bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation of multifarious power transferred through the transmission network for all associated generators in the system individually
Authors: Bhowmik Debashish , Sinha Nidul , Sinha Ashoke Kumar
Published: December 2017

In a modern interconnected power system, it is challenging to estimate the amount of power delivered to loads through the transmission lines due to the individual associated generator. This study presents a mathematical approach which helps in the development of an important tool viz. power contribution coefficient, via which the share of power generated from an individual generator and delivered to the rest of the power system network has been traced efficiently. The proposed method presents a modest and spontaneous way of resolving real and reactive power flows through the transmission network due to all associated generators separately. It also gives the contribution of the individual generator to overall system losses and individual load distribution. To clarify the approach, the resolution of a sample case is provided using the proposed method. The performance of the developed technique has been investigated on IEEE 14‐bus test system. To validate the method, the outcomes of the projected algorithm of the test system are compared with those obtained by using other conventional power tracing methods. Also, the execution time for different bus systems using the proposed methodology is observed to be comparatively less than other existing approaches, which justifies the fastness and robustness of the presented one.
Effect of Individualized Combined Exercise Versus Group-Based Maintenance Exercise in Patients With Heart Disease and Reduced Exercise Capacity
Authors: Christle Jeffrey W. , Schlumberger Anna , Zelger Otto , Haller Bernhard , Beckers Paul , Myers Jon , Halle Martin , Pressler Axel
Published: December 2017

Purpose:

To compare individualized endurance + resistance exercises (ICE) with a traditional cardiac maintenance program (CMP) on exercise performance in patients with cardiac disease and low exercise capacity.

Methods:

Patients eligible for cardiac rehabilitation with peak exercise capacity <6 metabolic equivalents (METs) were randomly allocated to once-weekly ICE or CMP for 6 mo. ICE used 60 min of individualized moderate endurance and strength exercises. CMP used 60 min of group calisthenics plus relaxation and flexibility exercises. Maximal and submaximal endurance and strength exercise performance were assessed at baseline and 6 mo.

Results:

Seventy patients (70 ± 9 y; 38% female) were included in the intention-to-treat analyses. Large and significant improvements in both submaximal endurance and maximal strength were observed in the ICE group compared with the CMP group. Submaximal exercise duration (+111 ± 112 sec vs +14 ± 120 sec, P < .01), workload (+16 ± 16 W vs +2 ± 17 W, P < .01), and muscular strength (+7 ± 8 kg vs 0 ± 7 kg and +16 ± 14 kg vs 0.2 ± 12 kg for upper- and lower-body strength, P < .01) all favored ICE over CMP. No significant between-group differences were observed in peak exercise performance (+0.05 ± 0.17 W/kg vs +0.04 ± 0.17 W/kg, P = .83) or peak oxygen uptake (−0.1 ± 3.1 mL/kg/min vs +0.6 ± 3.2 mL/kg/min, P = .38).

Conclusions:

Patients with cardiac disease and low exercise capacity improved submaximal exercise performance and muscular strength with once-weekly ICE but not with CMP. Neither ICE nor CMP led to an improvement in peak exercise endurance performance. The implementation of ICE in this population would be feasible and may result in greater benefit for performing activities of daily living.
New developments in understanding focal cortical malformations
Authors: Becker Albert J. , Beck Heinz
Published: December 2017

Purpose of review

Focal cortical dysplasias (FCDs) represent common cortical malformations that are frequently associated with epilepsy. They have so far not been well understood in terms of their molecular pathogenesis, and with respect to mechanisms of seizure emergence.

Recent findings

Several recent studies have succeeded in making significant advances in understanding the molecular genetics, in particular FCD type II. A second major advance has been the development of novel rodent models of FCDs that replicate a somatic mutation seen in humans, lead to a focal lesion, and recapitulate many phenotypic features of human FCDs. We will discuss these recent advances.

These advances promise significant advances in understanding the heterogeneity of FCDs at the molecular genetic level. They also promise a much better understanding of cell-intrinsic and network mechanisms underlying increased seizure susceptibility and altered cognition. Systematic studies utilizing the approaches summarized here promise to lead to specific strategies regarding when and how to treat specific subgroups of FCDs.
Small-scale field testing of Alpha-cypermethrin water-dispersible granules in comparison with the recommended wettable powder formulation for indoor residual spraying against malaria vectors in Benin
Authors: Moiroux Nicolas , Djenontin Armel , Zogo Barnabas , Bouraima Aziz , Sidick Ibrahim , Pigeon Olivier , Pennetier Cédric
Published: December 2017

Backgroud

Pyrethroids are the most common class of insecticide used worldwide for indoor residual spraying (IRS) against malaria vectors. Water-dispersible granules (WG) are a pyrethroid formulation to be applied after disintegration and dispersion in water with less risks of inhalation than using the usual wettable powder (WP) formulation. The objective of this small-scale field study was to evaluate efficacy and duration of insecticidal action of a new alpha-cypermethrin WG (250g a.i./Kg) against susceptible Anopheles gambiae in comparison with the WHO reference product (alpha-cypermethrin WP, 50g a.i./Kg) on the most common indoor surfaces in Benin.

Methods

Both formulations were applied at two target-dose concentrations in houses made of mud and cement in the Tokoli village in southern Benin. We measured the applied dose of insecticide by chemical analysis of filter paper samples collected from the sprayed inner walls. We recorded An. gambiae mortality and knock-down rates every 15 days during 6 months using standard WHO bioassays.

Results

The alpha-cypermethrin WG formulation did not last as long as the WP formulation on both surfaces. The difference is higher with the 30mg/m2 concentration for which the WP formulation reached the 80% mortality threshold during 2 months on the mud-plastered walls (3 months on cement) whereas the WG formulation last only one month (2 months on cement).

Conclusions

The new WG formulation has a shorter efficacy than the WHO recommended WP formulation. In this trial, both the WG and WP formulations had low durations of efficacy that would need at least two rounds of spray to cover the entire transmission season.
Impact of antimicrobial treatment for acute otitis media on carriage dynamics of penicillin-susceptible and penicillin–non-susceptible Streptococcus pneumoniae: secondary analysis of a randomized, double-blind, placebo-controlled trial
Authors: Lewnard Joseph A. , Tähtinen Paula A. , Laine Miia K. , Lindholm Laura , Jalava Jari , Huovinen Pentti , Lipsitch Marc , Ruohola Aino
Published: December 2017

Background

Concerns that antimicrobial treatment may foster selection and transmission of resistant bacterial lineages have led to conflicting guidelines for clinical management of common non-severe infections. However, the impact of antimicrobial treatment on colonization dynamics is poorly understood. We used data from a previously-conducted trial of amoxicillin-clavulanate therapy for acute otitis media (AOM) to understand how antimicrobial treatment impacts the acquisition and clearance of Streptococcus pneumoniae lineages with varying susceptibility to penicillin.

Methods and findings

We measured impacts of antimicrobial treatment on nasopharyngeal carriage of penicillin-susceptible S. pneumoniae (PSSP) and penicillin–non-susceptible S. pneumoniae (PNSP) lineages at end-of-treatment and 15d, 30d, and 60d after treatment in a previously-conducted randomized, double-blind, placebo-controlled trial. Analyses were not specified in the original protocol. Among children 6-35 months of age with stringently-defined AOM, 162 were assigned amoxicillin-clavulanate, and 160 were assigned placebo. Children who did not show clinical improvement received open-label antimicrobial rescue treatment with amoxicillin-clavulanate irrespective of the randomized treatment assignment, to which both patients and physicians were blinded. The intention-to-treat populations of the intervention and placebo arms thus received care resembling immediate antimicrobial therapy and watchful waiting, respectively. Immediate amoxicillin-clavulanate reduced PSSP carriage prevalence by 88% (95%CI: 76-96%) at end-of-treatment and by 27% (–3-49%) after 60d, but did not measurably alter PNSP carriage prevalence throughout follow-up. By end-of-treatment, 7% of children who carried PSSP at enrollment remained colonized in the amoxicillin-clavulanate arm, compared to 61% of PSSP carriers who received placebo; differences in carriage prevalence persisted at least 60d after treatment among children who carried PSSP at enrollment. Among children not carrying pneumococci at enrollment, amoxicillin-clavulanate reduced PSSP acquisition by >80% over 15d. Among children who carried PNSP at enrollment, no differences in carriage prevalence of S. pneumoniae, PSSP, or PNSP were detected at follow-up visits.

Conclusions

In a setting with low PNSP prevalence, antimicrobial therapy for AOM conferred a selective impact on colonizing S. pneumoniae by accelerating clearance, and delaying acquisition, of penicillin-susceptible lineages. Absolute risk of carrying PNSP was unaffected by treatment (ClinicalTrials.gov: NCT00299455; Funding: NIH/NIGMS).
Milieu-Initiated Inversion of the Aqueous Polyproline II/Beta Propensity in the Alanine Tripeptide: Energetics Origin of the Onset of Amyloid Formation
Authors: Mirkin Noemi G. , Krimm Samuel
Published: December 2017

Extending our earlier analogous study of the alanine dipeptide (ADP), we have now analyzed the effect of the external environment on the polyproline II (P) and β relative energies, the P/β propensity, of the alanine tripeptide (ATP). Ab initio calculations of ATP(H2O)19 and ATP(H2O)19(HCl) exhibit the same propensity inversion as in ADP: in the pure-water case the PP conformation is favored while the addition of the HCl molecule results in the ββ conformation being of lower energy. A comparison, following an intermediate insertion and departure of an HCl molecule, shows that the energy of a hydrogen-bonded (H2O)19βATP::βATP(H2O)19 structure is lower than that of the sum of two separate PP systems, i.e., that the aggregated state of the peptide is favored. This arises from the basic physical response to their total environmental influences. Questions about quantitative results from molecular dynamics simulations, obviously needed to analyze longer chains and other side chains, are addressed via rigid-water calculations. The desirability of basing studies of amyloid formation on our proposed alternative milieufolding paradigm is discussed.
Tandem Duplicate Genes in Maize are Abundant and Date to Two Distinct Periods of Time
Authors: Kono Thomas J. Y. , Brohammer Alex B. , McGaugh Suzanne E. , Hirsch Candice N.
Published: December 2017

Tandem duplicate genes are proximally duplicated and as such occur in the same genomic neighborhood. Using the maize B73 and PH207de novogenome assemblies, we identified thousands of tandem gene duplicates that account for ~10% of the genes. These tandem duplicates have a bimodal distribution of estimated ages corresponding to known periods of genomic instability. Tandem duplicates had a number of associated features that suggest origins in nonhomologous recombination based on smaller size distribution and higher rate of containing LTRs than non-tandem duplicates. Within relatively recent tandem duplicate genes, ~26% appear to be undergoing degeneration or divergence in function from the ancestral copy. Our results show that tandem duplicates are abundant in maize, arose in bursts throughout maize evolutionary history under multiple potential mechanisms, and may provide a substrate for novel phenotypic variation.
Transcriptional evaluation of the developmental accuracy, reproducibility and robustness of kidney organoids derived from human pluripotent stem cells
Authors: Phipson Belinda , Er Pei X , Hale Lorna , Yen David , Lawlor Kynan , Takasato Minoru , Sun Jane , Wolvetang Ernst , Oshlack Alicia , Little Melissa H
Published: December 2017

We have previously reported a protocol for the directed differentiation of human induced pluripotent stem cells to kidney organoids comprised of nephrons, proximal and distal epithelium, vasculature and surrounding interstitial elements. The utility of this protocol for applications such as disease modelling will rely implicitly on the developmental accuracy of the model, technical robustness of the protocol and transferability between iPSC lines. Here we report extensive transcriptional analyses of the sources of variation across the timecourse of differentiation from pluripotency to complete kidney organoid, focussing on repeated differentiations to day 18 organoid. Individual organoids generated within the same differentiation experiment show Spearman’s correlation coefficients of >0.99. The greatest source of variation was seen between experimental batch, with the enrichment for genes that also varied temporally between day 10 and day 25 organoids implicating nephron maturation as contributing to transcriptional variance between individual differentiation experiments. A morphological analysis revealed a transition from renal vesicle to capillary loop stage nephrons across the same time period. Distinct iPSC clones were also shown to display congruent transcriptional programs with inter-experimental and inter-clonal variation most strongly associated with nephron patterning. Even epithelial cells isolated from organoids showed transcriptional alignment with total organoids of the same day of differentiation. This data provides a framework for managing experimental variation, thereby increasing the utility of this approach for personalised medicine and functional genomics.
CosMIC: A Consistent Metric for Spike Inference from Calcium Imaging
Authors: Reynolds Stephanie , Abrahamsson Therese , Sjöström P. Jesper , Schultz Simon R. , Luigi Dragotti Pier
Published: December 2017

In recent years, the development of algorithms to detect neuronal spiking activity from two-photon calcium imaging data has received much attention. Meanwhile, few researchers have examined the metrics used to assess the similarity of detected spike trains with the ground truth. We highlight the limitations of the two most commonly used metrics, the spike train correlation and success rate, and propose an alternative, which we refer to as CosMIC. Rather than operating on the true and estimated spike trains directly, the proposed metric assesses the similarity of the pulse trains obtained from convolution of the spike trains with a smoothing pulse. The pulse width, which is derived from the statistics of the imaging data, reflects the temporal tolerance of the metric. The final metric score is the size of the commonalities of the pulse trains as a fraction of their average size. Viewed through the lens of set theory, CosMIC resembles a continuous Sørensen-Dice coefficient — an index commonly used to assess the similarity of discrete, presence/absence data. We demonstrate the ability of the proposed metric to discriminate the precision and recall of spike train estimates. Unlike the spike train correlation, which appears to reward overestimation, the proposed metric score is maximised when the correct number of spikes have been detected. Furthermore, we show that CosMIC is more sensitive to the temporal precision of estimates than the success rate.
Pan-cancer characterisation of microRNA with hallmarks of cancer reveals role of microRNA-mediated downregulation of tumour suppressor genes
Authors: Dhawan Andrew , Scott Jacob G. , Harris Adrian L. , Buffa Francesca M.
Published: December 2017

microRNA are key regulators of the human transcriptome across a number of diverse biological processes, such as development, aging, and cancer, where particular miRNA have been identified as tumour suppressive and oncogenic. In this work, we sought to elucidate, in a comprehensive manner, across 15 epithelial cancer types comprising 7,316 clinical samples from the Cancer Genome Atlas, the association of miRNA expression and target regulation with the pheno-typic hallmarks of cancer. Utilising penalized regression techniques to integrate transcriptomic, methylation and mutation data, we find evidence for a complex map of interactions underlying the relationship of miRNA regulation and the hallmarks of cancer. This highlighted high redundancy for the oncomiR-1 cluster of oncogenic miRNAs, in particular hsa-miR-17-5p. In addition, we reveal extensive miRNA regulation of tumour suppressor genes such as PTEN, FAT4, and CDK12, uncovering an alternative mechanism of repression in the absence of mutation, methylation or copy number changes.
Protein Interaction Screen on Peptide Matrix (PRISMA) reveals interaction footprints and the PTM-dependent interactome of intrinsically disordered C/EBPβ
Authors: Dittmar Gunnar , Perez Hernandez Daniel , Kowenz-Leutz Elisabeth , Kirchner Marieluise , Kahlert Günther , Wesolowski Radoslaw , Baum Katharina , Knoblich Maria , Muller Arnaud , Wolf Jana , Reimer Ulf , Leutz Achim
Published: December 2017

CCAAT enhancer binding protein beta (C/EBPβ) is a pioneer transcription factor that specifies cell differentiation. C/EBPβ is intrinsically unstructured, a molecular feature common to many proteins involved in signal processing and epigenetics. The structure of C/EBPβ differs depending on alternative translation start site usage and multiple post-translational modifications (PTM). Mutation of distinct PTM sites in C/EBPβ alters designated protein interactions and cell differentiation, suggesting a C/EBPβ PTM indexing code determines epigenetic outcomes. Herein, we systematically explored the interactome of C/EBPβ using an array of spot-synthesised C/EBPβ-derived linear tiling peptides with and without PTM, combined with mass spectrometric proteomic analysis of protein interactions. We identified interaction footprints of ~1300 proteins in nuclear cell extracts, many with chromatin modifying, remodelling and RNA processing functions. The results suggest C/EBPβ acts as a multi-tasking molecular switchboard, integrating signal-dependent modifications and structural plasticity to orchestrate interactions with numerous protein complexes directing cell fate and function.

Highlights

Peptide array based interaction proteomics map SLiM and PTM dependent C/EBPβ interactome

Novel links between C/EBPβ, RNA processing, transcription elongation, MLL, NuRD were revealed

C/EBPβ structure organizes modular hub function for gene regulatory machinery

PRISMA is suitable to resolve protein interactions and networks based on intrinsically disordered proteins
Hybrid correction of highly noisy Oxford Nanopore long reads using a variable-order de Bruijn graph
Authors: Morisse Pierre , Lecroq Thierry , Lefebvre Arnaud
Published: December 2017

Motivation

The recent rise of long read sequencing technologies such as Pacific Biosciences and Oxford Nanopore allows to solve assembly problems for larger and more complex genomes than what allowed short reads technologies. However, these long reads are very noisy, reaching an error rate of around 10 to 15% for Pacific Biosciences, and up to 30% for Oxford Nanopore. The error correction problem has been tackled by either self-correcting the long reads, or using complementary short reads in a hybrid approach, but most methods only focus on Pacific Biosciences data, and do not apply to Oxford Nanopore reads. Moreover, even though recent chemistries from Oxford Nanopore promise to lower the error rate below 15%, it is still higher in practice, and correcting such noisy long reads remains an issue.

Results

We present HG-CoLoR, a hybrid error correction method that focuses on a seed-and-extend approach based on the alignment of the short reads to the long reads, followed by the traversal of a variable-order de Bruijn graph, built from the short reads. Our experiments show that HG-CoLoR manages to efficiently correct Oxford Nanopore long reads that display an error rate as high as 44%. When compared to other state-of-the-art long read error correction methods able to deal with Oxford Nanopore data, our experiments also show that HG-CoLoR provides the best trade-off between runtime and quality of the results, and is the only method able to efficiently scale to eukaryotic genomes.

Availability and implementation

HG-CoLoR is implemented is C++, supported on Linux platforms and freely available athttps://github.com/morispi/HG-CoLoR

Contact:pierre.morisse2@univ-rouen.fr

Supplementary information

Supplementary data are available atBioinformaticsonline.
Increased susceptibility to intracellular bacteria and necrotic inflammation driven by a dysregulated macrophage response to TNF
Authors: Bhattacharya Bidisha , Chattrerjee Sujoy , Berland Robert , Pichugin Alexander , Gao Yuanwei , Connor John , Ivanov Alexander , Yan Bo-Shiun , Kobzik Lester , Kramnik Igor
Published: December 2017

Host susceptibility to tuberculosis and several other intracellular bacteria is controlled by a mouse genetic locus, sst1. Necrotic inflammatory lesions, similar to human TB granulomas, are a hallmark of the sst1 susceptible phenotype. Our previous work established that increased disease severity in sst1 susceptible mice reflects dysfunctional macrophage effector or tolerance mechanisms, but the molecular mechanisms have been unclear.

We demonstrate that sst1-deficient macrophages develop aberrant, biphasic responses to TNF, characterized by super-induction of stress and type I interferon pathways after prolonged TNF stimulation. This late stage response was initiated by oxidative stress and Myc. It was driven via a JNK - IFNβ - PKR feed-forward circuit locking the susceptible macrophages in a state of escalating stress. Consequently, prolonged TNF stimulation of the susceptible macrophages reduced their resilience to subsequent infection with intracellular bacteria.

The data support a generalizable paradigm in host - pathogen interactions, where susceptibility emerges gradually within inflammatory tissue due to imbalanced macrophage responses to growth, differentiation, activation and stress stimuli prior to encountering pathogens. This explains how successful pathogens may locally bypass mechanisms of resistance in otherwise immunocompetent hosts and suggests novel therapeutic strategies.
Multiplexed imaging of high density libraries of RNAs with MERFISH and expansion microscopy
Authors: Wang Guiping , Moffitt Jeffrey R. , Zhuang Xiaowei
Published: December 2017

As an image-based single-cell transcriptomics approach, multiplexed error-robust fluorescence in situ hybridization (MERFISH) allows hundreds to thousands of RNA species to be identified, counted and localized in individual cells while preserving the native spatial context of RNAs. In MERFISH, RNAs are identified via a combinatorial labeling approach that encodes RNA species with error-robust barcodes followed by sequential rounds of single-molecule FISH (smFISH) to read out these barcodes. The accuracy of RNA identification relies on spatially separated signals from individual RNA molecules, which limits the density of RNAs that can be measured and makes the multiplexed imaging of a large number of high-abundance RNAs challenging. Here we report an approach that combines MERFISH and expansion microscopy to substantially increase the total density of RNAs that can be measured. Using this approach, we demonstrate accurate identification and counting of RNAs, with a near 100% detection efficiency, in a ~130-RNA library composed of many high-abundance RNAs, the total density of which is more than 10 fold higher than previously reported. In parallel, we demonstrate the combination of MERFISH with immunofluorescence. These advances increase the versatility of MERFISH and will facilitate its application of a wide range of biological problems.
Wolbachia Infection Associated with Increased Recombination in Drosophila
Authors: Singh Nadia D.
Published: December 2017

Wolbachia is maternally-transmitted endosymbiotic bacteria that infects a large diversity of arthropod and nematode hosts. Some strains of Wolbachia are parasitic, manipulating host reproduction to benefit themselves, while other strains of Wolbachia exhibit obligate or facultative mutualisms with their host. The effects of Wolbachia on its host are many, though primarily relate to host immune and reproductive function. Here we test the hypothesis that Wolbachia infection alters the frequency of homologous recombination during meiosis. We useD. melanogasteras a model system, and survey recombination in eight Wolbachia-infected and Wolbachia-uninfected strains, controlling for genotype. We measure recombination in two intervals of the genome. Our results indicate that Wolbachia infection is associated with increased recombination in one genomic interval and not the other. The effect of Wolbachia infection on recombination is thus heterogenous across the genome. Our data also indicate a reproductive benefit of Wolbachia infection; infected females show higher fecundity than their uninfected genotypic controls. Given the prevalence of Wolbachia infection in natural populations, our findings suggest that Wolbachia infection is likely to contribute to recombination rate and fecundity variation among individuals in nature.
Cervical spine traumatic epidural haematomas: Incidence and characteristics
Authors: Brichko Lisa , Giddey Birinder , Tee Jin , Niggemeyer Louise , Fitzgerald Mark
Published: December 2017

Objective

Cervical spine traumatic epidural haematomas (CSTEH) can cause potentially devastating neurological deficits if not promptly identified. Study aims were to determine the incidence, characteristics and outcomes for patients with CSTEH.

Methods

A retrospective study was performed at a tertiary hospital with an adult Level 1 Trauma Centre on all consecutive patients diagnosed with CSTEH over a 4 year period. Medical record review was undertaken for all patients with the diagnoses of CSTEH to identify patient characteristics including age, mechanism of injury and co‐morbid conditions. Additional data was extracted regarding radiology interpretation, surgical interventions, thromboembolic chemoprophylaxis use, discharge disposition and neurological outcomes.

Results

A total of 27 888 patients were admitted with traumatic injuries between 1 July 2010 and 30 June 2014, of which 1916 patients sustained cervical spine injuries. The incidence of CSTEH was 0.6% among all trauma patients and 9.1% among patients with any cervical spine injury. Of those with CSTEH, 89 patients (50.9%) had neurological deficits consistent with the anatomical location of the epidural haematoma. Magnetic resonance imaging diagnosed CSTEH in 132 patients (75.4%), of whom 23 patients (13.1%) had normal computed tomography cervical spine imaging. Among the patients diagnosed with CSTEH, 13 (7.4%) died and 78 (44.6%) required cervical spine surgical decompressions.

Conclusion

This study shows a high incidence of CSTEH among trauma patients. CSTEH is associated with significant morbidity and mortality. High clinical vigilance is required to allow the request and acquisition of urgent magnetic resonance imaging to diagnose CSTEH as the entity is often not evident on initial cervical spine computed tomography investigations.
Mechanism of Antibacterial Activities of a Rice Hull Smoke Extract (RHSE) Against Multidrug‐Resistant Salmonella Typhimurium In Vitro and in Mice
Authors: Kim Sung Phil , Lee Sang Jong , Nam Seok Hyun , Friedman Mendel
Published: December 2017

The present study tested antibacterial activity of a rice hull smoke extract (RHSE) against a multidrug‐resistant strain of Salmonella Typhimurium and examined its mode of suppressive action in vitro and in mice. In vitro studies showed that the minimum inhibitory concentration (MIC) value of RHSE was 1.29% (v/v). The inactivation was confirmed by complete loss of cell viability in the range of 104 to 107 colony forming units of the resistant Salmonella Typhimurium strain. Agarose and sodium dodecyl sulfate–polyacrylamide gel electrophoreses were used to evaluate the integrities of bacterial genomic DNA and total cellular protein profiles. The antibacterial action of RHSE results from a leakage of intracellular macromolecules following rupture of bacterial cells. Scanning electron microscopy of the cells shows that RHSE also induced deleterious morphological changes in the bacterial cell membrane of the pathogens. In vivo antibacterial activity of RHSE at a 1 × MIC concentration was examined in a bacterial gastroenteritis model using Balb/c mice orally infected with the Salmonella Typhimurium. The results show greatly decreased excretion of the bacteria into the feces and suppressed translocation of the bacteria to internal organs (cecum, mesenteric lymph node, spleen, and liver) compared with the infected mice not subjected to the RHSE treatment. Collectively, the present findings indicate that the mechanism of the antibacterial activities both in vitro and in the gastroenteritis environment of the animal model is the result of the direct disruption of cell structure, leading to cell death. RHSE has the potential to serve as a multifunctional food additive that might protect consumers against infections by antibiotic‐resistant microorganisms.

Practical Application

The rice hull derived liquid smoke has the potential to complement widely used wood‐derived smoke as an antimicrobial flavor and health‐promoting formulation for application in foods and feeds.
Validation of screening questionnaires for evaluation of knee osteoarthritis prevalence in the general population of Singapore
Authors: Leung Ying‐Ying , Ma Stefan , Noviani Maria , Wong Steven B.‐S. , Lee Chee Min , Soh Irene A.‐L. , Thumboo Julian
Published: December 2017

Background

The prevalence of symptomatic knee osteoarthritis (KOA) in Singapore is unknown. We aimed to: (i) validate questionnaires to screen for symptomatic KOA; and (ii) estimate the prevalence of symptomatic KOA in Singapore using the validated algorithms.

Methods

Subjects aged ≥50 years were evaluated for symptomatic KOA based on American College of Rheumatology clinical and radiographic criteria in a rheumatology clinic, and completed three sets of adapted screening questionnaires. The better performing screening questionnaire with adequate sensitivity and specificity was adminitered to a nationally representative sample of survey subjects (n = 3364) to estimate the weighted prevalence of symptomatic KOA in Singapore.

Results

Out of 146 subjects evaluated in the clinic, 45 had symptomatic KOA. A screening algorithm which consisted of three KOA symptoms or one symptom plus physician‐diagnosed KOA produced high specificity (0.95, 95% confidence intervals [CI]: 0.88–0.98) but low sensivity (0.44, 95% CI: 0.30–0.60). Replacing the term ‘KOA’ with ‘physician‐diagnosed ageing‐related knee problem’ improved the sensivity (0.62, 95% CI: 0.47–0.76) without significantly compromising the specificity (0.87, 95% CI: 0.79–0.93). The prevalence of symptomatic KOA weighted to the Singapore population distribution were 4.7% and 11%, using the most conservative and more liberal algorithms, respectively. There was a sharp rise in prevalence after age of 40. The weighted prevalence of KOA was higher in women and among Indian and Malay than Chinese.

Conclusion

Our study adapted and validated questionnaires to the local context to screen for symptomatic KOA. We estimated the prevalence of symptomatic KOA in Singapore utilizing the better‐performing algorithms.
Drivers of tight carbon control in the context of climate change regulation
Authors: Bui Binh , Chapple Larelle , Truong Thu Phuong
Published: December 2017

Our study examines the drivers of tight budgetary control in carbon management in the context of climate change regulation. Using the setting of New Zealand Emissions Trading Scheme (ETS), our study explores how firms manage their carbon performance using carbon‐focused budgetary control. Based on a survey data from New Zealand firms, including both those with and those without an ETS compliance obligations, our results suggest that economic and regulatory environmental pressures, the level of proactiveness of emissions management strategy, the level of integration of carbon issues in strategic and operational processes and the perceived importance of carbon issues are the significant drivers of tight carbon‐focused budgetary control.
Coping of parents and siblings with the death of a child with cancer: death after terminal care compared with death during active anticancer therapy
Authors: Sirkiä K , Saarinen-Pihkala UM , Hovi L
Published: December 2017

Sirkiä K, Saarinen‐Pihkala UM, Hovi L. Coping of parents and siblings with the death of a child with cancer: death after terminal care compared with death during active anticancer therapy: Acta Pædiatr 2000; 89: 717–21. Stockholm. ISSN 0803‐5253

Seventy pediatric patients with cancer treated at the Hospital for Children and Adolescents, University of Helsinki, Finland, died while in terminal care and 30 children of therapy‐related complications during active anticancer therapy in the period 1987–92. The purpose of this study was to compare these groups and characterize the main problems of the families during the mourning process. The method of evaluation was a structured interview of every parent separately. Parents of 60/70 children after terminal care, and parents of 26/30 children who died during active anticancer therapy, were interviewed. Unexpectedly, differences were minimal between families who lost a child after terminal care and those whose child died during active anticancer therapy. Parents reported physical and/or mental problems with similar frequency (39% and 34%); average self‐reported recovery times were similar (14 and 16 mo); return to work was similar in both groups, 70% returning doing so within 1 mo. However, pronounced differences were observed between the mothers and the fathers; the mothers requiring longer recovery times and returning to work later. Of the siblings, 18% in the terminal care group had problems compared with 32% in the active therapy group. These included fear, behavioral problems, problems with friends and school‐related problems.

In conclusion, when a child with cancer dies, the ability of the respective families to cope does not seem to differ whether the child dies after terminal care or during active anticancer therapy. The inevitable loss of the child is the major event. Most parents and siblings have the potential and ability to recover normally after the death of a child, although they will never be completely the same.
Contributions to Canadian economic history: The last 30 years
Authors: Hamilton Gillian C. , Keay Ian , Lewis Frank D.
Published: December 2017

The cliometric revolution that transformed economic history in the US in the 1960s was soon embraced by Canadian economic historians. Many of the important issues surrounding Canadian development remained the same: the role of resources, the place of international trade, immigration, capital accumulation and interactions with Native Americans, among others. But beginning in the 1960s, and certainly over the last 30 years, economic historians of Canada have addressed them with the tools of modern economics, both theoretical and empirical. We highlight the recent work emphasizing not just the methods but also the fundamental ways our understanding of Canadian history has been changed.
Long noncoding RNA LINC00978 promotes cancer growth and acts as a diagnostic biomarker in gastric cancer
Authors: Fu Min , Huang Zhenhua , Zang Xueyan , Pan Lei , Liang Wei , Chen Jingyan , Qian Hui , Xu Wenrong , Jiang Pengcheng , Zhang Xu
Published: December 2017

Objectives

Long noncoding RNAs (lncRNAs) play important roles in cancer development and progression. The deregulated expression of LINC00978 has been reported in human cancers. However, the expression pattern and biological roles of LINC00978 in gastric cancer (GC) remain unclear. In this study, we investigated the potential roles and clinical value of LINC00978 in gastric cancer.

Materials and methods

QRT‐PCR was performed to investigate the expression of LINC00978 in gastric cancer cell lines, tissues and serum samples. Cell counting, colony formation, transwell migration and matrigel invasion assays were performed to determine the effects of shRNA‐mediated knockdown of LINC00978 on gastric cancer cell functions. In vivo tumour growth assay was also conducted. Flow cytometry, immunohistochemistry, western blot and qRT‐PCR were used for potential mechanism study.

Results

LINC00978 expression level was elevated in GC tumour tissues, serum samples and cell lines. The expression level of LINC00978 was significantly correlated with tumour size (P = 0.02), lymphatic metastasis (P = 0.009) and TNM stage (P = 0.009). LINC00978 knockdown inhibited the proliferation of GC cells by suppressing cell cycle progression and inducing apoptosis. LINC00978 knockdown also inhibited the migration and invasion of GC cells. In addition, LINC00978 knockdown inhibited the activation of TGF‐β/SMAD signalling pathway and the process of epithelial‐mesenchymal transition (EMT) in GC cells. Moreover, the in vivo tumorigenicity of LINC00978 knockdown GC cells in mice was significantly decreased.

Conclusions

LINC00978 promotes gastric cancer progression and may serve as a potential biomarker for GC.
Should Congestion Tolls be Set by the Government or by the Private Sector? The Knight–Pigou Debate Revisited
Authors: Salant Stephen , Seegert Nathan
Published: December 2017

This paper clarifies issues debated by A. C. Pigou and Frank Knight about correcting inefficient use of congestible resources, focusing for concreteness on their original example of road congestion. Instead of government‐imposed Pigouvian access fees, Knight favoured access fees set by private toll‐setters. We consider the case of n≥2 congestible roads and an uncongestible road of arbitrary speed. Knight argued that in the case of a single congestible road, a private toll‐setter would always choose the toll that Pigou recommended, hence the allocation would minimize aggregate commute time without government meddling. We find instead that two or more toll‐setters would never choose Pigouvian tolls except in the special case of a sufficiently fast uncongestible road. Moreover, for uncongestible roads of slower speed, the allocation of motorists under Knight's proposal is almost never efficient. Whenever it is inefficient, motorists are strictly worse off when they pay tolls set by private firms instead of paying government‐imposed tolls, and aggregate toll revenue is also lower. Nevertheless, if the private sector does set tolls, then the full cost to motorists can be limited if the government provides an uncongestible alternative, such as a train, to offer potential competition along the same route.
Quantifying River‐Groundwater Interactions of New Zealand's Gravel‐Bed Rivers: The Wairau Plain
Authors: Wöhling Thomas , Gosses Moritz J. , Wilson Scott R. , Davidson Peter
Published: December 2017

New Zealand's gravel‐bed rivers have deposited coarse, highly conductive gravel aquifers that are predominantly fed by river water. Managing their groundwater resources is challenging because the recharge mechanisms in these rivers are poorly understood and recharge rates are difficult to predict, particularly under a more variable future climate. To understand the river‐groundwater exchange processes in gravel‐bed rivers, we investigate the Wairau Plain Aquifer using a three‐dimensional groundwater flow model which was calibrated using targeted field observations, “soft” information from experts of the local water authority, parameter regularization techniques, and the model‐independent parameter estimation software PEST. The uncertainty of simulated river‐aquifer exchange flows, groundwater heads, spring flows, and mean transit times were evaluated using Null‐space Monte‐Carlo methods. Our analysis suggests that the river is hydraulically perched (losing) above the regional water table in its upper reaches and is gaining downstream where marine sediments overlay unconfined gravels. River recharge rates are on average 7.3 m3/s, but are highly dynamic in time and variable in space. Although the river discharge regularly hits 1000 m3/s, the net exchange flow rarely exceeds 12 m3/s and seems to be limited by the physical constraints of unit‐gradient flux under disconnected rivers. An important finding for the management of the aquifer is that changes in aquifer storage are mainly affected by the frequency and duration of low‐flow periods in the river. We hypothesize that the new insights into the river‐groundwater exchange mechanisms of the presented case study are transferable to other rivers with similar characteristics.
Social service systems for vulnerable children and families in low‐ and middle‐income countries: Establishing definitions and key components
Authors: Crea Thomas M. , Reynolds Andrew D. , Bunkers Kelley McCreery , Bishop Caroline M.
Published: December 2017

Systems strengthening in low‐ and middle‐income countries has long been a topic of concern in global health. By comparison, until very recently, little attention has been paid to the importance of strengthening social service systems to provide a holistic perspective of children's and families' multifaceted strengths and vulnerabilities. This study has reviewed existing literature on the definitions and components of social service systems and provides an analysis of data from key informants in the field of global social welfare. Based on this information, a set of key components is presented and compared, derived from the literature and expert interviews. Existing challenges for the field include establishing consensus on terminology and critical components, implementing and documenting critical components, and linking these components to client outcomes.
Social protection and persons with disabilities
Authors: Devandas Aguilar Catalina
Published: December 2017

Social protection is an essential condition for social and economic development for all, but particularly for those who experience poverty and social exclusion. Social protection programmes can play a crucial role in alleviating and preventing poverty and vulnerability to secure people's well‐being. They can also enhance the productivity, employability and economic development of people by creating better income‐earning opportunities for them. Moreover, social protection can foster social inclusion and participation by ensuring effective access to food, health care, education and support services. Thus, well‐designed social protection programmes have the potential to directly improve the enjoyment of rights of persons with disabilities. Regrettably, traditional disability‐welfare approaches have promoted the opposite, building and spreading charity and medical perspectives in social protection responses. As a result, for too long, many national social protection systems resulted in furthering paternalism, dependence, segregation and institutionalization of persons with disabilities, limiting their opportunities to live independently in their communities. The United Nations (UN) Convention on the Rights of Persons with Disabilities challenges these views, promoting social protection systems that are inclusive of persons with disabilities and which facilitate active citizenship, social inclusion and community participation. The Convention calls on States parties to ensure that persons with disabilities receive equal access to mainstream social protection programmes and services as well as access to specific programmes and services for disability‐related needs and expenses such as support services. Against this background, this article aims to discuss why and how States and other stakeholders should ensure the establishment of disability‐inclusive social protection systems, in conformity with the UN Convention on the Rights of Persons with Disabilities.
The politics of rights‐based, transformative social policy in South and Southeast Asia
Authors: Koehler Gabriele
Published: December 2017

A key normative principle of transformative social policy is that it is rights‐based. This implies that it be universal, as a right extended categorically to all persons in a defined situation, or to all citizens, or, in its most radical form, as applicable to all residents regardless of citizenship status. To be transformative, social policy also needs to tackle the root causes of inequalities and social injustices. In the recent past, approaches emerged in a number of countries in Southeast Asia and South Asia that pointed in the direction of universal, rights‐based social policy. These suggest that a “social turn” took place – a shift to ideas and policies that prioritize social issues. In the cases under review (India, Myanmar, Nepal, Pakistan and Thailand), the trends towards a universal, rights‐based approach to social services and social transfers were in each case politically driven and a result of changes in government – the social turns were the outcome of contestation. At present, these countries are experiencing political backlashes, with democratic processes and civil society under severe attack. This article seeks to make two points. First, a rights‐based, transformative policy approach and a social turn do not come automatically: it is always the result of contestation, be it from the electorate and their interests groups, or from competition between political parties. Second, acquired rights and moves towards transformation can be dismantled. In the current global political rollback, there is a need to defend and fight for transformative and rights‐based social policy.
Experimental candidosis. Pathogenesis, prevention, therapy
Authors: Segal Esther
Published: December 2017

This article highlights some aspects of candidosis which were explored in different models and which yielded relevant information with respect to pathogenesis as well as possibilities of prevention and treatment of candidosis.
Special pharmacokinetics of fluconazole in septic, obese and burn patients
Authors: Pittrow L. , Penk A.
Published: December 2017

Although there are many potential changes of pharmacokinetic parameters in patients with thermal injury, obesity or septicemia, data about the actual effect on pharmacokinetics and clinical efficacy of fluconazole are very limited. As current dosing recommendations are derived from healthy subjects and patients with normal weight, these recommendations may be inaccurate when applied to the patient populations mentioned above. Pharmacokinetic data of 14 patients with thermal injury were reviewed and revealed a shorter half life and more rapid clearance of fluconazole. In a subgroup of five patients, distribution volume was up to 2 times larger as usual with no relationship to creatinine clearance and degree of burns. In one extremely obese patient treated with fluconazole 1200 mg/day*, the corresponding mean steady‐state plasma concentration and AUC were decreased with an increase of fluconazole clearance possibly due to a larger volume of distribution. In patients with septicemia, fluconazole plasma levels appear to be highly variable. As a considerable number of these patients develops acute renal failure, renal replacement therapy may be indicated which may require substantial dosage modifications of fluconazole.