity Working Group, Corcoran Niall M. , Papenfuss Anthony Troy , Hovens Christopher M. , Markowetz Florian , Macintyre Geoff
Published: August 2017

We present SVclone, a computational method for inferring the cancer cell fraction of structural variant breakpoints from whole-genome sequencing data. We validate our approach using simulated and real tumour samples, and demonstrate its utility on 2,778 whole-genome sequenced tumours. We find a subset of liver, breast and ovarian cancer cases with decreased overall survival that have subclonally enriched copy-number neutral rearrangements, an observation that could not be discovered with currently available methods.
T-cell receptor sequencing of early stage breast cancer tumors identifies altered clonal structure of the T-cell repertoire
Authors: Beausang John F. , Wheeler Amanda J. , Chan Natalie H. , Hanft Violet R. , Dirbas Frederick M. , Jeffrey Stefanie S. , Quake Stephen R.
Published: August 2017

Tumor infiltrating T-cells play an important role in many cancers, and can improve prognosis and yield therapeutic targets. We characterized T-cells infiltrating both breast cancer tumors and the surrounding normal breast tissue to identify T-cells specific to each, as well as their abundance in peripheral blood. Using immune profiling of the T-cell beta chain repertoire in 16 patients with early stage breast cancer, we show that the clonal structure of the tumor is significantly different from adjacent breast tissue, with the tumor containing approximately 3-fold more T-cells, but with a lower fraction of unique sequences and higher clonality compared to normal breast. The clonal structure of T-cells in blood and normal breast is more similar than between blood and tumor and can be used to distinguish tumor from normal breast tissue in 14 of 16 patients. Many T-cells overlap between tissues from the same patient, including approximately 50% of T-cells between tumor and normal breast. Both solid tissues contain high-abundance "enriched" sequences that are absent or of low abundance in the other tissue. Many of these T-cells are either not detected or detected with very low frequency in the blood, suggesting the existence of separate compartments of T-cells in both tumor and normal breast. Enriched T-cell sequences are typically unique to each patient, but there is a subset of sequences that are shared between many different patients. We show that most of these are commonly generated sequences and thus unlikely to play an important role in the tumor microenvironment.
A New Mechanism To Identify Cost Savings in NHS Prescribing: Minimising “Price-Per-Unit”
Authors: Croker Richard , Walker Alex J , Bacon Seb , Curtis Helen J , French Lisa , Goldacre Ben
Published: August 2017

Background

Minimising prescription costs while maintaining quality is a core element of delivering high value healthcare. There are various strategies to achieve savings, but almost no research to date on determining the most effective approach. We describe a new method of identifying potential savings due to large national variations in drug cost, including variation in generic drug cost; and compare these with potential savings from an established method (generic prescribing).

Methods

We used English NHS Digital prescribing data, from October 2015 to September 2016. Potential cost savings were calculated by determining the price-per-unit (e.g. pill, ml) for each drug and dose within each general practice. This was compared against the same cost for the practice at the lowest cost decile, to determine achievable savings. We compared these price-per-unit savings to the savings possible from generic switching; and determined the chemicals with the highest savings nationally. A senior pharmacist manually assessed whether a random sample of savings were practically achievable.

Results

We identified a theoretical maximum of £410M of savings over 12 months. £273M of these savings were for individual prescribing changes worth over £50 per practice per month; this compares favorably with generic switching, where only £35M of achievable savings were identified. The biggest savings nationally were on glucose blood testing reagents (£12M), fluticasone propionate (£9M) and venlafaxine (£8M). Approximately half of all savings were deemed practically achievable.

Discussion

We have developed a new method to identify and enable large potential cost savings within NHS community prescribing. Given the current pressures on the NHS, it is vital that these potential savings are realised. Our tool enabling doctors to achieve these savings is now launched in pilot form. However savings could potentially be achieved more simply through national policy change.

Abbreviations

BNF

British National Formulary

CCG

Clinical Commissioning Group

GP

General Practice

MR

Modified Release

NHS

National Health Service

NIC

Net Ingredient Cost

NP8

Non-Part VIII, i.e. drugs not listed in Part VIII of the Drug Tariff

PPU

Price-Per-Unit
Multi-clonal evolution of MDR/XDRM. tuberculosisin a high prevalence setting in Papua New Guinea over three decades
Authors: Bainomugisa Arnold , Lavu Evelyn , Hiashiri Stenard , Majumdar Suman , Honjepari Alice , Moke Rendi , Dakulala Paison , Hill-Cawthorne Grant A. , Sushil Pandey , Marais Ben J. , Coulter Christopher , Coin Lachlan J. M.
Published: August 2017

An outbreak of multi-drug resistant tuberculosis has been reported on Daru Island, Papua New Guinea. TheMycobacterium tuberculosisstrains driving this outbreak and the temporal accrual of drug resistance mutations have not been described. We analyzed 100 isolates using whole genome sequencing and found 95 belonged to a single modern Beijing strain cluster. Molecular dating suggested acquisition of streptomycin and isoniazid resistance in the 1960s, with virulence potentially enhanced by amycP1mutation. The outbreak cluster demonstrated a high degree of co-resistance between isoniazid and ethionamide (80/95; 84.2%) attributed to aninhApromoter mutation combined withinhAandndhcoding mutations. Multidrug resistance (MDR), observed in 78/95 samples, emerged with the acquisition of a typicalrpoBmutation together with a compensatoryrpoCmutation in the 1980s. There was independent acquisition of fluoroquinolone and aminoglycoside resistance; with evidence of local transmission of extensively-drug resistant (XDR) strains from 2009. These findings underscore the importance of whole-genome sequencing in informing an effective public health response to MDR/XDRM. tuberculosis.
NmeCas9 is an intrinsically high-fidelity genome editing platform
Authors: Amrani Nadia , Gao Xin D. , Liu Pengpeng , Edraki Alireza , Mir Aamir , Ibraheim Raed , Gupta Ankit , Sasaki Kanae E. , Wu Tong , Donohoue Paul D. , Settle Alexander H. , Lied Alexandra M. , McGovern Kyle , Fuller Chris K. , Cameron Peter , Fazzio Thomas G. , Zhu Lihua Julie , Wolfe Scot A. , Sontheimer Erik J.
Published: August 2017

Background

The development of CRISPR genome editing has transformed biomedical research. Most applications reported thus far rely upon the Cas9 protein from Streptococcus pyogenes SF370 (SpyCas9). With many RNA guides, wild-type SpyCas9 can induce significant levels of unintended mutations at near-cognate sites, necessitating substantial efforts toward the development of strategies to minimize off-target activity. Although the genome-editing potential of thousands of other Cas9 orthologs remains largely untapped, it is not known how many will require similarly extensive engineering to achieve single-site accuracy within large (e.g. mammalian) genomes. In addition to its off-targeting propensity, SpyCas9 is encoded by a relatively large (~4.2 kb) open reading frame, limiting its utility in applications that require size-restricted delivery strategies such as adeno-associated virus vectors. In contrast, some genome-editing-validated Cas9 orthologs (e.g. from Staphylococcus aureus, Campylobacter jejuni, Geobacillus stearothermophilus and Neisseria meningitidis) are considerably smaller and therefore better suited for viral delivery.

Results

Here we show that wild-type NmeCas9, when programmed with guide sequences of natural length (24 nucleotides), exhibits a nearly complete absence of unintended editing in human cells, even when targeting sites that are prone to off-target activity with wildtype SpyCas9. We also validate at least six variant protospacer adjacent motifs (PAMs), in addition to the preferred consensus PAM (5’-N4GATT-3’), for NmeCas9 genome editing in human cells.

Conclusions

Our results show that NmeCas9 is a naturally high-fidelity genome editing enzyme and suggest that additional Cas9 orthologs may prove to exhibit similarly high accuracy, even without extensive engineering.
Whole chromosome loss in tetraploid cells confers tumorigenic potential in a mouse allograft model
Authors: Thomas Rozario , Marks Daniel H , Chin Yvette , Benezra Robert
Published: August 2017

Whole chromosome gains or losses (aneuploidy) are a hallmark of ~70% of human tumors. Modeling the consequences of aneuploidy has relied on perturbing spindle assembly checkpoint (SAC) components but interpretations of these experiments are clouded by the multiple functions of these proteins. Here we used a Cre recombinase-mediated chromosome loss strategy to individually delete mouse chromosomes 9, 10, 12 or 14 in tetraploid immortalized murine embryonic fibroblasts. While the aneuploid cells generally display a growth disadvantagein vitro, they grow significantly better in low adherence sphere-forming conditions and 3 of the 4 lines are transformedin vivo, forming large and invasive tumors in immunocompromised mice. The aneuploid cells display increased chromosomal instability and DNA damage, a mutator phenotype associated with tumorigenesisin vivo.Thus, these studies demonstrate a causative role for whole chromosome loss in tumorigenesis and may shed light on the early consequences of aneuploidy in mammalian cells.
In situgenome editing method suitable for routine generation of germline modified animal models
Authors: Ohtsuka Masato , Miura Hiromi , Arifin Naomi , Nakamura Shingo , Wada Kenta , Gurumurthy Channabasavaiah B. , Sato Masahiro
Published: August 2017

Animal genome engineering experimental procedures involve three major steps: isolation of zygotes from pregnant females; microinjection of zygotes, and; transfer of injected zygotes into recipient females, that have been practiced for over three decades. The laboratory set ups intending to performing these procedures require to have sophisticated equipment as well as highly skilled technical personnel. Because of these reasons, animal transgenesis experiments are typically performed at centralized core facilities in most research organizations. We recently showed that all three steps, of animal transgensis, can be bypassed using a method termed GONAD (Genome-editing viaOviductalNucleicAcidsDelivery), by directly electroporating genome editing components into zygotesin situ. Although our first report demonstrated the genome-editing capability, its efficiency was lower than the standard methods using microinjection. Here we investigated critical parameters of GONAD to make it suitable for creating animal models of large genomic deletions, single nucleotide corrections and long sequence insertions. The efficiency of genome editing in the improved GONAD (i-GONAD) method reached to the levels comparable to traditional microinjection methods. The streamlined parameters, and the simplified experimental steps, in thei-GONAD method makes it suitable for routine genome editing applications performed both at centralized facilities as well as at the laboratories that lack highly skilled personnel and the sophisticated equipment.
Modulation of host learning inAedes aegyptimosquitoes
Authors: Vinauger Clément , Lahondère Chloé , Wolff Gabriella H. , Locke Lauren T. , Liaw Jessica E. , Parrish Jay Z. , Akbari Omar S. , Dickinson Michael H. , Riffell Jeffrey A.
Published: August 2017

How mosquitoes determine which individuals to bite has important epidemiological consequences. This choice is not random; most mosquitoes specialize in one or a few vertebrate host species, and some individuals in a host population are preferred over others. Here we show that aversive olfactory learning contributes to mosquito preference both between and within host species. Combined electrophysiological and behavioural recordings from tethered flying mosquitoes demonstrated that these odours evoke changes in both behaviour and antennal lobe (AL) neuronal responses. Using electrophysiological and behavioural approaches, and CRISPR gene editing, we demonstrate that dopamine plays a critical role in aversive olfactory learning and modulating odour-evoked responses in AL neurons. Collectively, these results provide the first experimental evidence that olfactory learning in mosquitoes can play an epidemiological role.
The RNA-binding site of poliovirus 3C protein doubles as a phosphoinositide-binding domain
Authors: Shengjuler Djoshkun , Chan Yan Mei , Sun Simou , Moustafa Ibrahim M. , Li Zhen-Lu , Gohara David W. , Buck Matthias , Cremer Paul S. , Boehr David D. , Cameron Craig E.
Published: August 2017

Some viruses use phosphatidylinositol phosphate (PIP) to mark membranes used for genome replication or virion assembly. PIP-binding motifs of cellular proteins do not exist in viral proteins. Molecular-docking simulations revealed a putative site of PIP binding to poliovirus (PV) 3C protein that was validated using NMR spectroscopy. The PIP-binding site was located on a highly dynamic α-helix that also functions in RNA binding. Broad PIP-binding activity was observed in solution using a fluorescence polarization assay or in the context of a lipid bilayer using an on-chip, fluorescence assay. All-atom molecular dynamics simulations of the 3C protein-membrane interface revealed PIP clustering and perhaps PIP-dependent conformations. PIP clustering was mediated by interaction with residues that interact with the RNA phosphodiester backbone. We conclude that 3C binding to membranes will be determined by PIP abundance. We suggest that the duality of function observed for 3C may extend to RNA-binding proteins of other viruses.
Tolerance to hypothermic and antinoceptive effects of Δ9-tetrahydrocannabinol (THC) vapor inhalation in rats
Authors: Nguyen Jacques D. , Grant Yanabel , Kerr Tony M. , Gutierrez Arnold , Cole Maury , Taffe Michael A.
Published: August 2017

Rationale

A reduced effect of a given dose of Δ9-tetrahydrocannabinol (THC) emerges with repeated exposure to the drug. This tolerance can vary depending on THC dose, exposure chronicity and the behavioral or physiological measure of interest. A novel THC inhalation system based on e-cigarette technology has been recently shown to produce the hypothermic and antinociceptive effects of THC in rats.

Objective

To determine if tolerance to these effects can be produced with repeated vapor inhalation.

Methods

Groups of male and female Wistar rats were exposed to 30 minutes of inhalation of the propylene glycol (PG) vehicle or THC (200 mg/mL in PG) two or three times per day for four days. Rectal temperature changes and nociception were assessed after the first exposure on the first and fourth days of repeated inhalation.

Results

Female, but not male, rats developed tolerance to the hypothermic and antinociceptive effects of THC after four days of twice-daily THC vapor inhalation. Thrice daily inhalation for four days resulted in tolerance in both male and female rats. The plasma THC levels reached after a 30 minute inhalation session did not differ between the male and female rats.

Conclusions

Repeated daily THC inhalation induces tolerance in female and male rats, providing further validation of the vapor inhalation method for preclinical studies.

Abbreviations

PG, propylene glycol; THC; Δ9tetrahydrocannabinol;
DeepATAC: A deep-learning method to predict regulatory factor binding activity from ATAC-seq signals
Authors: Hiranuma Naozumi , Lundberg Scott , Lee Su-In
Published: August 2017

Determining the binding locations ofregulatory factors, such as transcription factors and histone modifications, is essential to both basic biology research and many clinical applications. Obtaining such genome-wide location maps directly is often invasive and resource-intensive, so it is common to impute binding locations from DNA sequence or measures of chromatin accessibility. We introduce DeepATAC, a deep-learning approach for imputing binding locations that uses both DNA sequence and chromatin accessibility as measured by ATAC-seq. DeepATAC significantly outperforms current approaches such as FIMO motif predictions overlapped with ATAC-seq peaks, and models based only on DNA sequence, such as DeepSEA. Visualizing the input importances for the DeepATAC model reveals DNA sequence motifs and ATAC-seq signal patterns that are important for predicting binding events. The Keras implementation and analysis pipelines of DeepATAC are available athttps://github.com/hiranumn/deepatac.
Geobacter sulfurreducensextracellular multiheme cytochrome PgcA facilitates respiration to Fe(III) oxides but not electrodes
Authors: Zacharoff Lori , Morrone Dana , Bond Daniel R.
Published: August 2017

Extracellular cytochromes are hypothesized to facilitate the final steps of electron transfer between the outer membrane of the metal-reducing bacteriumGeobacter sulfurreducensand solid-phase electron acceptors such as metal oxides and electrode surfaces during the course of respiration. The trihemec-type cytochrome PgcA exists in the extracellular space ofG. sulfurreducens, and is one of many multihemec-type cytochromes known to be loosely bound to the bacterial outer surface. Deletion ofpgcAusing a markerless method resulted in mutants unable to transfer electrons to Fe(III) and Mn(IV) oxides; yet the same mutants maintained the ability to respire electrode surfaces and soluble Fe(III) citrate. When expressed and purified fromShewanella oneidensis, PgcA demonstrated a primarily alpha helical structure, three bound hemes, and was processed into a shorter 41 kDa form lacking the lipodomain. Purified PgcA bound Fe(III) oxides, but not magnetite, and when PgcA was added to cell suspensions ofG. sulfurreducens,PgcA accelerated Fe(III) reduction similar to addition of FMN. Addition of soluble PgcA to ∆pgcAmutants also restored Fe(III) reduction. This report highlights a distinction between proteins involved in extracellular electron transfer to metal oxides and poised electrodes, and suggests a specific role for PgcA in facilitating electron transfer at mineral surfaces.
Mouse MRI shows brain areas larger in males emerge earlier than those larger in females
Authors: Qiu Lily R. , Fernandes Darren J. , Szulc Kamila U. , Dazai Jun , Nieman Brian J. , Turnbull Daniel H. , Palmert Mark R. , Lerch Jason P.
Published: August 2017

2

Sex differences exist in behaviours, disease and neuropsychiatric disorders. Sexual dimorphisms however, have yet to be studied across the whole brain and across a comprehensive time course of postnatal development. We used manganese-enhanced MRI (MEMRI) to longitudinally image male and female C57BL/6J mice across 9 time points, beginning at postnatal day 3. We recapitulated findings on canonically dimorphic areas, demonstrating the ability of MEMRI to study neuroanatomical sex differences. We discovered, upon whole-brain volume correction, that neuroanatomical regions larger in males develop early in life, while regions larger in females develop in peripubertal life. Furthermore, we found groups of areas with shared sexually dimorphic developmental trajectories that reflect behavioural and functional networks, and expression of genes involved with sex processes. Our results demonstrate the ability of MEMRI to reveal comprehensive developmental differences between male and female brains, which will improve our understanding of sex-specific predispositions to various neuropsychiatric disorders.
Mutualism between microbial populations in structured environments: the role of geometry in diffusive exchanges
Authors: Peaudecerf François J. , Bunbury Freddy , Bhardwaj Vaibhav , Bees Martin A. , Smith Alison G. , Goldstein Raymond E. , Croze Ottavio A.
Published: August 2017

The exchange of diffusive metabolites is known to control the spatial patterns formed by microbial populations, as revealed by recent studies in the laboratory. However, the matrices used, such as agarose pads, lack the structured geometry of many natural microbial habitats, including in the soil or on the surfaces of plants or animals. Here we address the important question of how such geometry may control diffusive exchanges and microbial interaction. We model mathematically mutualistic interactions within a minimal unit of structure: two growing reservoirs linked by a diffusive channel through which metabolites are exchanged. The model is applied to study a synthetic mutualism, experimentally parameterised on a model algal-bacterial co-culture. Analytical and numerical solutions of the model predict conditions for the successful establishment of remote mutualisms, and how this depends, often counterintutively, on diffusion geometry. We connect our findings to understanding complex behaviour in synthetic and naturally occurring microbial communities.
DACH1 stimulates shear stress-guided endothelial cell migration and coronary artery growth through the CXCL12–CXCR4 signaling axis
Authors: Chang Andrew H. , Raftrey Brian C. , D'Amato Gaetano , Surya Vinay N. , Poduri Aruna , Chen Heidi I. , Goldstone Andrew B. , Woo Joseph , Fuller Gerald G. , Dunn Alexander R. , Red-Horse Kristy
Published: August 2017

Sufficient blood flow to tissues relies on arterial blood vessels, but the mechanisms regulating their development are poorly understood. Many arteries, including coronary arteries of the heart, form through remodeling of an immature vascular plexus in a process triggered and shaped by blood flow. However, little is known about how cues from fluid shear stress are translated into responses that pattern artery development. Here, we show that mice lacking endothelial Dach1 had small coronary arteries, decreased endothelial cell polarization, and reduced expression of the chemokine Cxcl12. Under shear stress in culture, Dach1 overexpression stimulated endothelial cell polarization and migration against flow, which was reversed upon CXCL12/CXCR4 inhibition. In vivo, DACH1 was expressed during early arteriogenesis but was down in mature arteries. Mature artery-type shear stress (high, uniform laminar) specifically down-regulated DACH1, while the remodeling artery-type flow (low, variable) maintained DACH1 expression. Together, our data support a model in which DACH1 stimulates coronary artery growth by activating Cxcl12 expression and endothelial cell migration against blood flow into developing arteries. This activity is suppressed once arteries reach a mature morphology and acquire high, laminar flow that down-regulates DACH1. Thus, we identified a mechanism by which blood flow quality balances artery growth and maturation.
Brexit: measuring the impact upon skilled labour in the UK construction industry
Authors: Mohamed Marwan , Pärn Erika Anneli , Edwards David John
Published: August 2017

Purpose

The purpose of this paper is to present an understanding of the potential impact of Brexit upon the UK construction industry. Specifically, the work analyses the construction industry’s reliance upon European Union (EU) skilled labour and seeks to determine the potential impact that Brexit poses upon EU skilled labour entering the sector.

Design/methodology/approach

A perceptual questionnaire survey was used to elicit responses from construction professionals using the two techniques of opportunity and snowballing non-probability sampling. Summary statistical analysis of Boolean and Likert item scale data accrued was employed to elucidate upon respondents’ perceptions.

Findings

The majority of survey participants either “strongly agreed” or “agreed” that the UK construction industry relies upon EU skilled labour and that a career in the sector would not be attractive for foreign skilled labour post-Brexit. Future research proposed includes: predicting future trends in labour supply and demand and deriving new policies to address skills shortage imbalances that may be created by Brexit.

Originality/value

Original insight into an historic and unprecedented moment for the UK construction industry is presented. The work also provides pragmatic recommendations to policy makers and Higher Education Institutes to prevent the risk of Brexit further exacerbating skilled labour shortages within the industry.
Electricity sector’s contribution to greenhouse gas concentration in Nigeria
Authors: Odewale Stephen Ayodele , Sonibare Jacob Ademola , Jimoda Lukuman Adekilekun
Published: August 2017

Purpose

Recent developments in the electricity generation sector of Nigeria necessitated the re-assessment of its contribution to air emission level in the country as information provided by previous inventory is nearly out-of-date. The purpose of this paper is to quantify the carbon dioxide (CO2) emissions generated from existing thermal power plants in the country.

Design/methodology/approach

Thermal power plants in Nigeria and their installed capacities were identified, and estimation of CO2emission from each of the plants was carried out using the emission factor method. In addition to the direct emissions generated through the combustion operation of the power plants, indirect emissions resulting from upstream activities such as extraction, production, and transportation of fuels consumed by the thermal power plant was determined using the same method.

Findings

In total, 40 thermal power plants are currently operational in Nigeria. Additional 18 thermal plants are at different stages of completion. The operational thermal plants have average generation output of 40 percent of their installed capacity and produce 87.3 million metric tonne (mmt)/annum CO2emissions. In total, 66.9 percent of the estimated emissions are direct emissions, i.e. fuel combustion emissions; the rest are indirect emissions. Additional 67.9 mmt was estimated as expected overall emissions from the thermal power plants under construction. Considering the global warming potential of CO2, proactive measures must be taken to regulate its emissions from the country’s thermal power plants.

Originality/value

This paper bridged the information gap existing in the emission inventory from the Nigeria electricity sector by providing up-to-date data on the contribution of the sector to greenhouse gas emission level in the country.
Potential uses of waste sludge in concrete production
Authors: Ramirez Kleber Gomes , Possan Edna , Dezen Bianca Gabriel dos Santos , Colombo Mauricio
Published: August 2017

Purpose

The purpose of this paper is to address the use of sludge from water treatment plant (WTP sludge), in its natural form (wet), in the construction industry, especially in the production of concrete, evaluating the effects of replacing natural sand with different WTP sludge levels in the concrete properties.

Design/methodology/approach

The dosage study evaluated mixtures with replacement levels of 0, 5, 7 and 10 percent of wet sludge in relation to the mass of natural sand, analyzing their effects on mechanical properties and water absorption in concrete with water/cement (w/c) ratios of 0.45, 0.55 and 0.65.

Findings

From the results obtained, it is possible to note that the addition of WTP sludge in its natural form (wet) reduces the strength of concrete. However, from a technical point of view, a level of replacement of up to 5 percent for applications in concrete is suitable, provided that it is not structural concrete.

Practical implications

Further studies should be conducted to verify the influence of the replacement of sand for heat-treated sludge in concrete properties, also analyzing the environmental viability linked to the calcination process.

Originality/value

Few studies are conclusive in relation to the use of WTP sludge in concrete production. This study shows statistically the negative effect of the addition of wet sludge in the mechanical properties and in the water absorption of concretes from different w/c ratios.
Low vs. high haemoglobin trigger for transfusion in vascular surgery: protocol for a randomised trial
Authors: Møller A. , Nielsen H. B. , Wetterslev J. , Pedersen O. B. , Hellemann D. , Shahidi S.
Published: August 2017

Background

In patients with cardiovascular disease, guidelines for administration of red blood cells (RBC) are mainly based on studies outside the vascular surgical setting with the recommendation to use a haemoglobin (hb) trigger‐level lower than by guidelines from The European Society for Vascular Surgery. Restricting RBC transfusion may affect blood O2 transport with a risk for development of tissue ischaemia and postoperative complications.

Methods

In a single‐centre, open‐label, assessor blinded trial, 58 vascular surgical patients (> 40 years of age) awaiting open surgery of the infrarenal aorta or infrainguinal arterial bypass surgery undergo a web‐based randomisation to one of two groups: perioperative RBC transfusion triggered by hb < 8 g/dl or hb < 9.7 g/dl. Administration of fluid follows an individualised strategy by optimising cardiac stroke volume and near‐infrared spectroscopy determines tissue oxygenation. Serious adverse event rates are: myocardial injury (troponin‐I ≥ 45 ng/l or ischaemic electrocardiographic findings at day 30), acute kidney injury, death, stroke and severe transfusion reactions. A follow‐up visit takes place 30 days after surgery and a follow‐up of serious adverse events in the Danish National Patient Register within 90 days is pending.

Discussion

This trial is expected to determine whether a RBC transfusion triggered by hb < 9.7 g/dl compared with hb < 8 g/dl results in adequate separation of postoperative hb levels, transfusion of more RBC units and maintains a higher tissue oxygenation. The results will inform the design of a multicentre trial for evaluation of important postoperative outcomes.
Dyrk1 inhibition improves Alzheimer's disease‐like pathology
Authors: Branca Caterina , Shaw Darren M. , Belfiore Ramona , Gokhale Vijay , Shaw Arthur Y. , Foley Christopher , Smith Breland , Hulme Christopher , Dunckley Travis , Meechoovet Bessie , Caccamo Antonella , Oddo Salvatore
Published: August 2017

There is an urgent need for the development of new therapeutic strategies for Alzheimer's disease (AD). The dual‐specificity tyrosine phosphorylation‐regulated kinase‐1A (Dyrk1a) is a protein kinase that phosphorylates the amyloid precursor protein (APP) and tau and thus represents a link between two key proteins involved in AD pathogenesis. Furthermore, Dyrk1a is upregulated in postmortem human brains, and high levels of Dyrk1a are associated with mental retardation. Here, we sought to determine the effects of Dyrk1 inhibition on AD‐like pathology developed by 3xTg‐AD mice, a widely used animal model of AD. We dosed 10‐month‐old 3xTg‐AD and nontransgenic (NonTg) mice with a Dyrk1 inhibitor (Dyrk1‐inh) or vehicle for eight weeks. During the last three weeks of treatment, we tested the mice in a battery of behavioral tests. The brains were then analyzed for the pathological markers of AD. We found that chronic Dyrk1 inhibition reversed cognitive deficits in 3xTg‐AD mice. These effects were associated with a reduction in amyloid‐β (Aβ) and tau pathology. Mechanistically, Dyrk1 inhibition reduced APP and insoluble tau phosphorylation. The reduction in APP phosphorylation increased its turnover and decreased Aβ levels. These results suggest that targeting Dyrk1 could represent a new viable therapeutic approach for AD.
Initial Clinical Experiences With Novel Diagonal ECLS System in Pediatric Cardiac Patients
Authors: Okan Yildiz , Sertac Haydin , Erkut Ozturk , Taner Kasar , Selen Onan I. , Firat Altin H. , Nihat Cine , Pelin Ayyildiz , Halime Erkan , Alper Guzeltas
Published: August 2017

Extracorporeal life support (ECLS) provides mechanical support following cardiac surgery when respiratory or cardiac failure occurs. The aim of this study was to analyze the safety and feasibility of the Medos Deltastream diagonal pump (DP3) ECLS system in pediatric cardiac patients. We described the technical considerations and risk factors related to the survival outcomes in 102 pediatric cardiac patients who received ECLS support between March 2011 and April 2016. We switched from the DP2 system, which was used for the initial 25 patients, to the DP3 system after November 2012. The DP3 was then used in a consecutive series of 77 patients (4.5% of all pediatric patients who underwent congenital heart surgery during the same time period). The patients’ median age was 90 days (range: 2 days–12 years), while their median weight was 4 kg (range: 2.1–40 kg). Fifty four patients (70%) were weaned off ECLS, while 28 patients (36.3%) were successfully discharged from the hospital by means of the DP3 system. The median ECLS duration for survivors was 8.2 days (range: 4–14.5 days). The ECLS indications, durations, and initiation times had no statistical significance in terms of survival. Renal, hemorrhagic, and neurologic complications were all associated with decreased hospital discharge rates (P = 0.003, P = 0.045, and P < 0.001 respectively). Higher lactate levels (P = 0.009) and longer duration for normalization (P < 0.001) were both associated to failure to wean off ECLS support and, hence, to hospital deaths. The weaning rate was 36% prior to November 2012. It increased to 70.3% after that time (P = 0.009). The mechanical complication rate was 9% with the DP3 system and 32% with the DP2, which was statistically significant (P = 0.009). Additionally, the lactate levels were higher and decreased more slowly in the patients supported by the DP2. As a result of the shift to the DP3 system, a revised ECLS protocol, and increased ECLS experience, a significant improvement was observed in our clinical outcomes. The results of this study suggested that the combination of a DP3 pump and a Hilite oxygenator in pediatric ECLS circuits may improve durability and reduce circuit‐induced complications.
Therapeutic drug monitoring was helpful in guiding the decision‐making process for children receiving infliximab for inflammatory bowel disease
Authors: Deora Vini , Kozak Justin , El‐Kalla Mohamed , Huynh Hien Q. , El‐Matary Wael
Published: August 2017

Aim

This study examined the impact of therapeutic drug monitoring (TDM) on clinical decision‐making for children receiving infliximab for inflammatory bowel disease (IBD).

Methods

The medical records of children with IBD who had infliximab trough levels (ITLs) measured between January 2013 and December 2015 at two Canadian tertiary‐care centres were examined. The indications for TDM, clinical and laboratory disease activity indices and TDM‐driven treatment changes to infliximab therapy were documented.

Results

We included 107 consecutive serum measurements of ITLs in 73 children (40 boys), with a median age of 16.1 years, including 52 with Crohn's disease. TDM was performed due to concerns about clinical disease activity in 24/107 (22.4%) measurements and 83 (77.6%) were ordered as routine tests. Of these, 38 (35.5%) ITLs were suboptimal (<3.5 μg/mL) and 36 (34.0%) resulted in more frequent doses of infliximab, with subsequent improvements in disease biomarkers. Interval changes were implemented as a result of 34 (32.0%) ITLs, with shorter intervals in 19 (17.0%) cases, and seven (6.5%) ITLs resulted in adding or increasing doses of immunomodulators. In addition, four children were switched to adalimumab.

Conclusion

Therapeutic drug monitoring was helpful in guiding the decision‐making process for children with IBD on infliximab.
‘I didn't mean that: It was just a slip of the tongue’: Racial slips and gaffes in the public arena
Authors: Burford‐Rice Rose , Augoustinos Martha
Published: August 2017

Speech errors, slips, and gaffes made in the public arena that are perceived to be either implicitly or explicitly racially offensive often result in significant social consequences to the responsible speaker and generate public controversy. The current research, informed by conversation analysis and discursive psychology, examines how speakers manage such troubles‐in‐speaking in public settings. The sample of naturalistic data includes five such instances and related apologies sourced from YouTube and news websites. The analysis examined how speakers initiated repairs when making offensive racial slips and gaffes and followed these up with apologies. Self‐detected transgressions were repaired in fewer turns than other‐detected blunders. Speakers accounted for their transgressions as innocent mishaps (e.g., ‘it was just a slip of the tongue’, ‘an honest mistake’) to fend off attributions of prejudice or a racist identity. Thus, a common resource that speakers drew upon to exonerate themselves was that what they said, did not align with their psychological intentions. Intention then was a notable psychological resource for denying and fending off attributions of prejudice. Follow‐up apologies were related organizationally and worked to either address or decrease the likelihood of dispreferred responses from the public/audience. These apologies included the use of affect, graduation, amplification, and judgements of capacity. Although this research does not address the possible psychological nature of racial slips and gaffes – the question of what they really mean – their occurrence in everyday life and institutional settings suggest that their repressive qualities reflect shared patterns of understanding in societies structured by racial inequality.
Children's Counterfactual Reasoning About Causally Overdetermined Events
Authors: Nyhout Angela , Henke Lena , Ganea Patricia A.
Published: August 2017

In two experiments, one hundred and sixty‐two 6‐ to 8‐year‐olds were asked to reason counterfactually about events with different causal structures. All events involved overdetermined outcomes in which two different causal events led to the same outcome. In Experiment 1, children heard stories with either an ambiguous causal relation between events or causally unrelated events. Children in the causally unrelated version performed better than chance and better than those in the ambiguous condition. In Experiment 2, children heard stories in which antecedent events were causally connected or causally disconnected. Eight‐year‐olds performed above chance in both conditions, whereas 6‐year‐olds performed above chance only in the connected condition. This work provides the first evidence that children can reason counterfactually in causally overdetermined contexts by age 8.
The role of environmental exposure to peanut in the development of clinical allergy to peanut
Authors: Foong R.X. , Brough H.
Published: August 2017

The prevalence of peanut allergy has increased over the years and still remains one of the most common causes of food‐related anaphylaxis. The way in which peanut sensitization occurs has been explored, such as via maternal consumption in pregnancy, via breastmilk and through a disrupted skin barrier. It has previously been shown that environmental exposure to aeroallergens in household dust can be a risk factor for the development of allergic asthma. There is an increasing body of evidence that the combination of cutaneous sensitization via a disrupted skin barrier (ie children with eczema or with filaggrin mutations) and environmental peanut exposure influences the development of peanut allergy. This review aims to explore routes of peanut sensitization and the current evidence on how environmental exposure to peanut affects the development of peanut allergy.
Impact of preoperative cardiology consultation prior to intermediate‐risk surgical procedures
Authors: Dogan Volkan , Biteker Murat , Özlek Eda , Özlek Bülent , Başaran Özcan , Yildirim Birdal , Kayataş Kadir , Çelik Oğuzhan , Doğan Marwa M.
Published: August 2017

Background

Patients undergoing noncardiac, nonvascular surgery (NCNVS) are at risk of perioperative cardiovascular events. However, benefits of cardiology consultation (CC) in patients with known or suspected cardiac disease undergoing intermediate‐risk NCNVS is unknown.

Methods

The study group included 700 consecutive patients referred for CC before intermediate‐risk NCNVS in a tertiary‐care teaching hospital. The control group included 1200 age‐matched and sex‐matched consecutive patients proceeded to the intermediate‐risk surgery without preoperative CC during the same period. Patients older than 18 years who underwent an elective, NCNVS were enrolled. Requests for consultation were made either by surgeon or an attending anaesthesiologist. All patients underwent a complete preoperative clinical evaluation.

Results

Of the 700 patients who were referred for CC in the study group, 530 patients (75.7%) had no additional recommendations, and 170 patients (24.3%) underwent additional preoperative tests or had a change in preoperative therapy. Only 20 (2.8%) patients’ NCNVS were delayed based on the cardiologists’ recommendation and 680 patients eventually had their surgeries. Major cardiovascular and noncardiovascular complication rates were similar in the study and in the control groups (12.9% vs 13.6%, P = 0.273 and 25.2% vs 26%, P = 0.432 respectively).

Conclusions

Preoperative CC in patients who underwent intermediate‐risk NCNVS does not affect either perioperative management or outcome of surgery.
Anti‐sulfatide/galactocerebroside antibodies in immunoglobulin M paraproteinemic neuropathies
Authors: Boso F. , Ruggero S. , Giannotta C. , Benedetti L. , Marfia G. A. , Ermani M. , Campagnolo M. , Salvalaggio A. , Gallia F. , De Michelis C. , Visentin A. , Bianco M. , Ruiz M. , Mataluni G. , Nobile‐Orazio E. , Briani C.
Published: August 2017

Background and purpose

Anti‐sulfatide antibodies have been observed in heterogeneous neuropathies and their clinical relevance is still controversial. Whether the combination of sulfatide with galactocerebroside would increase sensitivity or specificity of enzyme‐linked immunosorbent assay testing compared to sulfatide alone was assessed.

Methods

Immunoglobulin M (IgM) antibodies to sulfatides, galactocerebroside and combined sulfatide and galactocerebroside (Sulf/GalC) were measured in 229 neuropathy patients, including 73 with IgM paraproteinemic neuropathy [62 with anti‐myelin‐associated glycoprotein (anti‐MAG) antibody] and 156 with other neuropathies. Results from 27 patients with IgM monoclonal gammopathy without neuropathy and 28 healthy subjects served as control.

Results

Thirty‐three patients showed increased titers of anti‐sulfatide antibodies, 28 of whom had an IgM paraproteinemic neuropathy (P < 0.0001). When evaluating the reactivity for the combination Sulf/GalC, 57/229 patients were found to be positive, including 36/73 (49%) with IgM paraproteinemic neuropathy (P < 0.0001). Patients with known anti‐sulfatide antibodies also showed anti‐Sulf/GalC reactivity, with increased titers in 48.5% of the cases. Testing for anti‐Sulf/GalC antibodies allowed 24 additional patients to be detected (eight with IgM paraproteinemic neuropathies), who had no reactivity to the individual glycolipids. Amongst the 11 subjects with IgM paraproteinemic neuropathy who were negative for anti‐MAG antibodies, only two were reactive to sulfatide, whilst six (55%) were found to be positive when tested against the combination of sulfatide and galactocerebroside.

Conclusions

Testing for both sulfatide and galactocerebroside in IgM paraproteinemic neuropathies seems to increase the sensitivity compared to anti‐sulfatide antibodies alone (49% and 39%, respectively, with a slightly reduced specificity, from 97% to 87%), helping the characterization of otherwise undefined neuropathy that could benefit from immunomodulatory therapy.
Effect of maleic acid on the bond strength of fibre posts to root dentine
Authors: Fan Fan , Ibrahim Muhammad , Dai Panpan , Mao Yixin , He Bing , Wu Gang , Ma Jianfeng , Huang Shengbin
Published: August 2017

The aim of this study was to evaluate the effect of maleic acid (MA) on both the bond strength of fibre post to root dentine and smear layer removal after post space preparation. Sixty, single‐canal premolars were endodontically treated and randomly assigned to four groups: group 1 [0.9% saline solution (control]); group 2 [2.5% sodium hypochlorite (NaOCl)]; group 3 [17% ethylenediaminetetraacetic acid (EDTA) followed by 2.5% NaOCl]; and group 4 (7% MA followed by 2.5% NaOCl). Self‐adhesive resin cement was used to test the adhesion of a glass‐fibre post to the root dentine through a micropush‐out test. Scanning electron microscopy was performed to examine and score the treated specimens for smear layer removal, and stereomicroscopy was applied to investigate the failure modes of fibre posts. Maleic acid exhibited the highest mean bond‐strength values in the apical regions among all the groups. Most failure modes (31.9%) were adhesive‐type failures between the dentine and luting materials. Maleic acid performed statistically significantly better than the other groups regarding smear layer removal, especially in the apical region. Maleic acid is an effective irrigant that can remove the smear layer, open dentinal tubules, and act as a high‐efficiency final irrigant in activation protocols.