bluuebunny/crossref_metadata_2025 huggingface dataset:
First record of Mesozoic scroll coprolites: classification, characteristics, elemental composition and probable producers
Authors: Rakshit Nibedita , Bhat Mohd Shafi , Mukherjee Debarati , Ray Sanghamitra
Published: December 2018

Multiple, small, cylindrical scroll coprolites having rounded and tapering ends and pertaining to a new ichnotaxon have been recovered from the Upper Triassic Tiki Formation of India. This is the first record of scroll coprolites from the Mesozoic. Based on cross‐sectional geometry, external surface textures, and internal morphology, these coprolites are subdivided into three morphotypes. The coprolites contain several kinds of undigested food material in the form of ganoid fish scales, teeth, lower jaw and skeletal remains of various osteichthyans, chondrichthyans, archosauriforms and indeterminate reptiles. These inclusions are embedded in the groundmass separated by thin mucosal layers. The groundmass contains abundant gas vesicles, and secondarily‐filled shrinkage cracks. EDS analysis shows that the overall composition of the coprolites reflects Ca, P, C and O, suggesting calcium phosphate mineralogy, though other elements such as Fe, Mn, Al, Si are present in lesser proportions. Based on their similarity with the scrolled faeces of extant euryhaline hammerhead sharks, it is deduced that these coprolites were produced by euryhaline hybodontid sharks. At least two hybodontid taxa, Lonchidion and Pristrisodus, show high prevalence in the Tiki vertebrate fauna, suggesting that these were the possible producers. As the coprolite inclusions contain remains of other aquatic animals, these carnivorous hybodonts constituted the dominant predators of the Tiki aquatic ecosystem.
Incidence of adverse events attributable to bupivacaine liposome injectable suspension or plain bupivacaine for postoperative pain in pediatric surgical patients: A retrospective matched cohort analysis
Authors: Cohen Barak , Glosser Logan , Saab Remie , Walters Michael , Salih Ahmed , Zafeer‐Khan Mohammad , Rivas Eva , Zhang Kan , Schacham Nadav Y. , Chodavarapu Praneeta , Essber Hani , Chelnick David , Raza Syed , Hanline CeCelia , Khoshknabi Dilara , Yang Dongsheng , Seif John , Chhabada Surendrasingh , Turan Alparslan
Published: December 2018

Background

Surgical wound infiltration with local anesthetics is common as part of multimodal analgesia and enhanced recovery pathways in pediatric surgical patients. Liposomal bupivacaine can provide up to 92 hours of pain relief, and was approved by the U.S Food and Drug Administration for local infiltration in adults. It is also commonly used by pediatric surgeons, but its safety profile in this age group has not been described.

Aims

The aim of this study was to describe the incidence of local anesthetic systemic toxicity syndrome in pediatric surgical patients receiving liposomal bupivacaine compared to plain bupivacaine for surgical wound infiltration.

Methods

We conducted a retrospective, single center, assessor blinded cohort study of pediatric surgical inpatients having open or laparoscopic surgery in the Cleveland Clinic between 2013 and 2017 and receiving wound infiltration with local anesthetics. We compared the incidence of local anesthetic systemic toxicity among those who received any dose of liposomal bupivacaine and those who received plain bupivacaine. Groups were matched 1:2 according to procedure type, age, and physical status score. Local anesthetic systemic toxicity was primarily defined as at least two signs or symptoms possibly related to anesthetic toxicity, as judged by two independent adjudicators blinded to the type of local anesthetic. A sensitivity analysis compared the incidence of a single sign/symptom possibly related to anesthetic toxicity.

Results

A total of 924 surgical cases were included in the final analysis (356 liposomal bupivacaine and 568 plain bupivacaine cases). The primary outcome did not occur in any patient. The sensitivity analysis found three cases in the liposomal bupivacaine group and two cases in the plain bupivacaine group having a single sign/symptom possibly related to local anesthetic administration (relative risk 2.4, 95% CI 0.4‐14.0, P = 0.38).

Conclusion

In a cohort of pediatric surgical patients receiving wound infiltration with either plain or liposomal bupivacaine, we identified no cases of local anesthetic systemic toxicity syndrome, and only few patients with any sign or symptom that could potentially be related to local anesthetic toxicity.
Efficient production of antifungal proteins in plants using a new transient expression vector derived from tobacco mosaic virus
Authors: Shi Xiaoqing , Cordero Teresa , Garrigues Sandra , Marcos Jose F. , Daròs José‐Antonio , Coca María
Published: December 2018

Fungi that infect plants, animals or humans pose a serious threat to human health and food security. Antifungal proteins (AFPs) secreted by filamentous fungi are promising biomolecules that could be used to develop new antifungal therapies in medicine and agriculture. They are small highly stable proteins with specific potent activity against fungal pathogens. However, their exploitation requires efficient, sustainable and safe production systems. Here, we report the development of an easy‐to‐use, open access viral vector based on Tobacco mosaic virus (TMV). This new system allows the fast and efficient assembly of the open reading frames of interest in small intermediate entry plasmids using the Gibson reaction. The manipulated TMV fragments are then transferred to the infectious clone by a second Gibson assembly reaction. Recombinant proteins are produced by agroinoculating plant leaves with the resulting infectious clones. Using this simple viral vector, we have efficiently produced two different AFPs in Nicotiana benthamiana leaves, namely the Aspergillus giganteus AFP and the Penicillium digitatum AfpB. We obtained high protein yields by targeting these bioactive small proteins to the apoplastic space of plant cells. However, when AFPs were targeted to intracellular compartments, we observed toxic effects in the host plants and undetectable levels of protein. We also demonstrate that this production system renders AFPs fully active against target pathogens, and that crude plant extracellular fluids containing the AfpB can protect tomato plants from Botrytis cinerea infection, thus supporting the idea that plants are suitable biofactories to bring these antifungal proteins to the market.
The effectiveness of topical therapy combined with 308‐nm excimer laser on vitiligo compared to excimer laser monotherapy in pediatric patients
Authors: Li Lili , Liang Yanping , Hong Jiqiong , Lan Lizhen , Xiao Hewei , Xie Zhi
Published: December 2018

We evaluated the efficiency of using a 308‐nm excimer laser with either tacrolimus, pimecrolimus, or halometasone for the treatment of childhood vitiligo. Patients who received combined treatments had significantly higher rates of repigmentation in comparison with individuals who underwent excimer laser alone therapy. Moreover, patients who received treatment with excimer laser and halometasone had significantly higher rates of repigmentation, even higher than individuals who were treated with tacrolimus combined or pimecrolimus combined. This regimen was more effective on the face, neck, and limbs. We conclude that the use of a combined excimer laser and halometasone cream has a greater therapeutic effect than laser alone.
Chlorogenic acid‐mediated chemical defence of plants against insect herbivores
Authors: Kundu A. , Vadassery J.
Published: December 2018

Chlorogenic acid is one of the most abundant beneficial polyphenols in plants and is well known as a nutritional antioxidant in plant‐based foods. Apart from its dietary antioxidant activity, it has been proved to be an efficient defence molecule against a broad range of insect herbivores. In the last two decades, several reports have shown the effectiveness of chlorogenic acid in insect growth deterrence. The pathway for chlorogenic acid biosynthesis in plants was previously elucidated, and metabolic engineering of the principal pathway showed high chlorogenic acid production in tomato plants. Herbivore‐mediated induction of chlorogenic acid biosynthesis was also demonstrated both at metabolite and transcript level, although herbivore‐mediated molecular regulation of chlorogenic acid biosynthesis is not yet fully elucidated. In this communication, we present our views on the efficacy of chlorogenic acid as an anti‐herbivore defence molecule in plants and also discuss its future outlook.
Voting “Against Islamization”? How Anti‐Islamic Right‐Wing, Populist Political Campaign Ads Influence Explicit and Implicit Attitudes Toward Muslims as Well as Voting Preferences
Authors: Schmuck Desirée , Matthes Jörg
Published: December 2018

We explore the effects of anti‐Islamic right‐wing, populist political campaign ads on voting intention for a right‐wing populist party using a quota‐based online experiment (N = 174). Additionally, we investigate implicit attitudes (i.e., automatic affective associations) and explicit attitudes (i.e., overtly expressed evaluations) toward Muslims as underlying mechanisms of these effects. We find that exposure to the political campaign ads prompts explicit hostile attitudes toward Muslims mediated by implicit attitudes. Explicit attitudes in turn shape voting intention. Moreover, implicit attitudes toward Muslims predict voting preference beyond the influence of explicit attitudes. Thus, resentments toward Muslims may foster voters’ support for anti‐Islamic right‐wing populist parties even “under the radar” of conscious awareness. In sum, this study demonstrates for the first time the entire process of right‐wing, populist political campaign ads’ effects on voting preferences via implicit and explicit attitudes toward Muslims.
Dispatches From Along the Veil: Stories of Racial Rejection
Authors: Hughey Matthew W.
Published: December 2018

In the wake of both long‐standing frustration with, and objective levels of, race, gender, and class exclusion in academic societies, I dive into a professional diary I have collected over the years. I demonstrate nine interactional patterns culled from my own experiences alongside the Du Boisian “veil.” Such social forces are often considered esoteric and inaccessible due to racial hierarchies, elite gatekeeping, and methodological constraints. I read these patterns as mechanisms in the reproduction of a racialized interaction order. That order both creates, and is bolstered by, systematic discrimination, disciplined exclusion, and constricted knowledge production.
Tearing behaviour of two types of leather: A comparative study carried out at the local scale using the full kinematic and thermal field measurement techniques
Authors: Di Cesare Noëlie , Corvec Guillaume , Le Cam Jean‐Benoît , Balandraud Xavier , Gauffreteau Julien
Published: December 2018

Leather materials undergo various strain and stress states during their elaboration process and their application in numerous different functions. Among the key properties required for such materials, tearing resistance appears as one of the most important. In this paper, the tearing behaviour of two types of leather, a grain pigskin leather and a grain calf leather, was investigated at the local scale using the full‐field techniques. During the tests, thermal fields were measured at the surface of the two leathers by means of an infrared camera. Measurements of the displacement and deformation fields were also performed at the surface of the pigskin sample using the digital image correlation technique, which was not possible for the calf sample due to surface wrinkling. The results obtained enable us to discuss and compare the tearing resistance of both leathers in terms of the thermal activity in the zone of influence of the crack. The best tearing resistance was obtained for the grain calf leather that has undergone a retanning operation and whose matrix contained a plasticiser.
Irritative potency of selected wound antiseptics in the hen's egg test on chorioallantoic membrane to predict their compatibility to wounds
Authors: Harnoss Julian Camill , Elrub Qasim Mahmoud Abu , Jung Jin‐On , Koburger Torsten , Assadian Ojan , Dissemond Joachim , Baguhl Romy , Papke Roald , Kramer Axel ,   Supported by the Working Group Antiseptics of the International Society of Chemotherapy for Infection and Cancer (ISC)
Published: December 2018

Antiseptics are being used for prevention of infections in acute wounds and for treatment of infections in acute and chronic wounds. However, some antiseptics’ high tissue toxicity might delay the healing process. The aim of this study was to investigate the tissue toxicity of preferentially used wound antiseptics and the influence of antiphlogistic additives via the hen's egg test on the chorioallantoic membrane (HET‐CAM). The HET‐CAM is a semi‐in‐vivo method testing the tissue tolerability of wound antiseptics by evaluating the blood vessel reaction of the chorioallantoic membrane in terms of hemorrhage, vessel lysis, and coagulation. For each test day, selected test substances were applied on the membranes of two to three eggs according to the test protocol. The overall irritation was then evaluated by referring to a calculated score. Normal distribution of the resulting scores was confirmed by D'Agostino‐Pearson omnibus K2 test. Significant differences between the antiseptics were calculated by Tukey's multiple comparisons test. Severe CAM reactions were observed after short‐term application of octenidine based wound gel (0.05%) and chlorhexidine digluconate (0.5% solution), moderate reactions for octenidine (0.05%) in aqueous solution combined with dexpanthenol (1.34%) and allantoin (0.2%) or for hydrogen peroxide (1.5% and 0.5%) in aqueous solution, slight reactions were observed for hydrogen peroxide (1.5%) in aqueous solution in combination with sodium thiocyanate (0.698%) and for the combination of NaOCl/HOCl (each 0.004%). Polyhexanide (0.04%) in Ringer solution and polyhexanide (0.05%) in Lipofundin, the hemoglobin spray (10%), dexpanthenol, and allantoin showed no irritation. The HET‐CAM qualifies as a primary screening test for tissue tolerance of wound antiseptics. Regarding local tolerability, polyhexanide and hypochlorite are superior to other antiseptics.
Numerical Analysis of Second-Order Mean Wave Forces by a Stabilized Higher-Order Boundary Element Method
Authors: Shao Yan-Lin
Published: December 2018

A stabilized higher-order boundary element method (HOBEM) based on cubic shape functions is presented to solve the linear wave-structure interaction with the presence of steady or slowly varying velocities. The m-terms which involve second derivatives of local steady flow are difficult to calculate accurately on structure surfaces with large curvatures. They are also not integrable at the sharp corners. A formulation of the boundary value problem in a body-fixed coordinate system is thus adopted, which avoids the calculation of the m-terms. The use of body-fixed coordinate system also avoids the inconsistency in the traditional perturbation method when the second-order slowly varying motions are larger than the first-order motions. A stabilized numerical method based on streamline integration and biased differencing scheme along the streamlines will be presented. An implicit scheme is used for the convective terms in the free surface conditions for the time integration of the free surface conditions. In an implicit scheme, solution of an additional matrix equation is normally required because the convective terms are discretized by using the variables at current time-step rather than that from the previous time steps. A novel method that avoids solving such matrix equation is presented, which reduces the computational efforts significantly in the implicit method. The methodology is applicable on both structured and unstructured meshes. It can also be used in general second-order wave-structure interaction analysis with the presence of steady or slowly varying velocities.
Convergent evolution of a metabolic switch between aphid and caterpillar resistance in cereals
Authors: Li B. , Förster C. , Robert C. A. M. , Züst T. , Hu L. , Machado R. A. R. , Berset J.-D. , Handrick V. , Knauer T. , Hensel G. , Chen W. , Kumlehn J. , Yang P. , Keller B. , Gershenzon J. , Jander G. , Köllner T. G. , Erb M.
Published: December 2018

Maize and wheat independently evolved the capacity to control plant defenses through
O
-methylation of regulatory benzoxazinoids.
Applying ecological resistance and resilience to dissect bacterial antibiotic responses
Authors: Meredith Hannah R. , Andreani Virgile , Ma Helena R. , Lopatkin Allison J. , Lee Anna J. , Anderson Deverick J. , Batt Gregory , You Lingchong
Published: December 2018

Applying an ecological framework to bacterial antibiotic responses improves understanding of population recovery.
Rift Valley fever virus induces fetal demise in Sprague-Dawley rats through direct placental infection
Authors: McMillen Cynthia M. , Arora Nitin , Boyles Devin A. , Albe Joseph R. , Kujawa Michael R. , Bonadio Jeffrey F. , Coyne Carolyn B. , Hartman Amy L.
Published: December 2018

Rift Valley fever virus infection of pregnant rats results in fetal infection and death, even in dams with no signs of illness.
Spin transport in a Mott insulator of ultracold fermions
Authors: Nichols Matthew A. , Cheuk Lawrence W. , Okan Melih , Hartke Thomas R. , Mendez Enrique , Senthil T. , Khatami Ehsan , Zhang Hao , Zwierlein Martin W.
Published: December 2018

Simulating transport with cold atoms

Much can be learned about the nature of a solid from how charge and spin propagate through it. Transport experiments can also be performed in quantum simulators such as cold atom systems, in which individual atoms can be imaged using quantum microscopes. Now, two groups have investigated transport in the so-called Fermi-Hubbard model using a two-dimensional optical lattice filled with one fermionic atom per site (see the Perspective by Brantut). Moving away from half-filling to enable charge transport, Brown
et al.
found that the resistivity had a linear temperature dependence, not unlike that seen in the strange metal phase of cuprate superconductors. In a complementary study on spin transport, Nichols
et al.
observed spin diffusion driven by superexchange coupling.

Science
, this issue p.
379
, p.
383
; see also p.
344
Noninvasive
11
C-rifampin positron emission tomography reveals drug biodistribution in tuberculous meningitis
Authors: Tucker Elizabeth W. , Guglieri-Lopez Beatriz , Ordonez Alvaro A. , Ritchie Brittaney , Klunk Mariah H. , Sharma Richa , Chang Yong S. , Sanchez-Bautista Julian , Frey Sarah , Lodge Martin A. , Rowe Steven P. , Holt Daniel P. , Gobburu Jogarao V. S. , Peloquin Charles A. , Mathews William B. , Dannals Robert F. , Pardo Carlos A. , Kannan Sujatha , Ivaturi Vijay D. , Jain Sanjay K.
Published: December 2018

PET reveals spatially heterogeneous rifampin brain penetration, which decreases rapidly with treatment during tuberculous meningitis.
Diverse Vectors and Mechanisms Spread New Delhi Metallo-β-Lactamases among Carbapenem-Resistant
Enterobacteriaceae
in the Greater Boston Area
Authors: Pecora Nicole , Zhao Xiaomin , Nudel Kathleen , Hoffmann Maria , Li Ning , Onderdonk Andrew B. , Yokoe Deborah , Brown Eric , Allard Marc , Bry Lynn
Published: December 2018

New Delhi metallo-beta-lactamases (NDMs) are an uncommon but emerging cause of carbapenem resistance in the United States. Genomic factors promoting their domestic spread remain poorly characterized.
Loss of Function in Escherichia coli Exposed to Environmentally Relevant Concentrations of Benzalkonium Chloride
Authors: Forbes Sarah , Morgan Nicola , Humphreys Gavin J. , Amézquita Alejandro , Mistry Hitesh , McBain Andrew J.
Published: December 2018

Exposure to very low concentrations of biocides in the environment is a poorly understood risk factor for antimicrobial resistance. Repeated exposure to trace levels of the biocide benzalkonium chloride (BAC) resulted in loss of function (motility) and a general reduction in bacterial fitness but relatively minor decreases in susceptibility. These changes were accompanied by widespread changes in the
Escherichia coli
transcriptome. These results demonstrate the importance of including phenotypic characterization in studies designed to assess the risks of biocide exposure.
Diagnosis of Human Immunodeficiency Virus Infection
Authors: Parekh Bharat S. , Ou Chin-Yih , Fonjungo Peter N. , Kalou Mireille B. , Rottinghaus Erin , Puren Adrian , Alexander Heather , Hurlston Cox Mackenzie , Nkengasong John N.
Published: December 2018

HIV diagnostics have played a central role in the remarkable progress in identifying, staging, initiating, and monitoring infected individuals on life-saving antiretroviral therapy. They are also useful in surveillance and outbreak responses, allowing for assessment of disease burden and identification of vulnerable populations and transmission “hot spots,” thus enabling planning, appropriate interventions, and allocation of appropriate funding.
Cutaneous Mycobacterial Infections
Authors: Franco-Paredes Carlos , Marcos Luis A. , Henao-Martínez Andrés F. , Rodríguez-Morales Alfonso J. , Villamil-Gómez Wilmer E. , Gotuzzo Eduardo , Bonifaz Alexandro
Published: December 2018

Humans encounter mycobacterial species due to their ubiquity in different environmental niches. In many individuals, pathogenic mycobacterial species may breach our first-line barrier defenses of the innate immune system and modulate the activation of phagocytes to cause disease of the respiratory tract or the skin and soft tissues, sometimes resulting in disseminated infection.
Detecting cervical precancer and reaching underscreened women by using HPV testing on self samples: updated meta-analyses
Authors: Arbyn Marc , Smith Sara B , Temin Sarah , Sultana Farhana , Castle Philip
Published: December 2018

Objective

To evaluate the diagnostic accuracy of high-risk human papillomavirus (hrHPV) assays on self samples and the efficacy of self sampling strategies to reach underscreened women.

Design

Updated meta-analysis.

Data sources

Medline (PubMed), Embase, and CENTRAL from 1 January 2013 to 15 April 2018 (accuracy review), and 1 January 2014 to 15 April 2018 (participation review).

Review methods

Accuracy review: hrHPV assay on a vaginal self sample and a clinician sample; and verification of the presence of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) by colposcopy and biopsy in all enrolled women or in women with positive tests. Participation review: study population included women who were irregularly or never screened; women in the self sampling arm (intervention arm) were invited to collect a self sample for hrHPV testing; women in the control arm were invited or reminded to undergo a screening test on a clinician sample; participation in both arms was documented; and a population minimum of 400 women.

Results

56 accuracy studies and 25 participation trials were included. hrHPV assays based on polymerase chain reaction were as sensitive on self samples as on clinician samples to detect CIN2+ or CIN3+ (pooled ratio 0.99, 95% confidence interval 0.97 to 1.02). However, hrHPV assays based on signal amplification were less sensitive on self samples (pooled ratio 0.85, 95% confidence interval 0.80 to 0.89). The specificity to exclude CIN2+ was 2% or 4% lower on self samples than on clinician samples, for hrHPV assays based on polymerase chain reaction or signal amplification, respectively. Mailing self sample kits to the woman’s home address generated higher response rates to have a sample taken by a clinician than invitation or reminder letters (pooled relative participation in intention-to-treat-analysis of 2.33, 95% confidence interval 1.86 to 2.91). Opt-in strategies where women had to request a self sampling kit were generally not more effective than invitation letters (relative participation of 1.22, 95% confidence interval 0.93 to 1.61). Direct offer of self sampling devices to women in communities that were underscreened generated high participation rates (>75%). Substantial interstudy heterogeneity was noted (I2>95%).

Conclusions

When used with hrHPV assays based on polymerase chain reaction, testing on self samples was similarly accurate as on clinician samples. Offering self sampling kits generally is more effective in reaching underscreened women than sending invitations. However, since response rates are highly variable among settings, pilots should be set up before regional or national roll out of self sampling strategies.
Trends in socioeconomic inequalities in five major risk factors for cardiovascular disease in the Korean population: a cross-sectional study using data from the Korea National Health and Nutrition Examination Survey, 2001–2014
Authors: Kim Yoon Jung , Lee Ji Sung , Park Juri , Choi Dong Seop , Kim Doo Man , Lee Kee-Hyoung , Kim Ho Yeon , Kim Sin Gon , Lee Juneyoung
Published: December 2018

Objectives

To examine trends in socioeconomic inequalities in major cardiovascular disease (CVD) risk factors among the Korean population.

Design

Cross-sectional study.

Setting

A nationally representative population survey database.

Participants

A total of 42 725 Koreans, aged 25–64 years, who participated in the Korean National Health and Nutrition Examination Survey (KNHANES) II (2001) to VI (2013–2014).

Main outcome measures

Trends in socioeconomic inequalities in five major CVD risk factors (smoking, obesity, diabetes, hypertension and hypercholesterolaemia).

Results

Gender differences were noted in the time trends in socioeconomic inequalities in smoking, obesity, diabetes and hypertension. Among men, low socioeconomic status (SES) was associated with higher prevalence of smoking, but not with obesity, diabetes or hypertension. The magnitudes of socioeconomic inequalities in smoking, obesity and diabetes remained unchanged, and the magnitude of the inequality in hypertension decreased over time. However, among women, low SES was associated with higher prevalence of smoking, obesity, diabetes and hypertension. Time trends towards increasing socioeconomic inequalities, measured by income, in smoking, obesity and diabetes were found in women. Unlike the other CVD risk factors, hypercholesterolaemia was not associated with socioeconomic inequality.

Conclusions

SES had a stronger impact on major CVD risk factors among Korean women than men. Moreover, socioeconomic inequalities in smoking, obesity and diabetes worsened among Korean women over time. Public policies to prevent smoking, obesity and diabetes in women with lower SES are needed to address inequalities.
Understanding how and why audits work: protocol for a realist review of audit programmes to improve hospital care
Authors: Hut-Mossel Lisanne , Welker Gera , Ahaus Kees , Gans Rijk
Published: December 2018

Introduction

Many types of audits are commonly used in hospital care to promote quality improvements. However, the evidence on the effectiveness of audits is mixed. The objectives of this proposed realist review are (1) to understand how and why audits might, or might not, work in terms of delivering the intended outcome of improved quality of hospital care and (2) to examine under what circumstances audits could potentially be effective. This protocol will provide the rationale for using a realist review approach and outline the method.

Methods and analysis

This review will be conducted using an iterative four-stage approach. The first and second steps have already been executed. The first step was to develop an initial programme theory based on the literature that explains how audits are supposed to work. Second, a systematic literature search was conducted using relevant databases. Third, data will be extracted and coded for concepts relating to context, outcomes and their interrelatedness. Finally, the data will be synthesised in a five-step process: (1) organising the extracted data into evidence tables, (2) theming, (3) formulating chains of inference from the identified themes, (4) linking the chains of inference and formulating CMO configurations and (5) refining the initial programme theory. The reporting of the review will follow the ‘Realist and Meta-Review Evidence Synthesis: Evolving Standards’ (RAMESES) publication standards.

Ethics and dissemination

This review does not require formal ethical approval. A better understanding of how and why these audits work, and how context impacts their effectiveness, will inform stakeholders in deciding how to tailor and implement audits within their local context. We will use a range of dissemination strategies to ensure that findings from this realist review are broadly disseminated to academic and non-academic audiences.

PROSPERO registration number

CRD42016039882.
Understanding and evaluating new models of Child and Adolescent Mental Health Services in South-East England: a study protocol for an observational mixed-methods study
Authors: Rocks Stephen , Stepney Melissa , Glogowska Margaret , Fazel Mina , Tsiachristas Apostolos
Published: December 2018

Introduction

Increased demand for Child and Adolescent Mental Health Services (CAMHS), alongside concerns that services should be better commissioned to meet the needs of the most vulnerable, has contributed to a requirement to transform services to improve accessibility, quality of care and health outcomes. Following the submission of government-mandated transformation plans for CAMHS, services in England are changing in how, where and by whom they are delivered. This protocol describes the research methods to be applied to understand CAMHS transformations and evaluate the impact on the use of mental health services, patient care, satisfaction, health outcomes and health resource utilisation costs.

Methods and analysis

A mixed-methods approach will be taken in an observational retrospective study of CAMHS provided by a large National Health Service (NHS) mental health trust in South-East England (Oxford Health NHS Foundation Trust). Quantitative research will include descriptive analysis of routinely collected data, with difference-in-differences analysis supplemented with propensity score matching performed to assess the impact of CAMHS transformations from 2015 onwards. An economic evaluation will be conducted from a healthcare perspective to provide commissioners with indications of value for money. Qualitative research will include observations of services and interviews with key stakeholders including CAMHS staff, service users and guardians, to help identify mechanisms leading to changes in service delivery, as well as barriers and enabling factors in this phase of transformation.

Ethics and dissemination

This project has been registered with NHS Oxford Health Foundation Trust as a service evaluation. Informed consent will be sought from all stakeholders partaking in interviews according to good clinical practice. A local data sharing protocol will govern the transfer of quantitative data. Study findings will be published in professional journals for NHS managers and peer-reviewed scientific journals. They will be discussed in seminars targeting CAMHS providers, managers and commissioners and presented at scientific conferences.
Behind the wheel safety in palliative care: a literature review
Authors: Howard Mark , Ramsenthaler Christina
Published: December 2018

Background

Driving is a complex activity that requires physical abilities and adequate executive and cognitive functioning. There is concern among specialist palliative care services about patients continuing to drive despite having progressive incurable illnesses, comorbidities and medications to manage their symptoms.

Objectives

To determine the quality of literature available about driving that would apply to palliative care patients, specifically in relation to road test or simulated driving scores and neurocognitive testing.

Method

A literature search based on systematic principles was conducted on the Ovid Medline, PsycINFO, Embase and CINAHL database up to 14 October 2018. Patient populations with life-limiting illness such as cancer, cardiorespiratory and neurological diagnoses were included.

Results

37,546 articles were screened. 14 articles satisfied the search criteria. Six studies focused on patients with multiple sclerosis (MS). Four studies investigated driving ability in patients with Huntington’s disease. The remaining four articles studied heart failure, chronic obstructive pulmonary disease (COPD), interstitial lung disease and patients with cancer. In the road test studies, 19%–47% of patients with MS and Huntington’s failed the behind-the-wheel assessment. The simulated driving scores in seven studies demonstrated statistically significant differences in errors made between study participants and controls. Divided attention was found in seven studies to be associated with poorer road-test or simulated driving ability.

Conclusions

This review highlights the scarcity of studies available for patients who would be known to palliative care services. For most patient groups, a battery of neurocognitive tests combined with a road-test or simulated driving assessment is still considered the best practice in determining driving safety.
Increased IP-10 production by blood–nerve barrier in multifocal acquired demyelinating sensory and motor neuropathy and multifocal motor neuropathy
Authors: Shimizu Fumitaka , Oishi Mariko , Sawai Setsu , Beppu Minako , Misawa Sonoko , Matsui Naoko , Miyashiro Ai , Maeda Toshihiko , Takeshita Yukio , Nishihara Hideaki , Sano Yasuteru , Sato Ryota , Kaji Ryuji , Kuwabara Satoshi , Kanda Takashi
Published: December 2018

Objective

Dysfunction of the blood–nerve barrier (BNB) plays important roles in chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN). The aim of the present study was to identify the candidate cytokines/chemokines that cause the breakdown of the BNB using sera from patients with CIDP and MMN.

Methods

We determined the levels of 27 cytokines and chemokines in human peripheral nerve microvascular endothelial cells (PnMECs) after exposure to sera obtained from patients with CIDP variants (typical CIDP and multifocal acquired demyelinating sensory and motor neuropathy [MADSAM]), MMN and amyotrophic lateral sclerosis (ALS), and healthy controls (HC), using a multiplexed fluorescent bead-based immunoassay system.

Results

The induced protein (IP)10 level in the cells in both the MADSAM and MMN groups was markedly increased in comparison with the typical CIDP, ALS and HC groups. The other cytokines, including granulocyte colony-stimulating factor,vascular endothelial growth factor (VEGF) and interleukin-7, were also significantly upregulated in the MADSAM group. The increase of IP-10 produced by PnMECs was correlated with the presence of conduction block in both the MADSAM and MMN groups.

Conclusion

The autocrine secretion of IP-10 induced by patient sera in PnMECs was markedly upregulated in both the MADSAM and MMN groups. The overproduction of IP-10 by PnMECs leads to the focal breakdown of the BNB and may help to mediate the transfer of pathogenic T cells across the BNB, thereby resulting in the appearance of conduction block in electrophysiological studies of patients with MADSAM and MMN.
Abatacept in combination with methotrexate in Japanese biologic-naive patients with active rheumatoid arthritis: a randomised placebo-controlled phase IV study
Authors: Matsubara Tsukasa , Inoue Hiroshi , Nakajima Toshihiro , Tanimura Kazuhide , Sagawa Akira , Sato Yukio , Osano Kei , Nagano Shuji , Ueki Yukitaka , Hanyu Tadamasa , Hashizume Koichi , Amano Norihito , Tanaka Yoshiya , Takeuchi Tsutomu
Published: December 2018

Objectives

To evaluate efficacy and safety of abatacept+methotrexate (MTX) in biologic-naive, anticitrullinated protein antibody (ACPA)-positive Japanese patients with active rheumatoid arthritis (RA) and early erosion versus placebo+MTX.

Methods

In this phase IV, multicentre, double-blind study (NCT01758198), patients were randomised (1:1) to receive intravenous abatacept (~10 mg/kg) or placebo, plus MTX (≥6 mg/week). Primary efficacy objectives were to compare American College of Rheumatology 20 (ACR20) response rates at week 16 and mean change from baseline in van der Heijde-modified total Sharp score (vdH-mTSS) at week 24 between abatacept+MTX and placebo+MTX groups.

Results

Overall, 203 and 202 patients received abatacept+MTX and placebo+MTX, respectively. At week 16, ACR20 response rates were higher in the abatacept (75.4%) versus placebo group (27.7%; p<0.001). Mean change from baseline in vdH-mTSS at week 24 was 0.84 in the abatacept and 1.26 in the placebo group (p=0.017). Radiographic non-progression rates (change in vdH-mTSS≤smallest detectable change (1.9)) were 88.1% and 75.4% in abatacept and placebo groups, respectively. Adjusted mean change from baseline in Disease Activity Score 28 (C-reactive protein) (DAS28 (CRP)) at week 16 demonstrated a numerically greater reduction in the abatacept versus placebo group. Proportions of patients with DAS28 (CRP), Simplified Disease Activity Index and Clinical Disease Activity Index remission up to week 52 were higher in the abatacept versus placebo group. The abatacept safety profile was consistent with previous observations.

Conclusions

Compared with MTX alone, abatacept+MTX improved clinical symptoms and inhibited structural damage progression in ACPA-positive, Japanese patients with RA, early erosion and inadequate response to MTX.
William Derek Tavernor
Authors: Lees Peter , Noakes David , May Stephen , Sitford Colin
Published: December 2018

A man of action who gave the impression that he always knew where he was going.
Behavior of a hot mix asphalt made with recycled concrete aggregate and crumb rubber
Authors: Muniz de Farias Marcio , Quiñonez Sinisterra Ferney , Rondón Quintana Hugo Alexander
Published: December 2018

An experimental program was devised to evaluate the effect on the resistance of a hot mix asphalt, due to the total replacement of a natural aggregate (limestone — LS) by a recycled concrete aggregate (RCA). Two asphalt binders were used: conventional AC 50-70 (penetration grade) and AC 50-70 modified with crumb rubber (CRM). The mechanical properties investigated were the stability and flow ratio (Marshall test), indirect tensile strength, resistance to abrasion (Cantabro test), resilient modulus, resistance to permanent deformation, to fatigue and to moisture damage (modified Lottman test). When the LS is completely replaced by RCA, the resistance under monotonic loading, moisture damage and permanent deformation improved, the mass loss in the Cantabro test and the resilient modulus shows appropriate values, however, the fatigue resistance decreases. Besides, mixtures with RCA using CRM binder showed lower fatigue life under stress controlled tests, but much better rutting resistance.
Modified field equations from a complexified nonlocal metric
Authors: El-Nabulsi Rami Ahmad
Published: December 2018

We argue that it is possible to obtain higher-derivative Einstein’s field equations by means of an extended complexified backward–forward nonlocal extension of the space–time metric, which depends on space–time vectors. Our approach generalizes the notion of the covariant derivative along tangent vectors of a given manifold, and accordingly many of the differential geometrical operators and symbols used in general relativity. Equations of motion are derived and a nonlocal complexified general relativity theory is formulated. A number of illustrations are proposed and discussed accordingly.
Intra-articular injection of hydrogen sulfide decreased the progression of gonarthrosis
Authors: Aytekin Kürşad , Erhan Selma Şengiz , Erişgin Züleyha , Esenyel Cem Zeki , Takır Selçuk
Published: December 2018

Hydrogen sulfide (H2S) is found in both the plasma and synovial fluid of patients with gonarthrosis. In the present study, we investigated whether intra-articular injection of sodium hydrosulfide (NaSH) (1 mM, 30 μL), a H2S donor, might affect gonarthrosis in rats. Gonarthrosis was induced surgically in the left knees of rats and left for 6 weeks for the development of disease. Then, intra-articular injections of NaSH or methylprednisolone (1 mg/kg, 30 μL) were administered to rats. Half of each group was sacrificed at the end of the first day and the other half was sacrificed at the end of 4 weeks to evaluate early and later effects of injections on gonarthrosis. The injury induced by anterior cruciate ligament resection and medial meniscectomy in rats caused the development of gonarthrosis. As the duration lengthened after gonarthrosis induction, the progression of the disease continued. According to the modified Mankin Scoring System, intra-articular injection of NaSH histopathologically slowed the progression of gonarthrosis, whereas methylprednisolone was ineffective. In addition, NaSH decreased apoptosis in rat knees with gonarthrosis. Each treatment did not cause injury to healthy knees. Our results lead to the consideration that intra-articular NaSH administration may be effective in the progression of gonarthrosis.
Oriental Herbal Medicine for Neurological Disorders in Children: An Overview of Systematic Reviews
Authors: Lee Boram , Kwon Chan-Young , Chang Gyu Tae
Published: December 2018

Oriental herbal medicine (OHM) has been widely used in pediatric neurological disorders and has attracted attention as a safe and effective treatment. We aim to summarize and evaluate the evidence for OHM in pediatric neurological disorders for evidence-based decision-making. Without language restrictions, up-to-date research data were obtained from nine electronic databases. Systematic reviews (SRs) assessing the efficacy of OHM for pediatric neurological disorders were included. The methodological quality of each review was assessed using the AMSTAR instrument. The quality of evidence for the main findings was evaluated using the GRADE approach. Sixteen SRs comprising 169 randomized controlled trials with 19,542 participants were included. In epilepsy (six SRs, [Formula: see text]), OHM as an adjunctive or alternative therapy to antiepileptic drugs showed higher clinical symptom improvements than did antiepileptic drugs alone. The Activities of Daily Living scale score was significantly higher in children with cerebral palsy (one SR, [Formula: see text]) when OHM was added to rehabilitation. There were inconsistent results for tic disorder (four SRs, [Formula: see text]) and enuresis (two SRs, [Formula: see text]) and unclear results for attention deficit hyperactivity disorder (two SRs, [Formula: see text]) and autism spectrum disorder (one SR, [Formula: see text]). Eleven SRs reported adverse events, but no fatal adverse reaction was reported. The methodological quality of the included reviews was medium-to-high. The overall quality of evidence ranged from “very low” to “moderate.” In conclusion, the efficacy of OHM is promising for some pediatric neurological disorders such as epilepsy and cerebral palsy. However, more high-quality evidence is needed to make clinical recommendations on OHM use.
Prediction of Business Failure with Fuzzy Models
Authors: Terceño Antonio , Vigier Hernán , Scherger Valeria
Published: December 2018

This paper extends the theory of fuzzy diseases predictions in order to detect the causes of business failure. This extension is justified through the advantages of the reference model and its originality. Moreover, the fuzzy model is completed by this proposal and some parts of it have been published in isolated articles. For this purpose, the fuzzy theory is combined with the OWA operators to identify the factors that generate problems in firms. Also, a goodness index to validate its functionality and prediction capacity is introduced. The model estimates a matrix of economic- financial knowledge based on matrices of causes and symptoms. Knowing the symptoms makes it possible to estimate the causes, and managing them properly, allows monitoring and improving the company’s financial situation and forecasting its future. Also with this extension, the model can be useful to develop suitable computer systems for monitoring companies’ problems, warning of failures and facilitating decision-making.
Analysis of Long-Term Memory in the Mexican Exchange Market Using a Fuzzy Hurst Exponent: Does Intervention Matter?
Authors: Cortez Klender , Del Pilar Rodríguez Martha
Published: December 2018

The following article aims to detect if long-term memory exists in the Mexican exchange rate market. This research was conducted between 1992 and 2016, during which time different intervention mechanisms were presented. The interventions were divided as follows: a) crawling bands (01/1992–12/1994), b) free flotation in crisis (01/1995–07/1996), c) mixed operations with purchases and sales of dollars by the Central Bank (08/1996–06/2001), d) free flotation (07/2001–04/2003), e) accumulation of international reserves (05/2003–02/2009, f) mixed auctions (03/2009–02/2016), and g) free flotation with interest rate increases (03/2016–12/2016). To detect the presence of long-term memory in the peso–dollar exchange rates, we proposed a fuzzy Hurst exponent. The results evidenced distinct types of behaviors depending on the grade of intervention. Compared to a free-floating regime, persistence and fuzzy Hurst values decreased when the Central Bank intervened in the exchange market. On the other hand, uncertainty increased when monetary authorities imposed a mechanism for buying and selling dollars without an exchange rate target.
Brotli
Authors: Alakuijala Jyrki , Farruggia Andrea , Ferragina Paolo , Kliuchnikov Eugene , Obryk Robert , Szabadka Zoltan , Vandevenne Lode
Published: December 2018

Brotli is an open source general-purpose data compressor introduced by Google in late 2013 and now adopted in most known browsers and Web servers. It is publicly available on GitHub and its data format was submitted as RFC 7932 in July 2016. Brotli is based on the Lempel-Ziv compression scheme and planned as a generic replacement of Gzip and ZLib. The main goal in its design was to compress data on the Internet, which meant optimizing the resources used at decoding time, while achieving maximal compression density.

This article is intended to provide the first thorough, systematic description of the Brotli format as well as a detailed computational and experimental analysis of the main algorithmic blocks underlying the current encoder implementation, together with a comparison against compressors of different families constituting the state-of-the-art either in practice or in theory. This treatment will allow us to raise a set of new algorithmic and software engineering problems that deserve further attention from the scientific community.
Binary Sketches for Secondary Filtering
Authors: Mic Vladimir , Novak David , Zezula Pavel
Published: December 2018

This article addresses the problem of matching the most similar data objects to a given query object. We adopt a generic model of similarity that involves the domain of objects and metric distance functions only. We examine the case of a large dataset in a complex data space, which makes this problem inherently difficult. Many indexing and searching approaches have been proposed, but they have often failed to efficiently prune complex search spaces and access large portions of the dataset when evaluating queries. We propose an approach to enhancing the existing search techniques to significantly reduce the number of accessed data objects while preserving the quality of the search results. In particular, we extend each data object with its
sketch
, a short binary string in Hamming space. These sketches approximate the similarity relationships in the original search space, and we use them to filter out non-relevant objects not pruned by the original search technique. We provide a probabilistic model to tune the parameters of the sketch-based filtering separately for each query object. Experiments conducted with different similarity search techniques and real-life datasets demonstrate that the secondary filtering can speed-up similarity search several times.