bluuebunny/crossref_metadata_2025 huggingface dataset:
Study of the stability of tunnel construction based on double-heading advance construction method
Authors: Song Zhanping , Shi Guilin , Zhao Baoyun , Zhao Keming , Wang Junbao
Published: January 2020

The deformation and significant settlement of surrounding rock often occur during tunnel construction with the condition of abundant water and weak cementing sand. In order to study the construction method and stability under such soft stratum, this article takes Taoshuping tunnel as the engineering background and puts forward a new tunnel construction method—double-heading advance construction method by comparing the advantages and disadvantages of various traditional construction schemes. The numerical simulation of tunnel construction process using this method is carried out to illustrate the rationality and feasibility of the method. The conclusions are drawn by comparing the numerical simulation results with the field monitoring data analysis. The numerical simulation results show that the maximum settlement value caused by excavation construction is in the parts 5 and 6 of the upper half-section and the part 7 of the central section. The settlement values of parts 5, 6, and 7 accounted for 32.4%, 24.3%, and 18.9% of the total settlement values, respectively. So, the supporting measures for double-heading advance excavation construction of these three parts should be strengthened properly. The stress of the right hance changes greatly before and after the demolition of temporary support. The maximum positive value of stress is 23 kPa and the maximum negative value of stress is −32 kPa. Therefore, the length of temporary bracing should be strictly controlled during construction and the monitoring of the right hance area should be strengthened. Furthermore, it is necessary to strengthen the supporting measures and monitoring in the right spandrel area as the surrounding rock pressure in the right spandrel area is higher than the left spandrel area. The optimum excavation height of the upper half-section in Taoshuping tunnel is determined to be 5.4 m and the reasonable excavation distance between parts 1 and 5 is determined to be 25–30 m by parameter optimization. Finally, the variation law of numerical simulation and field monitoring results is consistent, which shows that the double-heading advance construction method has a better effect on the stability control of surrounding rock, and the rationality and feasibility of this method are validated effectively. Therefore, the double-heading advance method is suitable for tunnel construction in the sand stratum with rich water and weak cementation, and the successful implementation of this method in Taoshuping tunnel also provides a reference for subsequent tunnel construction in the sand stratum with rich water and weak cementation.
External force estimation of fracture reduction robot based on force residual method
Authors: Lei Jingtao , Zheng Gongliang , Hu Lei , Zhang Lihai , Wang Tianmiao
Published: January 2020

Robot-assisted fracture reduction surgery should be highly safe and accurate. It is necessary to accurately determine and control the reduction force of the reduction robot. In this article, a fracture reduction robot is designed with the configuration of the 6-universal-prismatic-universal (6-UPU). The vector method is used to analyze the kinematics of the reduction robot. The Jacobian matrix of the reduction robot and the second-order influence coefficient matrix of the acceleration are obtained. The Lagrangian method is adopted to analyze the dynamic of the reduction robot. The muscle contraction force of the femoral shaft fracture is analyzed based on the Hill model to determine the fracture reduction force. According to changing of the reduction force during the fracture reduction operation, a kind of external force estimation method based on force residual analysis is proposed. When there is no external force sensor at the end of the reduction robot, this method can be used to detect the reduction force in real time. According to the displacement, velocity, and output torque of each branch chain, the reduction force during the reduction operation of the reduction robot can be estimated. A simulation system is conducted and the simulation results show that the fracture reduction force can be estimated and accurately tracked in real time, which is of great significance for the safe operation of the fracture reduction robot.
Evidence for a dissociation between causal beliefs and instrumental actions
Authors: Pérez Omar D , Soto Fabian A
Published: January 2020

Human experiments have demonstrated that instrumental performance of an action and the causal beliefs of the effectiveness of an action in producing a reward are correlated and controlled by the probability of an action leading to a reward. The animal literature, however, shows that instrumental performance under free-operant training differs even when the reward probabilities are matched while subjects undergo training under ratio or interval schedules of reward. In two experiments, we investigated whether causal beliefs would correlate with instrumental performance under ratio and interval schedules for matched reward probabilities. In both experiments, we found that performance was higher under ratio than under interval training. However, causal beliefs were similar between these two conditions despite these differences in instrumental performance. When reward probabilities were increased by experimental manipulations in Experiment 2, the causal beliefs increased but performance decreased with respect to Experiment 1. This is evidence that instrumental performance and causal action-reward attribution may not follow from the same psychological process under free-operant training.
Revealing similarities in the perceptual span of young and older Chinese readers
Authors: Xie Fang , McGowan Victoria A , Chang Min , Li Lin , White Sarah J , Paterson Kevin B , Wang Jingxin , Warrington Kayleigh L
Published: January 2020

Older readers (aged 65+ years) of both alphabetic languages and character-based languages like Chinese read more slowly than their younger counterparts (aged 18–30 years). A possible explanation for this slowdown is that, due to age-related visual and cognitive declines, older readers have a smaller perceptual span and so acquire less information on each fixational pause. However, although aging effects on the perceptual span have been investigated for alphabetic languages, no such studies have been reported to date for character-based languages like Chinese. Accordingly, we investigated this issue in three experiments that used different gaze-contingent moving window paradigms to assess the perceptual span of young and older Chinese readers. In these experiments, text was shown either entirely as normal or normal only within a narrow region (window) comprising either the fixated word, the fixated word, and one word to its left, or the fixated word and either one or two words to its right. Characters outside these windows were replaced using a pattern mask (Experiment 1) or a visually similar character (Experiment 2), or blurred to render them unidentifiable (Experiment 3). Sentence reading times were overall longer for the older compared with the younger adults and differed systematically across display conditions. Crucially, however, the effects of display condition were essentially the same across the two age groups, indicating that the perceptual span for Chinese does not differ substantially for the older and young adults. We discuss these findings in relation to other evidence suggesting the perceptual span is preserved in older adulthood.
Fluidity in the perception of auditory speech: Cross-modal recalibration of voice gender and vowel identity by a talking face
Authors: Burgering Merel A , van Laarhoven Thijs , Baart Martijn , Vroomen Jean
Published: January 2020

Humans quickly adapt to variations in the speech signal. Adaptation may surface as recalibration, a learning effect driven by error-minimisation between a visual face and an ambiguous auditory speech signal, or as selective adaptation, a contrastive aftereffect driven by the acoustic clarity of the sound. Here, we examined whether these aftereffects occur for vowel identity and voice gender. Participants were exposed to male, female, or androgynous tokens of speakers pronouncing /e/, /ø/, (embedded in words with a consonant-vowel-consonant structure), or an ambiguous vowel halfway between /e/ and /ø/ dubbed onto the video of a male or female speaker pronouncing /e/ or /ø/. For both voice gender and vowel identity, we found assimilative aftereffects after exposure to auditory ambiguous adapter sounds, and contrastive aftereffects after exposure to auditory clear adapter sounds. This demonstrates that similar principles for adaptation in these dimensions are at play.
Recovery self-regulation in sport: Theory, research, and practice
Authors: Balk Yannick A , Englert Chris
Published: January 2020

A large body of research has shown that self-regulation is an important aspect underlying athletes’ well-being and performance. However, self-regulation skills are equally important for post-performance situations, particularly with regard to the recovery process. This review highlights relevant self-regulation skills and provides a brief overview of theories, research findings, and practical recommendations regarding self-regulation and recovery in sport and exercise. Recovery self-regulation is defined as the act of identifying one's current state, one's desired future state and undertaking actions to minimize the discrepancy between both states during the recovery phase (e.g., between training sessions or competitions). Several self-regulation skills relevant to this process are discussed in the current review. First, self-monitoring is a central self-regulatory skill for successfully regulating post-performance states. Second, there is an important role for the regulation of cognition and emotion as complete recovery is only accomplished when both physical and mental resources are replenished. Specifically, detachment and mental rest (i.e., ceasing cognitive effort) enable athletes to restore depleted resources. Finally, self-control is often required to initiate appropriate, and sometimes effortful, recovery activities. That is, athletes may have to exert self-control to undertake activities, particularly when they are tired, stressed, or in a negative mood. Developing recovery self-regulation skills will likely benefit athletes’ physical and mental recovery from training and competition, which can have positive effects on long-term health, well-being, and performance.
Managing patients in care homes
Authors: Gill Michael
Published: January 2020

Older people in care homes deserve the best health and social care we can offer. Their care needs are usually high and they are vulnerable either physically, cognitively or both. They are likely to have several long-term conditions and be in the last year or so of life. Although some may have families and friends supporting them with regular visits and advocacy, others may be more alone and socially isolated. Care homes are traditionally classed as either residential homes or nursing homes, with some being dual registered. The main difference is the presence of 24-hour on-site qualified nursing support in nursing homes. This means that, in general, the residents of nursing homes are more dependent and complex. This article will first describe how to approach the planning and delivery of primary care services to nursing homes, and then consider some of the most common problems and conditions. Much of this also applies to residential home residents.
Is venous thromboembolism prophylaxis beneficial in upper limb major joint replacement surgery? A systematic review
Authors: Kadhum Murtaza , Elniel Abdel Rahim , Furniss Dominic
Published: January 2020

Background

Upper limb arthroplasty is an increasingly used treatment modality for end-stage joint disease of the shoulder, elbow and wrist. Whilst complications have been reported, the risk of venous thromboembolism has received less attention when compared to the lower limb. Guidance to aid clinical decision-making remains limited. This review aims to ascertain whether venous thromboembolism prophylaxis is beneficial after upper limb major joint replacement surgery.

Methods

A systematic review was performed in April 2019, utilising EMBASE, MEDLINE, Cochrane and Google Scholar. All clinical studies reporting venous thromboembolism incidence and risk reduction (after prophylaxis) in upper limb joint replacement were included.

Results

Twenty-four observational studies were identified. The reported incidence of venous thromboembolism ranged from 0.2% to 16% (weighted mean 0.68%) and 0.2% to 0.8% (weighted mean 0.49%) in shoulder and elbow arthroplasty, respectively. No records for wrist arthroplasty were found. In the literature, baseline venous thromboembolism risk of patients without an operation is reported as 0.5%.

Discussion

There is a lack of good quality evidence regarding the risks and benefits of venous thromboembolism prophylaxis in upper limb major joint replacement surgery. We recommend further research, ideally formal randomised controlled trials to guide recommendations. Although venous thromboembolism is rare in upper limb surgery, surgeons should remain vigilant to this possibility.
Dihydrochalcone Glycosides From Balanophora harlandii
Authors: Prakash Indra , Qian Yong , Wang Bin , Xin Zhenqiang , Ma Gil , Yang Zhou , Higiro Juvenal , Petrovic Goran B. , Tian Wenshuai , Xie Tianpei
Published: January 2020

Dihydrochalcone class of compounds displays good performance in taste modulation on several natural non-caloric/low-caloric sweeteners. Compounds such as hesperetin dihydrochalcone (HDC) and hesperetin dihydrochalcone-4′- O-β-d-glucoside (HDCG) were reported to be found in nature. However, the evidence was not complete to support their natural presence. The Coca-Cola Company has been working on the identification of natural sources of reported dihydrochalcones, as well as the exploration of new natural dihydrochalcones. During the investigation on plant Balanophora harlandii, the natural presence of HDCG was confirmed, and 3 new analogs have been identified. In this paper, detailed structural elucidation of known HDCG and 3 new analogs have been described.
Pouchitis: Treatment dilemmas at different stages of the disease
Authors: Barreiro‐de Acosta Manuel , Bastón‐Rey Iria , Calviño‐Suárez Cristina , Enrique Domínguez‐Muñoz J
Published: January 2020

Pouchitis is a frequent complication in ulcerative colitis patients after proctocolectomy with ileal pouch–anal anastomosis. It is an unspecific inflammation of the pouch with unknown aetiology. First‐line treatment for acute and chronic pouchitis is antibiotics. Some cases of severe chronic refractory pouchitis may benefit from biological treatment. Anti‐tumour necrosis factor should be recommended as the first option, leaving the new biologicals for multirefractory patients. Permanent ileostomy may be an option in severe cases, after failure of medical treatment. Prophylaxis therapy with a probiotic mixture is recommended after the first episode of pouchitis, whereas it is not clear whether probiotics are useful for all patients after surgery. Here, we present a case report and review the treatment options in different forms of pouchitis.
The logistical management of tertiary urethral disease in the United Kingdom: Implications from an online audit of male reconstructive urethral surgery
Authors: Payne Stephen R , Fowler Sarah , Mundy Anthony R , Alhasso A. , Almallah Y. , Anderson P. , Andrich D. , Baird A. , Biers S. , Browning A. , Chapple C. , Cherian J. , Clarke L. , Conn I. , Dickerson D. , Doble A. , Dorkin T. , Duggan B. , Eardley I. , Garaffa G. , Greenwell T. , Hadway P. , Harding C. , Hilmy M. , Inman R. , Kayes O. , Kirchin V. , Krishnan R. , Kumar V. , Lemberger J. , Malone P. , Moore J. , Moore K. , Mundy A. , Noble J. , Nurse D. , Palmer M. , Payne S. , Pickard R. , Rai J. , Rees R. , Roux J. , Seipp C. , Shabbir M. , Saxby M. , Sharma D. , Sinclair A. , Summerton D. , Tatarov O. , Thiruchelvam N. , Venn S , Watkin N. , Zacherakis E.
Published: January 2020

Objective:

To determine those patient groupings, based on volume and risk, whose optimal urethral reconstructive management might be provided by a reorganisation of UK reconstructive surgeons.

Methods:

Between 2010 and 2017, ~689 men/year were enrolled onto an online audit platform collecting data about urethral reconstruction in the UK; this accrual was compared against hospital episode statistics (HES). The available workforce, and where this was based, was collected. Individual and institutional incumbent patient volumes, pathology, surgical complexity and outcomes from treatment were collated to stratify volume/risk groups.

Results:

More than 90% of all HES-recorded data were accrued, being provided by 50 surgeons at 39 operative sites. Most reconstructive surgery was provided at 10 centres performing >20 procedures/year. More than 50% of all interventions were of a high-volume low-risk type. Of activity, 32.3% was intermediate volume or moderate risk, and 12.5% of men presented for lower-volume or higher-risk procedures.

Conclusion:

Correlation of detailed volume/outcome data allows the definition of patient populations presenting for urethral reconstruction. Stratification of each group’s management, to optimise the surgical outcome, may be applied to a hierarchical service delivery model based on the complexity of the patient’s presenting urethral pathology.

Level of evidence:

Level IV
Does routine histology alter management post circumcision?
Authors: Kerr Lynne , Hendry Jane , Crookshanks Aaron , Taylor Joby
Published: January 2020

Objective:

Circumcision is a commonly performed urological procedure, histology is often requested with unexpected malignancy cited as the reason. This paper aims to determine if routine histology following circumcision alters the clinical management of patients.

Patients and methods:

The clinical records of 508 consecutive adult patients circumcised at a district general hospital between 1/1/12 and 31/12/16 were retrospectively reviewed. Two groups were available for comparison, those with histological diagnosis (359 patients) and those with a clinical diagnosis only (149 patients). The following data were collected: indication for circumcision; preoperative clinical and histological diagnosis; patient follow-up (mean 40 months).

Results:

A total of 508 patients were reviewed. Histology was requested for 359 specimens (70.7%). Six cases of squamous cell carcinoma were correctly identified clinically and there were no cases of unexpected malignancy. The clinical diagnosis of lichen sclerosus was correct in 92% of cases; 39 patients were re-referred following discharge, only one required further management of a urethral stricture.

Conclusion:

The results of our study show there is no difference in the outcomes or re-referral rates of patients who have routine histology requested following circumcision compared with those who do not. Clinical diagnosis is consistently accurate. There is a minimal number of patients referred back to the service, even with lichen sclerosus, and histology does not affect the rate of this. We conclude that routine histology does not alter patient management following circumcision and is not required unless a clinical suspicion of malignancy exists. This study represents the largest cohort of circumcision patients and includes the longest period of follow-up to add to the current body of literature.

Levels of evidence:

2b retrospective consecutive cohort study with follow up.
The Symptom Checklist: Frequency and Severity Scale – translation and psychometric properties of the Swedish version
Authors: Carnlöf Carina , Malinowsky Camilla , Insulander Per , Gadler Fredrik , Jensen-Urstad Mats , Iwarzon Marie
Published: January 2020

The Symptom Checklist: Frequency and Severity Scale (SCL) is a symptom-specific questionnaire that measures the patient’s perception of the frequency and severity of arrhythmia-related symptoms. Worldwide, the SCL is one of the most used symptom-specific questionnaires for this purpose. Until now, there has not been a valid Swedish translation of the SCL. This study aimed to translate the SCL into Swedish and test the face, content and construct validity of the translated version. The questionnaire was translated using the WHO’s recommendations for translation. Using the ‘think aloud method’, we gathered data from 12 patients regarding the intelligibility of the questions. Using exploratory factor analysis (EFA), we evaluated the face validity, construct validity and internal consistency properties of the questionnaire. The study included 646 patients with different types of supraventricular tachycardia, atrial fibrillation (AF) atrial flutter (AFL), atrioventricular reentrant tachycardia (AVRT), atrioventricular nodal reentrant tachycardia (AVNRT), and ectopic atrial tachycardia (EAT). Translation and face validity were found to be acceptable. Construct validity evaluated using EFA and principal component analysis with varimax rotation identified four factors with eigenvalues greater than 1 and factor loading equal to or greater than 0.364, accounting for 58% and 53% of the variance in the frequency scale and the severity scale, respectively. Reliability evaluation revealed high internal consistency. For both the frequency and severity scale, the Cronbach’s alpha coefficient was 0.88. Our results show evidence that the Swedish version of the SCL has good psychometric properties according to face and construct validity and internal consistency for patients with AF, AFL, AVRT, AVNRT and EAT, and is reproducible and valid.
Shadow Education in Europe: Growing Prevalence, Underlying Forces, and Policy Implications
Authors: Bray Mark
Published: January 2020

Purpose:

Private supplementary tutoring, widely known as shadow education, has long been visible in East Asia, and now has spread to other parts of the world including Europe. This article maps the phenomenon, showing variations within Europe and analyzing its growth, underlying forces, and policy implications.

Design/Approach/Methods:

The article assembles a regional picture from available national sources. It focuses on the 28 members of the European Union.

Findings:

Within Europe, four subregions may be identified. Most prominent for the longest duration has been Southern Europe, pushed by political forces and cultural factors. In Eastern Europe, shadow education became prominent following the collapse of the Soviet Union and accompanying economic and social structures during which teachers and others had to earn extra incomes. In Western Europe, the advent of marketization alongside government schooling has fueled the growth of shadow education. Only in Northern Europe does shadow education remain modest in scale, but it is growing there too.

Originality/Value:

The article identifies forces underlying the growth of shadow education in Europe and highlights policy implications. By contributing this regional perspective to the wider literature on shadow education, the article permits juxtaposition with patterns in East Asia and elsewhere.
How Cooperation Reinforces Conflict Over Time
Authors: Schweiger Sylvia , Konlechner Stefan W. , Güttel Wolfgang H.
Published: January 2020

Managing projects raises multiple tensions such as the need to balance cooperativeness and assertiveness. By adopting a process perspective, we analyze why a project group consisting of three heterogeneous subgroups is failing to uphold such balance over time. Instead, overemphasizing cooperativeness in the early phases of the project led to over-assertiveness and escalation of group conflict. We identify three mechanisms for reinforcing dynamics. First, we find that subgroups overestimate other subgroups’ behavioral autonomy, which promotes holding simplified, negative images of each other. Second, subgroups adopt vertical disidentification when they define their own particular role. Third, cooperativeness conceals pejorative perceptions.
Project Is as Project Does
Authors: Salovaara Perttu , Savolainen Jussi , Ropo Arja
Published: January 2020

The purpose of the article is to further develop the processual approach in project management theorizing. The article introduces Gadamer’s (2004) play ontology as a novel perspective used to describe microactivities in a project environment. Play ontology refers to the back-and-forth movements of seemingly mundane microactivities as they unfold during a project. The findings of the study suggest that sensitivity to the microactivities allows considering dissonant or indecisive events as vital and constructive project elements. Play ontology offers new ways for conceptualizing a project as a process: as something that emerges through practical activities as a dynamic and complex phenomenon.
An update on the molecular pathogenesis and potential therapeutic targeting of AML with t(8;21)(q22;q22.1);RUNX1-RUNX1T1
Authors: Al-Harbi Sayer , Aljurf Mahmoud , Mohty Mohamad , Almohareb Fahad , Ahmed Syed Osman Ali
Published: January 2020

Acute myeloid leukemia (AML) with t(8;21)(q22;q22.1);RUNX1-RUNX1T1, one of the core-binding factor leukemias, is one of the most common subtypes of AML with recurrent genetic abnormalities and is associated with a favorable outcome. The translocation leads to the formation of a pathological RUNX1-RUNX1T1 fusion that leads to the disruption of the normal function of the core-binding factor, namely, its role in hematopoietic differentiation and maturation. The consequences of this alteration include the recruitment of repressors of transcription, thus blocking the expression of genes involved in hematopoiesis, and impaired apoptosis. A number of concurrent and cooperating mutations clearly play a role in modulating the proliferative potential of cells, including mutations in KIT, FLT3, and possibly JAK2. RUNX1-RUNX1T1 also appears to interact with microRNAs during leukemogenesis. Epigenetic factors also play a role, especially with the recruitment of histone deacetylases. A better understanding of the concurrent mutations, activated pathways, and epigenetic modulation of the cellular processes paves the way for exploring a number of approaches to achieve cure. Potential approaches include the development of small molecules targeting the RUNX1-RUNX1T1 protein, the use of tyrosine kinase inhibitors such as dasatinib and FLT3 inhibitors to target mutations that lead to a proliferative advantage of the leukemic cells, and experimentation with epigenetic therapies. In this review, we unravel some of the recently described molecular pathways and explore potential therapeutic strategies.
Supramaximal calcium signaling triggers procoagulant platelet formation
Authors: Abbasian Nima , Millington-Burgess Sarah L. , Chabra Shirom , Malcor Jean-Daniel , Harper Matthew T.
Published: January 2020

Procoagulant platelets promote thrombin generation during thrombosis. Platelets become procoagulant in an all-or-nothing manner. We investigated how distinct Ca2+ signaling between platelet subpopulations commits some platelets to become procoagulant, using the high-affinity Ca2+ indicator Fluo-4, which may become saturated during platelet stimulation, or low-affinity Fluo-5N, which reports only very high cytosolic Ca2+ concentrations. All activated platelets had high Fluo-4 fluorescence. However, in Fluo-5N–loaded platelets, only the procoagulant platelets had high fluorescence, indicating very high cytosolic Ca2+. This finding indicates a novel, “supramaximal” Ca2+ signal in procoagulant platelets (ie, much higher than normally considered maximal). Supramaximal Ca2+ signaling and the percentage of procoagulant platelets were inhibited by cyclosporin A, a mitochondrial permeability transition pore blocker, and Ru360, an inhibitor of the mitochondrial Ca2+ uniporter, with no effect on Fluo-4 fluorescence. In contrast, Synta-66, an Orai1 blocker, reduced Fluo-4 fluorescence but did not directly inhibit generation of the supramaximal Ca2+ signal. Our findings show a distinct pattern of Ca2+ signaling in procoagulant platelets and provide a new framework to interpret the role of platelet signaling pathways in procoagulant platelets. This requires reassessment of the role of different Ca2+ channels and may provide new targets to prevent formation of procoagulant platelets and limit thrombosis.
Robust CD4+ T-cell recovery in adults transplanted with cord blood and no antithymocyte globulin
Authors: Politikos Ioannis , Lavery Jessica A. , Hilden Patrick , Cho Christina , Borrill Taylor , Maloy Molly A. , Giralt Sergio A. , van den Brink Marcel R. M. , Perales Miguel-Angel , Barker Juliet N.
Published: January 2020

Quality of immune reconstitution after cord blood transplantation (CBT) without antithymocyte globulin (ATG) in adults is not established. We analyzed immune recovery in 106 engrafted adult CBT recipients (median age 50 years [range 22-70]) transplanted for hematologic malignancies with cyclosporine/mycophenolate mofetil immunoprophylaxis and no ATG. Patients were treated predominantly for acute leukemia (66%), and almost all (96%) underwent myeloablation. Recovery of CD4+ T cells was faster than CD8+ T cells with median CD4+ T-cell counts exceeding 200/mm3 at 4 months. Early post-CBT, effector memory (EM), and central memory cells were the most common CD4+ subsets, whereas effector and EM were the most common CD8+ T-cell subsets. Naive T-cell subsets increased gradually after 6 to 9 months post-CBT. A higher engrafting CB unit infused viable CD3+ cell dose was associated with improved CD4+ and CD4+CD45RA+ T-cell recovery. Cytomegalovirus reactivation by day 60 was associated with an expansion of total, EM, and effector CD8+ T cells, but lower CD4+ T-cell counts. Acute graft-versus-host disease (aGVHD) did not significantly compromise T-cell reconstitution. In serial landmark analyses, higher CD4+ T-cell counts and phytohemagglutinin responses were associated with reduced overall mortality. In contrast, CD8+ T-cell counts were not significant. Recovery of natural killer and B cells was prompt, reaching medians of 252/mm3 and 150/mm3 by 4 months, respectively, although B-cell recovery was delayed by aGVHD. Neither subset was significantly associated with mortality. ATG-free adult CBT is associated with robust thymus-independent CD4+ T-cell recovery, and CD4+ recovery reduced mortality risk.
Microglia P2X4R-BDNF signalling contributes to central sensitization in a recurrent nitroglycerin-induced chronic migraine model
Authors: Long Ting , He Wei , Pan Qi , Zhang Shanshan , Zhang Dunke , Qin Guangcheng , Chen Lixue , Zhou Jiying
Published: January 2020

Background

According to our previous study, microglia P2X4 receptors (P2X4Rs) play a pivotal role in the central sensitization of chronic migraine (CM). However, the molecular mechanism that underlies the crosstalk between microglia P2X4Rs and neurons of the trigeminal nucleus caudalis (TNC) is not fully understood. Therefore, the aim of this study is to examine the exact P2X4Rs signalling pathway in the development of central sensitization in a CM animal model.

Methods

We used an animal model with recurrent intermittent administration of nitroglycerin (NTG), which closely mimics CM. NTG-induced basal mechanical and thermal hypersensitivity were evaluated using a von Frey filament test and an increasing-temperature hot plate apparatus (IITC). We detected P2X4Rs, brain-derived neurotrophic factor (BDNF) and phosphorylated p38 mitogen-activated protein kinase (p-p38-MAPK) expression profiles in the TNC. We investigated the effects of a P2X4R inhibitor (5-BDBD) and an agonist (IVM) on NTG-induced hyperalgesia and neurochemical changes as well as on the expression of p-p38-MAPK and BDNF. We also detected the effects of a tropomyosin-related kinase B (TrkB) inhibitor (ANA-12) on the CM animal model in vivo. Then, we evaluated the effect of 5-BDBD and SB203580 (a p38-MAPK inhibitors) on the release and synthesis of BDNF in BV2 microglia cells treated with 50 μM adenosine triphosphate (ATP).

Results

Chronic intermittent administration of NTG resulted in chronic mechanical and thermal hyperalgesia, accompanied by the upregulation of P2X4Rs and BDNF expression. 5-BDBD or ANA-12 prevented hyperalgesia induced by NTG, which was associated with a significant inhibition of the NTG-induced increase in phosphorylated extracellular regulated protein kinases (p-ERK) and calcitonin gene related peptide (CGRP) release in the TNC. Repeated administration of IVM produced sustained hyperalgesia and significantly increased the levels of p-ERK and CGRP release in the TNC. Activating P2X4Rs with ATP triggered BDNF release and increased BDNF synthesis in BV2 microglia, and these results were then reduced by 5-BDBD or SB203580.

Conclusions

Our results indicated that the P2X4R contributes to the central sensitization of CM by releasing BDNF and promoting TNC neuronal hyper-excitability. Blocking microglia P2X4R-BDNF signalling may have an effect on the prevention of migraine chronification.
Forecasts of future scenarios for airport noise based on collection and processing of web data
Authors: Pretto Marco , Giannattasio Pietro , De Gennaro Michele , Zanon Alessandro , Kuehnelt Helmut
Published: January 2020

Purpose

This paper presents an analysis of short-term (2025) scenarios for noise emission from civil air traffic in airport areas.

Methods

Flight movements and noise levels at a given airport are predicted using a web-data-informed methodology based on the ECAC Doc.29 model. This methodology, developed by the authors in a previous work, relies on the collection and processing of air traffic web data to reconstruct flight events to be fed into the ECAC model. Three new elements have been included: i) topographic information from digital elevation models, ii) a fleet substitution algorithm to estimate the impact of newer aircraft, and iii) a generator of flight events to simulate the expected traffic increase.

Results

The effects of these elements are observed in 2025 scenarios for the airports of London Heathrow, Frankfurt and Vienna-Schwechat. The results quantify the noise reduction from new aircraft and its increment due to the air traffic growth forecast by EUROCONTROL.
A pipeline to create predictive functional networks: application to the tumor progression of hepatocellular carcinoma
Authors: Folschette Maxime , Legagneux Vincent , Poret Arnaud , Chebouba Lokmane , Guziolowski Carito , Théret Nathalie
Published: January 2020

Background

Integrating genome-wide gene expression patient profiles with regulatory knowledge is a challenging task because of the inherent heterogeneity, noise and incompleteness of biological data. From the computational side, several solvers for logic programs are able to perform extremely well in decision problems for combinatorial search domains. The challenge then is how to process the biological knowledge in order to feed these solvers to gain insights in a biological study. It requires formalizing the biological knowledge to give a precise interpretation of this information; currently, very few pathway databases offer this possibility.

Results

The presented work proposes an automatic pipeline to extract automatically regulatory knowledge from pathway databases and generate novel computational predictions related to the state of expression or activity of biological molecules. We applied it in the context of hepatocellular carcinoma (HCC) progression, and evaluate the precision and the stability of these computational predictions. Our working base is a graph of 3383 nodes and 13,771 edges extracted from the KEGG database, in which we integrate 209 differentially expressed genes between low and high aggressive HCC across 294 patients. Our computational model predicts the shifts of expression of 146 initially non-observed biological components. Our predictions were validated at 88% using a larger experimental dataset and cross-validation techniques. In particular, we focus on the protein complexes predictions and show for the first time that NFKB1/BCL-3 complexes are activated in aggressive HCC. In spite of the large dimension of the reconstructed models, our analyses over the computational predictions discover a well constrained region where KEGG regulatory knowledge constrains gene expression of several biomolecules. These regions can offer interesting windows to perturb experimentally such complex systems.

Conclusion

This new pipeline allows biologists to develop their own predictive models based on a list of genes. It facilitates the identification of new regulatory biomolecules using knowledge graphs and predictive computational methods. Our workflow is implemented in an automatic python pipeline which is publicly available at https://github.com/LokmaneChebouba/key-pipeand contains as testing data all the data used in this paper.
Robust estimation of heritability and predictive accuracy in plant breeding: evaluation using simulation and empirical data
Authors: Lourenço Vanda Milheiro , Ogutu Joseph Ochieng , Piepho Hans-Peter
Published: January 2020

Background

Genomic prediction (GP) is used in animal and plant breeding to help identify the best genotypes for selection. One of the most important measures of the effectiveness and reliability of GP in plant breeding is predictive accuracy. An accurate estimate of this measure is thus central to GP. Moreover, regression models are the models of choice for analyzing field trial data in plant breeding. However, models that use the classical likelihood typically perform poorly, often resulting in biased parameter estimates, when their underlying assumptions are violated. This typically happens when data are contaminated with outliers. These biases often translate into inaccurate estimates of heritability and predictive accuracy, compromising the performance of GP. Since phenotypic data are susceptible to contamination, improving the methods for estimating heritability and predictive accuracy can enhance the performance of GP. Robust statistical methods provide an intuitively appealing and a theoretically well justified framework for overcoming some of the drawbacks of classical regression, most notably the departure from the normality assumption. We compare the performance of robust and classical approaches to two recently published methods for estimating heritability and predictive accuracy of GP using simulation of several plausible scenarios of random and block data contamination with outliers and commercial maize and rye breeding datasets.

Results

The robust approach generally performed as good as or better than the classical approach in phenotypic data analysis and in estimating the predictive accuracy of heritability and genomic prediction under both the random and block contamination scenarios. Notably, it consistently outperformed the classical approach under the random contamination scenario. Analyses of the empirical maize and rye datasets further reinforce the stability and reliability of the robust approach in the presence of outliers or missing data.

Conclusions

The proposed robust approach enhances the predictive accuracy of heritability and genomic prediction by minimizing the deleterious effects of outliers for a broad range of simulation scenarios and empirical breeding datasets. Accordingly, plant breeders should seriously consider regularly using the robust alongside the classical approach and increasing the number of replicates to three or more, to further enhance the accuracy of the robust approach.
A modified Delphi study to identify the features of high quality measurement plans for healthcare improvement projects
Authors: Woodcock Thomas , Adeleke Yewande , Goeschel Christine , Pronovost Peter , Dixon-Woods Mary
Published: January 2020

Background

The design and execution of measurement in quality improvement (QI) initiatives is often poor. Better guidance on “what good looks like” might help to mitigate some of the problems. We report a consensus-building process that sought to identify which features are important to include in QI measurement plans.

Methods

We conducted a three-stage consensus-building approach: (1) identifying the list of features of measurement plans that were potential candidates for inclusion based on literature review and the study team’s experience; (2) a two-round modified Delphi exercise with a panel of experts to establish consensus on the importance of these features; and (3) a small in-person consensus group meeting to finalise the list of features.

Results

A list of 104 candidate questions was generated. A panel of 19 experts in the Delphi reviewed these questions and produced consensus on retaining 46 questions in the first round and on a further 22 in the second round. Thematic analysis of open text responses from the panellists suggested a number of areas of debate that were explicitly considered by the consensus group. The exercise yielded 74 questions (71% of 104) on which there was consensus in five categories of measurement relating to: design, data collection and management, analysis, action, and embedding.

Conclusions

This study offers a consensus-based view on the features of a good measurement plan for a QI project in healthcare. The results may be of use to QI teams, funders and evaluators, but are likely to require further development and testing to ensure feasibility and usefulness.
A computational method to quantitatively measure pediatric drug safety using electronic medical records
Authors: Yu Gang , Zeng Xian , Ni Shaoqing , Jia Zheng , Chen Weihong , Lu Xudong , An Jiye , Duan Huilong , Shu Qiang , Li Haomin
Published: January 2020

Background

Drug safety in children is a major concern; however, there is still a lack of methods for quantitatively measuring, let alone to improving, drug safety in children under different clinical conditions. To assess pediatric drug safety under different clinical conditions, a computational method based on Electronic Medical Record (EMR) datasets was proposed.

Methods

In this study, a computational method was designed to extract the significant drug-diagnosis associations (based on a Bonferroni-adjusted hypergeometric P-value < 0.05) among drug and diagnosis co-occurrence in EMR datasets. This allows for differences between pediatric and adult drug use to be compared based on different EMR datasets. The drug-diagnosis associations were further used to generate drug clusters under specific clinical conditions using unsupervised clustering. A 5-layer quantitative pediatric drug safety level was proposed based on the drug safety statement of the pediatric labeling of each drug. Therefore, the drug safety levels under different pediatric clinical conditions were calculated. Two EMR datasets from a 1900-bed children’s hospital and a 2000-bed general hospital were used to test this method.

Results

The comparison between the children’s hospital and the general hospital showed unique features of pediatric drug use and identified the drug treatment gap between children and adults. In total, 591 drugs were used in the children’s hospital; 18 drug clusters that were associated with certain clinical conditions were generated based on our method; and the quantitative drug safety levels of each drug cluster (under different clinical conditions) were calculated, analyzed, and visualized.

Conclusion

With this method, quantitative drug safety levels under certain clinical conditions in pediatric patients can be evaluated and compared. If there are longitudinal data, improvements can also be measured. This method has the potential to be used in many population-level, health data-based drug safety studies.
Prevention of post-splenectomy sepsis in patients with asplenia - a study protocol of a controlled trial
Authors: Bayrhuber Marianne , Anka Natascha , Camp Johannes , Glattacker Manuela , Farin Erik , Rieg Siegbert
Published: January 2020

Background

Patients with asplenia have a significantly increased lifelong risk of severe invasive infections, particular post-splenectomy sepsis (PSS). Clear preventive measures have been described in the literature, but previous studies found poor implementation of prevention recommendations. Aim of the study is to improve the adherence to guideline-based preventive measures and thereby reduce the incidence of PSS by a novel telephone-delivered intervention that involves both patients and their physicians.

Methods

A prospective controlled, two-armed historical control group design is used to evaluate the new intervention compared to usual care. The intervention for patients includes both educational aspects and, building on the Health Action Process Approach (HAPA), intervention components that promote motivation and planning of preventive measures. For physicians the intervention is primarily information-based. The primary outcome, the adherence to preventative measures, is indicated by a study-specific ‘Preventing PSS-score’ (PrePSS-score), which is assessed at baseline and at 6-months follow-up. Secondary outcomes include, amongst others, patient self-efficacy and action-planning, asplenia-specific health literacy, general self-management and asplenia-specific self-management. In a process-evaluating part of the study interview-data on patients’ and physicians’ evaluation of the intervention will be gathered.

Discussion

This trial will provide evidence about the effectiveness of the novel prevention intervention for asplenic patients. If demonstrated beneficial, the intervention manual will be made publicly available to enable implementation in practice. The experience gained within this trial may also be valuable for prevention strategies in patients with other diseases.

Trial registration

German Clinical Trials Register (DRKS): DRKS00015238; Trial registration date 07. December 2018.
Does phone messaging improves tuberculosis treatment success? A systematic review and meta-analysis
Authors: Gashu Kassahun Dessie , Gelaye Kassahun Alemu , Mekonnen Zeleke Abebaw , Lester Richard , Tilahun Binyam
Published: January 2020

Background

Compliance to anti-TB treatment is crucial in achieving cure and avoiding the emergence of drug resistance. Electronic health (eHealth) interventions are included in the strategy to end the global Tuberculosis (TB) epidemic by 2035. Evidences showed that mobile messaging systems could improve patient adherence to clinic appointment for diagnosis and treatment. This review aimed to assess the effect of mobile-phone messaging on anti-TB treatment success.

Methods

All randomized controlled trial (RCT) and quasi-experimental studies done prior to August 26, 2019 were included in the review. Studies were retrieved from PubMed, EMBASE, Cochrane and ScienceDirect databases including, grey and non-indexed literatures from Google and Google scholar. Quality of studies were independently assessed using Cochrane Risk of Bias Assessment Tool. A qualitative synthesis and quantitative pooled estimation were used to measure the effect of phone messaging on TB treatment success rate. PRISMA flow diagrams were used to summarize article selection process.

Results

A total of 1237 articles were identified, with 14 meeting the eligibility criteria for qualitative synthesis. Eight studies with a total of 5680 TB patients (2733 in intervention and 2947 in control groups) were included in meta-analysis. The pooled effect of mobile-phone messaging revealed a small increase in treatment success compared to standard of care (RR 1.04, 95% CI 1.02 to 1.06), with low heterogeneity (I2 = 7%, p < 0.0002). In the review, performance, detection and attrition biases were reported as major risk of biases.

Conclusions

Mobile-phone messaging showed a modest effect in improving anti-TB treatment success; however, the quality of evidence was low. Further controlled studies are needed to increase the evidence-base on the role of mHealth interventions to improve TB care.

Protocol registration number

CRD420170744339. http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42017074439