bluuebunny/crossref_metadata_2025 huggingface dataset:
Muscarinic m2 receptor‐mediated actin polymerization via PI3 kinase γ and integrin‐linked kinase in gastric smooth muscle
Authors: Mahavadi Sunila , Grider John R. , Murthy Karnam S.
Published: November 2018

Background

Actin polymerization plays an important role in smooth muscle contraction. Integrin‐linked kinase (ILK) was shown to mediate actin polymerization in airway smooth muscle. The role of ILK in actin polymerization in response to m2 receptor activation was not in gastric smooth muscle.

Methods

Phosphorylation of paxillin, neuronal Wiskott‐Aldrich syndrome protein (N‐WASp), and association of paxillin with GEF proteins (Cool2/αPix [Cool2/PAK‐interacting exchange factor alpha], Cool1/βPix [Cool1/PAK‐interacting exchange factor beta], and DOCK 180 [Dedicator of cytokinesis]) and N‐WASp with Arp2/3 complex were measured by western blot. Activation of Cdc42 was determined using an antibody for activated Cdc42. Actin polymerization was measured as an increase in F‐actin/G‐actin ratio.

Results

Phosphorylation of paxillin, an association of paxillin with GEF proteins, Cdc42 activity, and actin polymerization were increased in response to m2 receptor activation in gastric smooth muscle cells. The increases in paxillin phosphorylation, Cdc42 activity, and actin polymerization were inhibited by a PI3Kγ inhibitor (AS‐605240), ILK siRNA, and ILK dominant negative mutant (ILK [R211]). Increase in actin polymerization was also inhibited by Cdc42 dominant negative mutant (Cdc42 [T17N]). Increases in the association of paxillin with GEF proteins, phosphorylation of N‐WASp and its association with Arp2/3 complex were inhibited by ILK (R211).

Conclusion

In gastric smooth muscle cells, activation of PI3Kγ by muscarinic m2 receptors causes ILK‐dependent phosphorylation of paxillin, an association of paxillin with Cdc42 GEF proteins and activation of Cdc42, which, in turn, causes phosphorylation of N‐WASp and its association with Arp2/3 complex leading to actin polymerization.
The E domain of CRR2 participates in sequence‐specific recognition of RNA in plastids
Authors: Ruwe Hannes , Gutmann Bernard , Schmitz‐Linneweber Christian , Small Ian , Kindgren Peter
Published: November 2018

Pentatricopeptide repeat (PPR) proteins are modular RNA‐binding proteins involved in different aspects of RNA metabolism in organelles. PPR proteins of the PLS subclass often contain C‐terminal domains that are important for their function, but the role of one of these domains, the E domain, is far from resolved. Here, we elucidate the role of the E domain in CRR2 in plastids.

We identified a surprisingly large number of small RNAs that represent in vivo footprints of the Arabidopsis PLS‐class PPR protein CRR2. An unexpectedly strong base conservation was found in the nucleotides aligned to the E domain. We used both in vitro and in vivo experiments to reveal the role of the E domain of CRR2.

The E domain of CRR2 can be predictably altered to prefer different nucleotides in its RNA ligand, and position 5 of the E1‐motif is biologically important for the PPR–RNA interaction. The ‘code’ of the E domain PPR motifs is different from that of P‐ and S‐motifs.

The findings presented here show that the E domain of CRR2 is involved in sequence‐specific interaction with its RNA ligand and have implications for our ability to predict RNA targets for PLS‐PPRs and their use as biotechnological tools to manipulate specific RNAs in vivo.
Quantitative resistance to clubroot infection mediated by transgenerational epigenetic variation in Arabidopsis
Authors: Liégard Benjamin , Baillet Victoire , Etcheverry Mathilde , Joseph Evens , Lariagon Christine , Lemoine Jocelyne , Evrard Aurélie , Colot Vincent , Gravot Antoine , Manzanares‐Dauleux Maria J. , Jubault Mélanie
Published: November 2018

Quantitative disease resistance, often influenced by environmental factors, is thought to be the result of DNA sequence variants segregating at multiple loci. However, heritable differences in DNA methylation, so‐called transgenerational epigenetic variants, also could contribute to quantitative traits. Here, we tested this possibility using the well‐characterized quantitative resistance of Arabidopsis to clubroot, a Brassica major disease caused by Plasmodiophora brassicae.

For that, we used the epigenetic recombinant inbred lines (epiRIL) derived from the cross ddm1‐2 × Col‐0, which show extensive epigenetic variation but limited DNA sequence variation. Quantitative loci under epigenetic control (QTLepi) mapping was carried out on 123 epiRIL infected with P. brassicae and using various disease‐related traits.

EpiRIL displayed a wide range of continuous phenotypic responses. Twenty QTLepi were detected across the five chromosomes, with a bona fide epigenetic origin for 16 of them. The effect of five QTLepi was dependent on temperature conditions. Six QTLepi co‐localized with previously identified clubroot resistance genes and QTL in Arabidopsis.

Co‐localization of clubroot resistance QTLepi with previously detected DNA‐based QTL reveals a complex model in which a combination of allelic and epiallelic variations interacts with the environment to lead to variation in clubroot quantitative resistance.
Uncertainties and limitations of using carbon‐13 and oxygen‐18 leaf isotope exchange to estimate the temperature response of mesophyll CO2 conductance in C3 plants
Authors: Sonawane Balasaheb V. , Cousins Asaph B.
Published: November 2018

The internal CO2 gradient imposed by mesophyll conductance (gm) reduces substrate availability for C3 photosynthesis. With several assumptions, estimates of gm can be made from coupled leaf gas exchange with isoflux analysis of carbon ∆13C‐gm and oxygen in CO2, coupled with transpired water (H2O) ∆18O‐gm to partition gm into its biochemical and anatomical components. However, these assumptions require validation under changing leaf temperatures.

To test these assumptions, we measured and modeled the temperature response (15–40°C) of ∆13C‐gm and ∆18O‐gm along with leaf biochemistry in the C3 grass Panicum bisulcatum, which has naturally low carbonic anhydrase activity.

Our study suggests that assumptions regarding the extent of isotopic equilibrium (θ) between CO2 and H2O at the site of exchange, and that the isotopic composition of the H2O at the sites of evaporation () and at the site of exchange () are similar, may lead to errors in estimating the ∆18O‐gm temperature response. The input parameters for ∆13C‐gm appear to be less sensitive to temperature. However, this needs to be tested in species with diverse carbonic anhydrase activity.

Additional information on the temperature dependency of cytosolic and chloroplastic pH may clarify uncertainties used for ∆18O‐gm under changing leaf temperatures.
Robots and AI at work: the prospects for singularity
Authors: Upchurch Martin
Published: November 2018

This paper seeks to address emerging debates and controversies on the impact of robots and artificial intelligence on the world of work. Longer term discussions of technological ‘singularity’ are considered alongside the socio‐technical and economic constraints on the application of robotics and AI. Evidence of robot ‘take‐up’ is gathered from reports of the International Federation of Robotics and from case vignettes reported elsewhere. In assessing the contemporary relationship between singularity, robotics and AI, the article reflects briefly on the two ‘tests’ of artificial ‘intelligence’ proposed by the pioneer computer scientist Alan Turing, and comments on the efficacy of his ‘tests’ in contemporary applications. The paper continues by examining aspects of public policy and concludes that technological singularity is far from imminent.
Eligibility for subcutaneous implantable cardioverter defibrillators in the adult congenital heart disease population
Authors: Garside Hannah , Leyva Francisco , Hudsmith Lucy , Marshall Howard , de Bono Joseph
Published: November 2018

Background

Patients with adult congenital heart disease (ACHD) have an increased risk of arrhythmic and sudden cardiac death. The subcutaneous implantable cardioverter defibrillator (S‐ICD) provides a potentially safer alternative to transvenous ICDs in ACHD. Suitability for S‐ICD depends on the surface electrocardiogram (ECG), which is often abnormal in ACHD patients. This study investigates the proportion of ACHD patients who meet the screening criteria for S‐ICD implantation.

Methods

A standard screening ECG was performed in 102 patients with complex ACHD (Tetralogy of Fallot, Fontan circulation, and transposition of the great arteries). This process was repeated postexercise for patients who also had an exercise test.

Results

Three quarters (75.4%) of ACHD patients meet screening criteria for an S‐ICD with at least one suitable vector. The most common number of acceptable vectors in the eligible group was two (35% of total population). In only 12% of total population, all three vectors were suitable while only one vector was suitable in 28% of total population. The primary vector (equivalent of ECG lead III) was the most common suitable vector, found in 62% of participants who had appropriate sensing vectors. Twenty‐five (24.5%) patients failed to meet the S‐ICD screening criteria. Of these, 14 had repaired tetralogy of Fallot. A total of 92% of patients with a Fontan circulation met ECG screening criteria. Of those who had the protocol repeated following their cardiopulmonary exercise test (n = 14), only one additional patient failed to meet the eligibility criteria.

Conclusions

A quarter of ACHD patients do not meet the eligibility criteria for the S‐ICD. However, more than 90% of patients with a Fontan circulation are suitable for an S‐ICD.
Healthy hearts in pediatric heart transplant patients with an exercise and diet intervention via live video conferencing—Design and rationale
Authors: Chen Angela C. , Rosenthal David N. , Couch Sarah C. , Berry Samuel , Stauffer Katie J. , Brabender Jerrid , McDonald Nancy , Lee Donna , Barkoff Lynsey , Nourse Susan E. , Kazmucha Jeffrey , Wang C. Jason , Olson Inger , Selamet Tierney Elif Seda
Published: November 2018

Background

Pediatric heart transplant (PedHtx) patients have increased cardiovascular risk profiles that affect their long‐term outcomes and quality of life. We designed a 12‐ to 16‐week diet and exercise intervention delivered via live video conferencing to improve cardiovascular health. Our methodology and baseline assessment of the first 13 enrolled patients are reported.

Methods

Inclusion criteria are as follows: (a) 8‐19 years old; (b) heart transplant >12 months; (c) ability to fast overnight; (d) cardiac clearance by cardiologist; and (e) presence of an adult at home during exercise sessions for patients <14 years old. Exclusion criteria are as follows: (a) acute illness; (b) latex allergy; (c) transplant rejection <3 months ago; and (d) multi‐organ transplantation. The intervention consists of one diet and three exercise sessions weekly via live video conferencing. Study visits are conducted at baseline, intervention completion, and end of maintenance period.

Results

A total of 13 participants (15.2 [2.3] years) have been enrolled. Median percent‐predicted VO2 max was 56.8 [20.7]% (10 patients <70%). Ten patients had abnormal endothelial function (reactive hyperemia index <1.9; 1.4 [0.325]) and 11 patients had stiff arteries (pulse wave velocity ≧5.5 m/s for 15‐19 years, ≧4.5 m/s for 8‐14 years; 5.6 [0.7] m/s). Patients had suboptimal diets (saturated fat: 22.7 [23.8] g/d, sodium: 2771 [1557] mg/d) and were sedentary at a median of 67.5 [13.8]% of their time.

Conclusions

Baseline assessment confirms that PedHtx patients have abnormal cardiac, vascular, and functional health indices, poor dietary habits, and are sedentary. These results support the rationale to test the feasibility and impact of a non‐pharmacologic lifestyle intervention in this patient population.
Prevalence of behavioural and psychological symptoms of dementia in cognitively impaired elderly residents of long‐term care facilities in East Asia: a cross‐sectional study
Authors: Makimoto Kiyoko , Kang Younhee , Kobayashi Sayuri , Liao Xiao‐yan , Panuthai Sirirat , Sung Huei‐chuan , Suzuki Mizue , Terada Saya , Yamakawa Miyae
Published: November 2018

Objective

The aim of this study was to compare the prevalence of behavioural and psychological symptoms of dementia (BPSD) in cognitively impaired elderly residents of long‐term care facilities in East Asia and to explore the factors associated with these patterns.

Methods

This was a cross‐sectional survey of BPSD in cognitively impaired elderly residents of long‐term care facilities in Japan, South Korea, China, Taiwan, and Thailand.

The Mini‐Mental State Examination, Clinical Dementia Rating (CDR), and Neuropsychiatric Inventory, Nursing Home version (NPI‐NH), were used to assess cognitive status, dementia severity, and BPSD, respectively. NPI‐NH subscale severity scores were multiplied by frequency scores to obtain the subscale scores and aggregated into two groups based on score (clinically insignificant = 1– 3; clinically significant ≥4).

Results

Data from 662 people were analyzed. Median age, median Mini‐Mental State Examination scores, and median CDR scores differed significantly among the seven study sites. The prevalence of BPSD varied from 64% in Taiwan to 100% in dementia care units in Japan, and the median total NPI‐NH scores ranged from 2 in Taiwan to 14 in dementia care units in Japan. After stratification of the sample by dementia severity and clinical significance of NPI‐NH scores, differences in the prevalence of clinically significant BPSD were mostly observed among facilities dedicated to dementia patients in the CDR 1 group. In the CDR 3 group, the prevalence of some clinically significant BPSD, such as apathy, was high even among study sites with low median total NPI‐NH scores.

Conclusions

Our findings may suggest referral and selection biases in the study sites. Future prospective studies are needed to address the impact of environmental and care factors on the occurrence of BPSD in Asian countries.
Toddler risk and protective characteristics: Common and unique genetic and environmental influences
Authors: Rea‐Sandin Gianna , Clifford Sierra , Valiente Carlos , Lemery‐Chalfant Kathryn
Published: November 2018

The goal of this study was to disentangle the common and unique genetic and environmental influences on social–emotional competence, problem behavior, physiological dysregulation, and negative emotionality (NE) in toddlers. The sample consisted of 243 twin pairs (mean age =31.94 months) rated by primary caregivers (>95% mothers) on the Children's Behavior Questionnaire and the Infant‐Toddler Social and Emotional Assessment. A multivariate Cholesky Decomposition revealed three shared environmental factors, with one set of environmental influences common to competence, problem behavior, and physiological dysregulation, a second common to problem behavior and physiological dysregulation, and a third common to physiological dysregulation and NE. Also, there were two additive genetic factors, with one explaining variance in competence, NE, and a small amount of variance in problem behavior, and a second explaining variance in problem behavior and NE. Given the common shared environmental factors across outcomes, these results suggest that toddlerhood could be a particularly important time to intervene, as interventions could simultaneously improve competencies and reduce problem behaviors. This study also highlights the need for genetically informed research to examine the etiology of multiple outcomes and address overlap.
Seeking and avoiding intergroup contact: Future frontiers of research on building social integration
Authors: Paolini Stefania , Harwood Jake , Hewstone Miles , Neumann David L.
Published: November 2018

Over 60 years of research and comprehensive reviews now support Gordon Allport's contact hypothesis that face‐to‐face interactions between members of opposing groups should be promoted to lessen prejudice and improve intergroup relations. Society however does not yet enjoy the full prejudice‐reducing benefits of intergroup contact because opportunities for contact are often not taken up, and segregation persists in the face of diversity. In this article, we review recent investigations on the social psychology of individuals' seeking and avoiding intergroup contact and set the stage for new research in this area. We call for a new generation of research on intergroup contact that addresses a novel and critical research question: What personal, situational, and wider social factors move individuals towards or away from engaging in intergroup contact? This research can help us design intervention strategies to ensure that opportunities for, and benefits of, intergroup contact are fully enjoyed by individuals and groups in increasingly diverse societies.
Histone acetyltransferase GCN5 contributes to cell wall integrity and salt stress tolerance by altering the expression of cellulose synthesis genes
Authors: Zheng Mei , Liu Xingbei , Lin Jingchen , Liu Xinye , Wang Zhouying , Xin Mingming , Yao Yingyin , Peng Huiru , Zhou Dao‐Xiu , Ni Zhongfu , Sun Qixin , Hu Zhaorong
Published: November 2018

Excess soluble salts in soil are harmful to the growth and development of most plants. Evidence is emerging that the plant cell wall is involved in sensing and responding to salt stress, but the underlying mechanisms are not well understood. We reveal that the histone acetyltransferase General control non‐repressed protein 5 (GCN5) is required for the maintenance of cell wall integrity and salt stress tolerance. The levels of GCN5 mRNA are increased in response to salt stress. The gcn5 mutants exhibited severe growth inhibition and defects in cell wall integrity under salt stress conditions. Combining RNA sequencing and chromatin immunoprecipitation assays, we identified the chitinase‐like gene CTL1, polygalacturonase involved in expansion‐3 (PGX3) and MYB domain protein‐54 (MYB54) as direct targets of GCN5. Acetylation of H3K9 and H3K14 mediated by GCN5 is associated with activation of CTL1, PGX3 and MYB54 under salt stress. Moreover, constitutive expression of CTL1 in the gcn5 mutant restores salt tolerance and cell wall integrity. In addition, the expression of the wheat TaGCN5 gene in Arabidopsis gcn5 mutant plants complemented the salt tolerance and cell wall integrity phenotypes, suggesting that GCN5‐mediated salt tolerance is conserved between Arabidopsis and wheat. Taken together, our data indicate that GCN5 plays a key role in the preservation of salt tolerance via versatile regulation in plants.
Asymmetric effects of cultural institutes on trade and foreign direct investment
Authors: Lien Donald , Lo Melody , Bojanic David
Published: November 2018

The purpose of a cultural institute is to improve international relations with other countries by promoting language familiarity and cultural awareness. In addition, cultural institutes can provide additional business opportunities that lead to positive economic side effects such as increases in trade and foreign direct investment (FDI). In this study, gravity models were used to analyse the data for the Goethe Institut (Germany), the Cervantes Institute (Spain) and the Confucius Institute (China) to identify any stylised international patterns of the documented economic effects. The study finds significant positive effects on bilateral trade and FDI outflows for all three programmes, along with two important (i) the effects are stronger for non‐advanced economies and (ii) the effects are substantially larger on FDI than on trade. These results suggest that cultural institutes can be an effective policy tool in promoting FDI outflows, with the strongest effect realised when a home country locates its cultural institutes in host countries with developing economies. Importantly, results also suggest that the Chinese government's approach to extend its soft power through rapid expansion of Confucius Institutes worldwide has not been as successful as the efforts by the German Goethe Institut in increasing trade and FDI.
Temporalities and Rhythms of Living in Utría National Park, Colombia
Authors: Acosta García Nicolás
Published: November 2018

This photo essay investigates the political ecology of living in and around Utría National Park, in Colombia's Pacific coast region of Chocó. This area is home to Afro‐descendant and indigenous Embera communities. I use the emic concept of “rhythms” to explore networks and temporalities in subtle elements of pictures displaying local livelihoods, places of dwelling, environmental change, and conservation practices. While acknowledging the complex and difficult realities of this area, my aim is to make explicit the networks that, with their rhythms and temporalities, weave and mark the pace of everyday life in the villages. These, in turn, give space to reflect on practices of living with a damaged planet and a postcolonial order.
Age-related perceptual difference of Kyungsang Korean accent contrast: A diachronic observation
Authors: Lee Hyunjung
Published: November 2018

This study investigated the perception of lexical pitch accent contrasts between innovative and conservative listeners under a sound change. Younger and older listeners speaking Kyungsang Korean participated in the 2AFC identification task. The participants responded to stimuli systematically varying spectral and temporal F0 properties (i.e., peak duration, onset/peak F0 values) and talker voices (i.e., older vs younger talker). Results showed that younger listeners utilized the temporal cue differently from older listeners, and listeners' perception also varied by talker age. Discussion was made in terms of consistency between the perception and production and the effect of social information in speech perception.
Physiological, Genetic, and Transcriptomic Analysis of Alcohol-Induced Delay of
Escherichia coli
Death
Authors: Ferraro Christina M. , Finkel Steven E.
Published: November 2018

In one of the most well-studied organisms in the life sciences,
Escherichia coli
, we still do not fully understand what causes populations to die. This is largely due to the technological difficulties of studying bacterial cell death. This study provides an avenue to studying how and why
E. coli
populations, and perhaps other microbes, transition from stationary phase to death phase by exploring how ethanol and other alcohols delay the onset of death. Here, we demonstrate that alcohols are acting as signaling molecules to achieve the delay in death phase. This study not only offers a better understanding of a fundamental process but perhaps also provides a gateway to studying the dynamics between ethanol and microbes in the human gastrointestinal tract.
Congenital colonic stenosis with absent caecum and appendix: a rare association
Authors: Khanna Kashish , Yadav Devendra Kumar , Nandan Ruchira , Goel Prabudh , Srinivas Rao Potala
Published: November 2018

Congenital colonic stenosis is a rare condition with less than 20 cases reported in the literature since 1966. We report an interesting case of a 7-month-old baby girl who presented with features suggestive of acute intestinal obstruction. On exploration, it was a case of ascending colon stenosis with absence of caecum and appendix. A double barrel ileocolostomy was performed. The histopathology confirmed the diagnosis of colonic stenosis and ruled out the presence of Hirschsprung’s disease in the distal colon. The child underwent second stage surgery (stoma closure) after 9 months. In complex cases of congenital colonic stenosis, an early decompressive surgery followed by a delayed second stage closure is recommended in patients with poor general condition.
Cryoablation: a potential treatment option for renal metastasis from lung cancer?
Authors: Degn Stine , Davidsen Jesper Rømhild , Graumann Ole
Published: November 2018

Cryoablation is successfully performed as a treatment for small renal cancers. The occurrence of a solitary renal metastasis from lung cancer is an uncommon finding entailing a limited knowledge on the choice of its optimal treatment. We present two patients diagnosed with non-small cell lung cancer, who were initially treated with curatively intended chemoradiotherapy. In the follow-up period, a non-symptomatic solitary renal metastasis was found in both patients. Both received CT-guided cryoablation of their renal metastases. One patient was successfully treated with no relapse, whereas the other patient received re-cryoablation due to development of a new renal metastasis. In both patients, no residual tumour was found at the 3 months’ follow-up examination. Whether the minimally invasive procedure of cryoablation is a feasible treatment in the management of solitary renal metastases from lung cancer is still undetermined. The recurrence and incomplete treatment are concerns requiring further research.
Central serous chorioretinopathy in a patient of juxtapapillary excavation misdiagnosed as optic disc pit maculopathy
Authors: Kumawat Devesh , Anjum Shahnaz , Sahay Pranita , Chawla Rohan
Published: November 2018

A 29-year-old healthy man had blurring of vision in the left eye for the past 2 months and was referred for the surgical management of optic disc pit maculopathy. Colour fundus examination and optical coherence tomography (OCT) revealed a large deep retinochoroidal excavation close to the temporal edge of the optic disc with an isolated central neurosensory detachment at the macula with underlying multiple small pigment epithelium detachments in the absence of retinoschisis. Fundus fluorescein angiography (FFA) confirmed the presence of multi-focal leakage at the macula and pooling into subretinal space in the form of a ‘smoke-stack’. A correct diagnosis of juxtapapillary excavation and central serous chorioretinopathy was made and lifestyle modifications were advised in view of the acute episode. The clinical signs, OCT and FFA feature helped in the differentiation and appropriate management of maculopathy in this case.
Association between normal tension glaucoma and the risk of Alzheimer’s disease: a nationwide population-based cohort study in Taiwan
Authors: Chen Yu-Yen , Lai Yun-Ju , Yen Yung-Feng , Shen Ying-Cheng , Wang Chun-Yuan , Liang Chiao-Ying , Lin Keng-Hung , Fan Lir-Wan
Published: November 2018

Objectives

To investigate a possible association between normal tension glaucoma (NTG) and an increased risk of developing Alzheimer’s disease (AD).

Design

Retrospective cohort study.

Setting

NTG group and the comparison group were retrieved from the whole population of the Taiwan National Health Insurance Research Database from 1 January 2001 to 31 December 2013.

Participants

A total of 15 317 subjects with NTG were enrolled in the NTG group, and 61 268 age-matched and gender-matched subjects without glaucoma were enrolled in the comparison group.

Primary and secondary outcome measures

Kaplan-Meier curves were generated to compare the cumulative hazard of AD between the two groups. A multivariable Cox regression analysis was used to estimate the adjusted hazard ratios (HRs) of AD, adjusted for diabetes, hypertension, hyperlipidaemia, coronary artery disease and stroke. Furthermore, risk factors for developing AD among the NTG group were investigated.

Results

The mean age of the cohort was 62.1±12.5 years. Patients with NTG had significantly higher proportions of diabetes, hypertension, hyperlipidaemia, coronary artery disease and stroke than the comparisons. Patients with NTG had a significantly higher cumulative hazard for AD than the comparisons (p<0.0001). In the multivariable Cox regression after adjustment for confounders, the NTG group had a significantly higher risk of AD (adjusted HR 1.52; 95% CI 1.41 to 1.63). Moreover, in the NTG group, when we compared the effects of different types of glaucoma eye drops, none of the eye drops used were significant risk factors or protective factors for AD.

Conclusions

People with NTG are at a significantly greater risk of developing AD compared with individuals without glaucoma. Among patients with NTG, none of the glaucoma eye drops used significantly changed the risk of subsequent AD.
Comparing pharmacological venous thromboembolism prophylaxis to intermittent pneumatic compression in acute intracerebral haemorrhage: protocol for a systematic review and network meta-analysis
Authors: Yogendrakumar Vignan , Lun Ronda , Hutton Brian , Fergusson Dean A , Dowlatshahi Dar
Published: November 2018

Introduction

Patients with an intracerebral haemorrhage are at increased risk of venous thromboembolism. Pharmacotherapy and pneumatic compression devices are capable of preventing venous thromboembolism, however both interventions have limitations. There are no head-to-head comparisons between these two interventions. To address this knowledge gap, we plan to perform a systematic review and network meta-analysis to examine the comparative effectiveness of pharmacological prophylaxis and mechanical compression devices in the context of intracerebral haemorrhage.

Methods and analysis

MEDLINE, PUBMED, EMBASE, CENTRAL, ClinicalTrials.gov and the Internet Stroke Trials Registry will be searched with assistance from an experienced information specialist. Eligible studies will include those that have enrolled adults presenting with spontaneous intracerebral haemorrhage and compared one or more of the respective interventions against each other and/or a control. Primary outcomes to be assessed are occurrence of new venous thromboembolism (deep vein thrombosis and/or pulmonary embolism) and haematoma expansion, defined as a significant enlargement of baseline haemorrhage or new haemorrhage occurrence. Both randomised and non-randomised comparative studies will be included. Data on participant characteristics, study design, intervention details and outcomes will be extracted. Study quality will be assessed using the Cochrane Risk of Bias Tool and the Robins-I tool. Bayesian network meta-analyses will be performed to compare interventions based on all available direct and indirect evidence. If the transitivity assumption for network meta-analysis cannot be met, we will perform a qualitative assessment.

Ethics and dissemination

Formal ethics is not required as primary data will not be collected. The findings of this study will be disseminated through conference presentations, and peer-reviewed publications. In an area of clinical practice where equipoise exists, the findings of this study may assist in determining which treatment intervention is most effective in venous thromboembolism prevention.

PROSPERO registration number

CRD42018090960.
Combating pancreatic cancer with PI3K pathway inhibitors in the era of personalised medicine
Authors: Conway James RW , Herrmann David , Evans TR Jeffry , Morton Jennifer P , Timpson Paul
Published: November 2018

Pancreatic ductal adenocarcinoma (PDAC) is among the most deadly solid tumours. This is due to a generally late-stage diagnosis of a primarily treatment-refractory disease. Several large-scale sequencing and mass spectrometry approaches have identified key drivers of this disease and in doing so highlighted the vast heterogeneity of lower frequency mutations that make clinical trials of targeted agents in unselected patients increasingly futile. There is a clear need for improved biomarkers to guide effective targeted therapies, with biomarker-driven clinical trials for personalised medicine becoming increasingly common in several cancers. Interestingly, many of the aberrant signalling pathways in PDAC rely on downstream signal transduction through the mitogen-activated protein kinase and phosphoinositide 3-kinase (PI3K) pathways, which has led to the development of several approaches to target these key regulators, primarily as combination therapies. The following review discusses the trend of PDAC therapy towards molecular subtyping for biomarker-driven personalised therapies, highlighting the key pathways under investigation and their relationship to the PI3K pathway.
Mild cognitive impairment in primary care: a clinical review
Authors: Assaf Georges , Tanielian Maria
Published: November 2018

Dementia is projected to become a global health priority but often not diagnosed in its earlier preclinical stage which is mild cognitive impairment (MCI). MCI is generally referred as a transition state between normal cognition and Alzheimer’s disease. Primary care physicians play an important role in its early diagnosis and identification of patients most likely to progress to Alzheimer’s disease while offering evidenced-based interventions that may reverse or halt the progression to further cognitive impairment. The aim of this review is to introduce the concept of MCI in primary care through a case-based clinical review. We discuss the case of a patient with MCI and provide an evidence-based framework for assessment, early recognition and management of MCI while addressing associated risk factors, neuropsychiatric symptoms and prognosis.
DAPSA and ultrasound show different perspectives of psoriatic arthritis disease activity: results from a 12-month longitudinal observational study in patients starting treatment with biological disease-modifying antirheumatic drugs
Authors: Pukšić Silva , Bolton-King Pernille , Sexton Joseph , Michelsen Brigitte , Kvien Tore K , Berner Hammer Hilde
Published: November 2018

Objectives

Disease Activity index for PSoriatic Arthritis (DAPSA) (sum score 68/66 tender/swollen joint counts (68TJC/66SJC), patient’s global assessment, pain and C-reactive protein (CRP)) is recommended for clinical assessment of disease activity in patients with psoriatic arthritis (PsA). Ultrasound (US) (grey scale (GS) and power Doppler (PD)) detects inflammation in joints and extra-articular structures. The present objectives were to explore the longitudinal relationships between DAPSA, clinical assessment as well as patient-reported outcome measures (PROMs) with US in patients with PsA initiating biological DMARDs and the associations between DAPSA and US remission.

Methods

47 patients with PsA were examined at baseline and after 3, 6, 9 and 12 months. Assessments included 68TJC/66SJC, examiner’s global assessment (EGA), PROMs, CRP, erythrocyte sedimentation rate (ESR) and US GS and PD (48 joints, 10 flexor tendons, 14 entheses, 4 bursae). Clinical composite scores and PD sum scores (0=remission) were calculated. Longitudinal associations were explored by generalised estimating equations with linear and logistic regression.

Results

DAPSA was not longitudinally associated to PD. 66SJC, ESR, 28-joint Disease Activity Score, EGA and CRP were longitudinally associated with PD (p<0.001–0.03), whereas the pain-related components of DAPSA (68TJC and pain) as well as PROMs were not associated. At 6–12 months, remission was achieved in 29%–33 % of the patients for DAPSA and 59%–70 % for PD. The association between DAPSA and PD remission was not significant (p=0.33).

Conclusions

DAPSA was not associated with US inflammatory findings which indicates that DAPSA and US may assess different aspects of PsA activity.
Comparison of trauma outcomes between Japan and the USA using national trauma registries
Authors: Matsumoto Shokei , Jung Kyoungwon , Smith Alan , Yamazaki Motoyasu , Kitano Mitsuhide , Coimbra Raul
Published: November 2018

Background

The National Trauma Data Bank (NTDB) has served as a global benchmark for trauma care quality and outcomes. Herein, we compared patient characteristics, trauma management, and outcomes between Japanese emergency and critical care centers and US level 1 trauma centers using the Japanese Trauma Data Bank (JTDB) and NTDB.

Methods

A retrospective cohort matching (1:1) study was performed. Patients treated in 2013 with an Injury Severity Score ≥9 were included. The primary outcome measure was in-hospital mortality. The secondary outcome measures included the hospital length of stay and the rate of use of radiological diagnostic modalities.

Results

A total of 14 960 pairs with well-balanced characteristics were generated from 22 535 and 112 060 eligible patients in the JTDB and NTDB, respectively. Before matching, the in-hospital mortality was higher in the JTDB than in the NTDB (7.6% vs. 6.1%; OR, 1.28; 95% CI 1.21 to 1.35). However, after matching, the in-hospital mortality was lower in the JTDB cohort (4.2% vs. 5.8%; OR, 0.72; 95% CI 0.65 to 0.80). CT scans were used in >80% of JTDB patients, which was more than 1.5 times as often as the use in the NTDB cohort. In subgroup analyses, only patients who received a blood transfusion had a poorer survival outcome in the JTDB compared with the NTDB (OR, 1.32; 95% CI 1.07 to 1.64).

Discussion

We observed marked differences in trauma care between Japan and the USA. Although the quality of the recent Japanese trauma care appears to be approaching that of the USA, it may be further improved, such as by the establishment of transfusion protocols.

Level of evidence

Level IV.
Anti-adhesion of probiotic Enterococcus faecium WEFA23 against five pathogens and the beneficial effect of its S-layer proteins against Listeria monocytogenes
Authors: He Yao , Xu Xiongpeng , Zhang Fen , Xu Di , Liu Zhengqi , Tao Xueying , Wei Hua
Published: November 2018

Enterococcus faecium WEFA23 is a potential probiotic strain isolated from Chinese infant feces. In this study, the antagonistic activity of E. faecium WEFA23 on adhesion to pathogens was investigated. Enterococcus faecium WEFA23 was able to compete, exclude, and displace the adhesion of Escherichia coli O157:H7, Salmonella Typhimurium ATCC 13311, Listeria monocytogenes CMCC54007, Staphylococcus aureus CMCC26003, and Shigella sonnei ATCC 25931 to Caco-2 cells. Among them, L. monocytogenes achieved the strongest inhibition rate in both competition and displacement assays. Those anti-adhesion capacities were related to the bacterial physicochemical properties (hydrophobicity, auto-aggregation, and co-aggregation) of the bacterial surface. For L. monocytogenes, the anti-adhesion capacity was affected by the heat treatment, cell density, and growth phase of E. faecium WEFA23; 108 colony-forming units of viable cells per millilitre at the stationary phase exhibited the strongest anti-adhesion activity. In addition, removal of S-layer proteins of E. faecium WEFA23 by treatment with 5 mol/L LiCl significantly decreased its adhesion capacity, and those S-layer proteins were able to compete, displace, and exclude L. monocytogenes at different levels. Both cells and S-layer proteins of E. faecium WEFA23 significantly reduced the apoptosis of Caco-2 cells induced by L. monocytogenes, which was mediated by caspase-3 activation. This study might be helpful in understanding the anti-adhesion mechanism of probiotics against pathogens.
A real-time PCR regimen for testing environmental samples for Salmonella enterica subsp. enterica serovars of concern to the poultry industry, with special focus on Salmonella Enteritidis
Authors: Nadin-Davis S. , Pope L. , Ogunremi D. , Brooks B. , Devenish J.
Published: November 2018

A real-time PCR (qPCR) regimen, using up to six genetic targets, was developed to rapidly detect Salmonella and in particular identify Salmonella Enteritidis. The test regimen was first evaluated using a reference culture collection of Salmonella to confirm the appropriateness of the selected targets, which included up to three genetic markers for discrimination of Salmonella Enteritidis from other Salmonella serovars commonly found in poultry facilities. The qPCR procedure was then compared with culture methods used to detect Salmonella using a collection of enrichment broths previously generated from 239 environmental samples collected from a large number of hatchery facilities across Canada over several years. The qPCR regimen facilitated specific detection of Salmonella Enteritidis, and on a sample basis, it showed excellent agreement with the culture methods. Moreover, in many cases, qPCR detected Salmonella earlier in the culture process than did the culture method. Application of this method will significantly shorten test times and allow more timely identification of infected poultry premises, thereby improving present programmes aimed at controlling Salmonella Enteritidis at the environmental source.
Estimating Quantum Statistical Parton Distribution Functions in proton by maximum entropy method
Authors: Sohaily Sozha
Published: November 2018

An attempt to extend simple Parton Distribution Functions based on the quantum statistical model to consider more active flavors is presented here. Considering partons as clusters, inspiring from the static picture of proton composed of three valence quarks, such a reasonable extension is surveyed to improve the results. Analytic expressions for the longitudinal Quantum Statistical Parton Distribution Functions are obtained by applying the maximum entropy principle beside theoretical proton sum rules. Furthermore, the main purpose of this study is to predict a minimum energy scale to probe the proton with a defined condition, theoretically. An interesting approach to determine the statistical variables exactly without fitting and fixing is employed and the consistency of computed distributions with the experimental observations gives a robust confirm of presented simple statistical model.
THE IMPACT OF IT ASSETS ON INNOVATION PERFORMANCE – THE MEDIATING ROLE OF DEVELOPMENTAL CULTURE AND ABSORPTIVE CAPACITY
Authors: STOFFELS MARIUS , LEKER JENS
Published: November 2018

Information technology (IT) has been acknowledged as a driver of innovation performance and scholars agree that the impact of IT is mediated by additional organisational factors. Among those mediators between IT and innovation performance, a firm’s absorptive capacity and developmental culture received considerable attention. Empirical evidence suggests that both fully mediate the impact of IT on innovation performance; however, research that jointly considers both dimensions is scarce. Thus, we follow the resource-based view to operationalise IT assets, absorptive capacity, and developmental culture in one research model and apply SEM to test it with a sample of 58 firms from the water industry in Germany. We find simultaneous full mediation effects for both mediators. The fact that both mediation effects are significant in the presence of each other indicates that absorptive capacity and developmental culture explain complementary portions of the variance in innovation performance — a finding we relate to sociomateriality theory.
The aftermath of the CPE and the Carnian–Norian transition in northwestern Sichuan Basin, South China
Authors: Jin Xin , McRoberts Christopher A. , Shi Zhiqiang , Mietto Paolo , Rigo Manuel , Roghi Guido , Manfrin Stefano , Franceschi Marco , Preto Nereo
Published: November 2018

The northwestern Sichuan Basin (South China) was a portion of eastern Tethys where, during the Late Triassic, a sharp lithological transition from oolitic–bioclastic limestones and sponge reef mounds to dark grey terrigenous clays, siltstones and sandstones is visible in several localities. The timing and significance of this major facies transition is still unclear. Here we report new biostratigraphic and carbon stable isotope data from Hanwang and Jushui, northwestern Sichuan Basin. Sporomorphs, ammonoids, conodonts and halobiid bivalves show that the lithological change is Late Carnian to Early Norian in age. This amended age determination facilitates recalibration of the magnetostratigraphy in the area allowing correlation between the Late Triassic of the Sichuan Basin and the Astrochronostratigraphic Polarity Time Scale. A carbon stable isotopic perturbation across the Carnian–Norian Boundary (CNB) is missing in our sections, or it is concealed because of the mixed organic matter sources. Our findings pinpoint the position of the CNB to a short stratigraphic interval of
c.
12 m thickness in the Sichuan Basin. The studied sections greatly extend the palaeogeographical documentation of the CNB and provide novel information on biostratigraphy and chemostratigraphy that should be considered in defining the best position of the Norian Global Stratotype Section and Point.
Site investigation and use of artificial neural networks to predict rock permeability at the Siazakh Dam, Iran
Authors: Akbarimehr Davood , Aflaki Esmail
Published: November 2018

A detailed geostructural characterization (i.e. joint aperture, spacing, filling materials and joint size) was performed to evaluate the weathered rock foundation of the Siazakh Dam site, western Iran. Rock qualities were assigned a rock mass rating classification. A positive correlation was detected between permeability and rock characteristics, and played an important role in assessing fracture media. The joint aperture had a stronger relationship to joint permeability than did other fracture characteristics. The results strongly support the contention that a new generation of permeability equations and analytical methods may be obtained in accordance with a site's geological features. In this regard an artificial neural network (ANN) is a biologically inspired computing method that is capable of predicting the permeability values of rock masses with high accuracy. ANNs showed great potential in interpreting raw data from the Lugeon test and predicting the final permeability of a test section in a borehole. A new practical approach for the evaluation of field permeability with depth in fractured rock masses is also presented.
Determining constraints imposed by salt fabrics on the morphology of solution-mined energy storage cavities, through dissolution experiments using brine and seawater in halite
Authors: Field L. P. , Milodowski A. E. , Evans D. , Palumbo-Roe B. , Hall M. R. , Marriott A. L. , Barlow T. , Devez A.
Published: November 2018

Large-scale compressed air energy storage facilities offer one solution to the UK's energy demands, using solution-mined caverns in salt lithologies. For optimum gas storage efficiency, cavern geometry should ideally be smooth: spherical to cylindrical with a circular cross-section. However, such caverns are often irregular with marked asymmetry or ellipticity, and although the reasons for non-circular cross-sections developing during solution mining in some caverns can be related to, for example, the presence of interbedded lithologies, in other instances they are not fully understood. Cavities from dissolution experiments using five main end-member salt facies fabrics from the Triassic Preesall and Northwich Halite formations have been assessed to determine factors affecting cavity geometry, formation and variability in dissolution behaviour. Identical sets of experiments were performed on each fabric type, using two solution concentration strengths: brine and synthetic seawater. Comparison of experimental results using a combination of analytical and imaging techniques shows the extent to which the salt fabric and enhancement of features within the salt influence the resulting dissolution cavity. Observations show a visible increase in micropores within the adjacent halite matrix following dissolution. Smaller-scale features provide further insights into the dissolution processes, and salt fabric behaviour under different dissolution conditions.

Supplementary material:
A detailed description of methods is available at
https://doi.org/10.6084/m9.figshare.c.4282454