bluuebunny/crossref_metadata_2025 huggingface dataset:
Comment on “Short-lived pause in Central California subsidence after heavy winter precipitation of 2017” by K. D. Murray and R. B. Lohman
Authors: Shirzaei Manoochehr , Ojha Chandrakanta , Werth Susanna , Carlson Grace , Vivoni Enrique R.
Published: June 2019

Does a wet winter recharge deep aquifers in California?
Direct visualization of the
E. coli
Sec translocase engaging precursor proteins in lipid bilayers
Authors: Sanganna Gari Raghavendar Reddy , Chattrakun Kanokporn , Marsh Brendan P. , Mao Chunfeng , Chada Nagaraju , Randall Linda L. , King Gavin M.
Published: June 2019

We reveal the dynamic topography of active translocases as a function of precursor, nucleotide, and stage of translocation.
Spatiotemporal ontogeny of brain wiring
Authors: Goulas A. , Betzel R. F. , Hilgetag C. C.
Published: June 2019

Common principles and developmental mechanisms characterize the brain connectome of diverse species, from flies to humans.
Anti-CotH3 antibodies protect mice from mucormycosis by prevention of invasion and augmenting opsonophagocytosis
Authors: Gebremariam Teclegiorgis , Alkhazraji Sondus , Soliman Sameh S. M. , Gu Yiyou , Jeon Heewon H. , Zhang Lina , French Samuel W. , Stevens David A. , Edwards John E. , Filler Scott G. , Uppuluri Priya , Ibrahim Ashraf S.
Published: June 2019

A novel immunotherapy targeting the Mucorales unique CoH3 invasin is highly protective against murine mucormycosis.
Genomic determinants of speciation and spread of the
Mycobacterium tuberculosis
complex
Authors: Chiner-Oms Á. , Sánchez-Busó L. , Corander J. , Gagneux S. , Harris S. R. , Young D. , González-Candelas F. , Comas I.
Published: June 2019

Emergence and global success of tuberculosis involve core pathogenesis functions under selection in epidemiological settings.
Air-sea disequilibrium enhances ocean carbon storage during glacial periods
Authors: Khatiwala S. , Schmittner A. , Muglia J.
Published: June 2019

Temperature and iron fertilization are more important in driving glacial-interglacial CO
2
cycles than previously thought.
A systems genomics approach identifies
SIGLEC15
as a susceptibility factor in recurrent vulvovaginal candidiasis
Authors: Jaeger M. , Pinelli M. , Borghi M. , Constantini C. , Dindo M. , van Emst L. , Puccetti M. , Pariano M. , Ricaño-Ponce I. , Büll C. , Gresnigt M. S. , Wang X. , Gutierrez Achury J. , Jacobs C. W. M. , Xu N. , Oosting M. , Arts P. , Joosten L. A. B. , van de Veerdonk F. L. , Veltman J. A. , ten Oever J. , Kullberg B. J. , Feng M. , Adema G. J. , Wijmenga C. , Kumar V. , Sobel J. , Gilissen C. , Romani L. , Netea M. G.
Published: June 2019

SIGLEC15 is a component of the host immune response against
Candida albicans
and is dysregulated in patients with recurrent vulvovaginal candidiasis.
Hyaluronan synthase 2–mediated hyaluronan production mediates Notch1 activation and liver fibrosis
Authors: Yang Yoon Mee , Noureddin Mazen , Liu Cheng , Ohashi Koichiro , Kim So Yeon , Ramnath Divya , Powell Elizabeth E. , Sweet Matthew J. , Roh Yoon Seok , Hsin I-Fang , Deng Nan , Liu Zhenqiu , Liang Jiurong , Mena Edward , Shouhed Daniel , Schwabe Robert F. , Jiang Dianhua , Lu Shelly C. , Noble Paul W. , Seki Ekihiro
Published: June 2019

Hepatic stellate cells activated by hyaluronan synthase 2–mediated hyaluronan and Notch1 promote liver fibrosis, identifying a potential target.
Tumor-targeted 4-1BB agonists for combination with T cell bispecific antibodies as off-the-shelf therapy
Authors: Claus Christina , Ferrara Claudia , Xu Wei , Sam Johannes , Lang Sabine , Uhlenbrock Franziska , Albrecht Rosmarie , Herter Sylvia , Schlenker Ramona , Hüsser Tamara , Diggelmann Sarah , Challier John , Mössner Ekkehard , Hosse Ralf J. , Hofer Thomas , Brünker Peter , Joseph Catherine , Benz Jörg , Ringler Philippe , Stahlberg Henning , Lauer Matthias , Perro Mario , Chen Stanford , Küttel Christine , Bhavani Mohan Preethi L. , Nicolini Valeria , Birk Martina Carola , Ongaro Amandine , Prince Christophe , Gianotti Reto , Dugan Gregory , Whitlow Christopher T. , Solingapuram Sai Kiran Kumar , Caudell David L. , Burgos-Rodriguez Armando G. , Cline J. Mark , Hettich Michael , Ceppi Maurizio , Giusti Anna Maria , Crameri Flavio , Driessen Wouter , Morcos Peter N. , Freimoser-Grundschober Anne , Levitsky Victor , Amann Maria , Grau-Richards Sandra , von Hirschheydt Thomas , Tournaviti Stella , Mølhøj Michael , Fauti Tanja , Heinzelmann-Schwarz Viola , Teichgräber Volker , Colombetti Sara , Bacac Marina , Zippelius Alfred , Klein Christian , Umaña Pablo
Published: June 2019

Tumor-targeted 4-1BB agonists provide costimulation as combination partners for cancer immunotherapies in solid and hematological tumors.
Japanese Encephalitis Virus Induces Apoptosis and Encephalitis by Activating the PERK Pathway
Authors: Wang Qianruo , Xin Xiu , Wang Ting , Wan Jiawu , Ou Yangtao , Yang Zibing , Yu Qijia , Zhu Liting , Guo Yunli , Wu Yinsheng , Ding Zhen , Zhang Yanni , Pan Zishu , Tang Yuxin , Li Shanshan , Kong Lingbao
Published: June 2019

Japanese encephalitis virus (JEV) infection triggers endoplasmic reticulum (ER) stress and neuron apoptosis. ER stress sensor protein kinase R-like endoplasmic reticulum kinase (PERK) has been reported to induce apoptosis under acute or prolonged ER stress. However, whether the PERK pathway of ER stress response plays important roles in JEV-induced apoptosis and encephalitis remains unknown. Here, we found that JEV infection activates ER stress sensor PERK in neuronal cells and mouse brains. PERK activation induces apoptosis via the PERK-ATF4-CHOP apoptosis pathway upon JEV infection. Among the JEV proteins prM, E, NS1, NS2A, NS2B, and NS4B, only NS4B activates PERK. Moreover, activated PERK participates in apoptosis and encephalitis induced by JEV and NS4B. These findings provide a novel therapeutic approach for JEV-caused encephalitis.
Dense Bodies of a gH/gL/UL128/UL130/UL131 Pentamer-Repaired Towne Strain of Human Cytomegalovirus Induce an Enhanced Neutralizing Antibody Response
Authors: Lehmann Caroline , Falk Jessica Julia , Büscher Nicole , Penner Inessa , Zimmermann Christine , Gogesch Patricia , Sinzger Christian , Plachter Bodo
Published: June 2019

Infections with the human cytomegalovirus (HCMV) may cause severe and even life-threatening disease manifestations in newborns and immunosuppressed individuals. Several strategies for the development of a vaccine against this virus are currently pursued. A critical question in this respect refers to the antigenic composition of a successful vaccine. Using a subviral particle vaccine candidate, we show here that one protein complex of HCMV, termed the pentameric complex (PC), enhances the neutralizing antibody response against viral infection of different cell types. We further show for the first time that this not only relates to the infection of epithelial or endothelial cells; the presence of the PC in the particles also enhanced the neutralizing antibody response against the infection of fibroblasts by HCMV. Together, these findings argue in favor of including the PC in strategies for HCMV vaccine development.
Whole-Genome Sequence of Brucella melitensis Strain B7, Isolated from a Blood Sample of a Brucellosis Patient from Hulunbuir, Inner Mongolia, China
Authors: Zhang Guoqing , Liang Chen , Liu Chenfang , Zhang Jing , Pi Xiaoyu , Zhang Yujia , Liang Xiuwen , Wang Lijun , Zheng Beiwen
Published: June 2019

We report here the draft genome sequence of
Brucella melitensis
strain B7, isolated from a blood sample of a brucellosis patient from Hulunbuir, Inner Mongolia, China. This report describes the genome sequence of a human
B. melitensis
isolate, which is endemic in this area of China.
Draft Genome Sequence of Streptococcus anginosus Strain CALM001, Isolated from the Gut of an Elderly Dane
Authors: Ahmad Hajar Fauzan , Schreiber Lars , Marshall Ian P. G. , Andersen Philip Junker , Castro-Mejía Josué Leonardo , Nielsen Dennis Sandris
Published: June 2019

Here, we present a 1.89-Mbp draft genome sequence of
Streptococcus anginosus
strain CALM001, a Gram-positive bacterium that was isolated from a fecal sample donated by a 70-year-old Dane enrolled in the Counteracting Age-Related Loss of Skeletal Muscle Mass (CALM) intervention study.
Complete Genome Sequence of Citrobacter rodentium Strain DBS100
Authors: Popov Georgy , Fiebig-Comyn Aline , Shideler Steven , Coombes Brian K. , Savchenko Alexei
Published: June 2019

Citrobacter rodentium
strain DBS100 causes an infection of the intestines in mice. It provides an important model for human gastrointestinal pathogens, such as enteropathogenic and enterohemorrhagic
Escherichia coli
, which cause life-threatening infections. To identify the genetic determinants that are common across the enteropathogenic bacteria, we sequenced the DBS100 genome.
First Genome Sequence of Brucella abortus Biovar 3 Strain BAU21/S4023, Isolated from a Dairy Cow in Bangladesh
Authors: Islam M. Sadequl , El Zowalaty Mohamed E. , van Vliet Arnoud H. M. , Thakur Siddhartha , Khatun M. Minara , Saha Sukumar , Rahman M. Tanvir , Noreddin Ayman , Islam M. Ariful
Published: June 2019

We report the genome sequence of
Brucella abortus
biovar 3 strain BAU21/S4023, isolated from a dairy cow that suffered an abortion in Savar, Dhaka, Bangladesh. The genome sequence length is 3,244,234 bp with a 57.2% GC content, 3,147 coding DNA sequences (CDSs), 51 tRNAs, 1 transfer messenger RNA (tmRNA), and 3 rRNA genes.
Deformation of cranioplasty titanium mesh in a paediatric patient following head trauma
Authors: Sharaf Basel , Asaad Malke , Banuelos Joseph , Meaike Jesse
Published: June 2019

Decompressive craniectomy is a life-saving procedure performed to treat intracranial hypertension caused by a variety of conditions. Subsequent cranioplasty reconstruction is needed for brain protection. Different alloplastic materials with different advantages and disadvantages are available for cranial reconstruction. We present the first case of a deformed titanium cranioplasty mesh in a paediatric patient following head trauma. Children who have undergone cranioplasty reconstruction should be counselled to wear a protective helmet when involved in contact sports or activities that may put their implant at risk of trauma.
Help-seeking by male victims of domestic violence and abuse (DVA): a systematic review and qualitative evidence synthesis
Authors: Huntley Alyson L , Potter Lucy , Williamson Emma , Malpass Alice , Szilassy Eszter , Feder Gene
Published: June 2019

Objectives

To understand help-seeking by male victims of domestic violence and abuse (DVA) and their experiences of support services by systematically identifying qualitative and mixed-method studies and thematically synthesising their findings.

Design

Systematic review and qualitative evidence synthesis. Searches were conducted in 12 databases and the grey literature with no language or date restrictions. Quality appraisal of the studies was carried out using the Critical Appraisal Skills Programme tool. Reviewers extracted first and second order constructs related to help-seeking, identified themes and combined them by interpretative thematic synthesis.

Setting

DVA experienced by male victims and defined as any incident or pattern of incidents of controlling coercive or threatening behaviour, violence or abuse among people aged 18 or over who are or have been intimate partners or family members, regardless of gender or sexuality.

Participants

Male victims of DVA.

Interventions

Any intervention which provides practical and/or psychological support to male victims of DVA including but not limited to DVA-specific services, primary healthcare and sexual health clinics.

Primary and secondary outcome measures

Qualitative data describing help-seeking experiences and interactions with support services of male victims of domestic violence

Results

We included twelve studies which were published between 2006 and 2017. We grouped nine themes described over two phases (a)barriers to help-seeking: fear of disclosure, challenge to masculinity, commitment to relationship, diminished confidence/despondency and invisibility/perception of services; and (b)experiences of interventions and support: initial contact, confidentiality, appropriate professional approaches and inappropriate professional approaches.

Conclusion

The recent publication of the primary studies suggests a new interest in the needs of male DVA victims. We have confirmed previously identified barriers to help-seeking by male victims of DVA and provide new insight into barriers and facilitators to service provision.

PROSPERO registration number

CRD42016039999.
Community pharmacy lifestyle intervention to increase physical activity and improve cardiovascular health of men with prostate cancer: a phase II feasibility study
Authors: Lemanska Agnieszka , Poole Karen , Griffin Bruce A , Manders Ralph , Saxton John M , Turner Lauren , Wainwright Joe , Faithfull Sara
Published: June 2019

Objectives

To assess the feasibility and acceptability of a community pharmacy lifestyle intervention to improve physical activity and cardiovascular health of men with prostate cancer. To refine the intervention.

Design

Phase II feasibility study of a complex intervention.

Setting

Nine community pharmacies in the UK.

Intervention

Community pharmacy teams were trained to deliver a health assessment including fitness, strength and anthropometric measures. A computer algorithm generated a personalised lifestyle prescription for a home-based programme accompanied by supporting resources. The health assessment was repeated 12 weeks later and support phone calls were provided at weeks 1 and 6.

Participants

116 men who completed treatment for prostate cancer.

Outcome measures

The feasibility and acceptability of the intervention and the delivery model were assessed by evaluating study processes (rate of participant recruitment, consent, retention and adverse events), by analysing delivery data and semi-structured interviews with participants and by focus groups with pharmacy teams. Physical activity (measured with accelerometry at baseline, 3 and 6 months) and patient reported outcomes (activation, dietary intake and quality of life) were evaluated. Change in physical activity was used to inform the sample size calculations for a future trial.

Results

Out of 403 invited men, 172 (43%) responded and 116 (29%) participated. Of these, 99 (85%) completed the intervention and 88 (76%) completed the 6-month follow-up (attrition 24%). Certain components of the intervention were feasible and acceptable (eg, community pharmacy delivery), while others were more challenging (eg, fitness assessment) and will be refined for future studies. By 3 months, moderate to vigorous physical activity increased on average by 34 min (95% CI 6 to 62, p=0.018), but this was not sustained over 6 months.

Conclusions

The community pharmacy intervention was feasible and acceptable. Results are encouraging and warrant a definitive trial to assess the effectiveness of the refined intervention.
Primary care performance of alternatively licenced physicians in Ontario, Canada: a cross-sectional study using administrative data
Authors: Hodwitz Kathryn , Thakkar Niels , Schultz Susan E , Jaakkimainen Liisa , Faulkner Daniel , Yen Wendy
Published: June 2019

Objectives

Medical Regulatory Authorities (MRAs) provide licences to physicians and monitor those physicians once in practice to support their continued competence. In response to physician shortages, many Canadian MRAs developed alternative licensure routes to allow physicians who do not meet traditional licensure criteria to obtain licences to practice. Many physicians have gained licensure through alternative routes, but the performance of these physicians in practice has not been previously examined. This study compared the performance of traditionally and alternatively licenced physicians in Ontario using quality indicators of primary care. The purpose of this study was to examine the practice performance of alternatively licenced physicians and provide evaluative evidence for alternative licensure policies.

Design

A cross-sectional retrospective examination of Ontario health administrative data was conducted using Poisson regression analyses to compare the performance of traditionally and alternatively licenced physicians.

Setting

Primary care in Ontario, Canada.

Participants

All family physicians who were licenced in Ontario between 2000 and 2012 and who had complete medical billing data in 2014 were included (n=11 419).

Outcome measures

Primary care quality indicators were calculated for chronic disease management, preventive paediatric care, cancer screening and hospital readmission rates using Ontario health administrative data.

Results

Alternatively licenced physicians performed similarly to traditionally licenced physicians in many primary care performance measures. Minimal differences were seen across groups in indicators of diabetic care, congestive heart failure care, asthma care and cancer screening rates. Larger differences were found in preventive care for children less than 2 years of age, particularly for alternatively licenced physicians who entered Ontario from another Canadian province.

Conclusions

Our findings demonstrate that alternatively licenced physicians perform similarly to traditionally licenced physicians across many indicators of primary care. Our study also demonstrates the utility of administrative data for examining physician performance and evaluating medical regulatory policies and programmes.
Effect of an integrated care pathway on use of primary and secondary healthcare by patients at high risk of emergency inpatient admission: a matched control cohort study in Tower Hamlets
Authors: Parry Will , Wolters Arne Timon , Brine Richard James , Steventon Adam
Published: June 2019

Objectives

To assess the effects of an integrated care pathway on the use of primary and secondary healthcare by patients at high risk of emergency inpatient admission.

Design

Observational study of a real-life deployment of integrated care, using patient-level administrative data. Regression analysis was used to compare integrated care patients with matched controls.

Setting

A deprived, inner city London borough (Tower Hamlets).

Participants

1720 patients aged 50+ years registered with a general practitioner in Tower Hamlets and at high risk of emergency inpatient admission enrolled onto integrated care during 2014. These patients were matched to control patients, also selected from Tower Hamlets, with respect to demographics, diagnoses of health conditions, previous hospital use and risk score.

Interventions

Enrolled patients were eligible for a range of interventions, such as case management, support with self-care and enhanced care coordination. Control patients received usual care.

Primary and secondary endpoints

Number of emergency inpatient admissions in the year after enrolment onto integrated care. Secondary endpoints included numbers of elective inpatient admissions, inpatient bed days, accident and emergency attendances, outpatient attendances and general practitioner contacts in the year after enrolment.

Results

There was no evidence that the integrated care pathway reduced patients’ healthcare utilisation in the first year post-enrolment. Matched controls and integrated care patients were similar at baseline. Following enrolment, integrated care patients were more likely than matched controls to experience elective inpatient admissions (adjusted incidence rate ratio (IRR)=1.27, 95% CI 1.08 to 1.49, p=0.004). They were also more likely to experience general practitioner contacts (adjusted IRR=1.11, 95% CI 1.06 to 1.16, p<0.001), but other endpoints were not significantly different between the groups.

Conclusions

The integrated care pathway was not associated with a reduction in healthcare utilisation in the first year, but appeared to have increased elective inpatient admissions and general practitioner workload.
Changes in hepatitis C burden and treatment trends in Europe during the era of direct-acting antivirals: a modelling study
Authors: Chen Qiushi , Ayer Turgay , Bethea Emily , Kanwal Fasiha , Wang Xiaojie , Roberts Mark , Zhuo Yueran , Fagiuoli Stefano , Petersen Jorg , Chhatwal Jagpreet
Published: June 2019

Objectives

Oral direct-acting antivirals (DAAs) for hepatitis C virus (HCV) have dramatically changed the treatment paradigm. Our aim was to project temporal trends in HCV diagnosis, treatment and disease burden in France, Germany, Italy, Spain and the UK.

Design

A mathematical simulation model of natural history of HCV infection.

Participants

HCV-infected patients defined based on country-specific age, fibrosis and genotype distributions.

Interventions

HCV screening practice and availability of different waves of DAA treatment in each country.

Outcome measures

Temporal trends in the number of patients who achieve sustained virological response (SVR), fail treatment (by drug regimen) and develop advanced sequelae from 2014 to 2030 in each country.

Results

We projected that 1 324 000 individuals would receive treatment from 2014 to 2030 in the five European countries and 12 000–37 000 of them would fail to achieve SVR. By 2021, the number of individuals cured of HCV would supersede the number of actively infected individuals in France, Germany, Spain and the UK. Under status quo, the diagnosis rate would reach between 65% and 75% and treatment coverage between 65% and 74% by 2030 in these countries. The number of patients who fail treatment would decrease over time, with the majority of those who fail treatment having been exposed to non-structural protein 5A inhibitors.

Conclusions

In the era of DAAs, the number of people with HCV who achieved a cure will exceed the number of viraemic patients, but many patients will remain undiagnosed, untreated, fail multiple treatments and develop advanced sequelae. Scaling-up screening and treatment capacity, and timely and effective retreatment are needed to avail the full benefits of DAAs and to meet HCV elimination targets set by WHO.
Knowledge and practice of hand hygiene among hospitalised patients in a tertiary general hospital in China and their attitudes: a cross-sectional survey
Authors: Li Yunxia , Liu Yaohong , Zeng Li , Chen Chong , Mo Dan , Yuan Sue
Published: June 2019

Objectives

We aimed to gain a better understanding of patients’ practice of hand hygiene (HH) and their knowledge and attitudes.

Design

A cross-sectional survey.

Setting

A 3500-bed university-affiliated medical hospital in China.

Participants

Inpatients and their family members or caregivers.

Methods

An anonymous, self-reported questionnaire were used to collect data.

Results

A total of 376 questionnaires were issued, and 310 respondents completed it. Of the 310 respondents, 47.4% had received HH education, and 13.5% had a completing understanding of HH. A majority of patients believed that handwashing was important for disease recovery, and that it could prevent infection development. A total of 62.3% of patients washed their hands <5 times a day and 49.0% spent <1 min every time. With regards to the seven steps of handwashing, 96.45% of the respondents adhered to the first step (washing the palms), but only 20.6% adhered to the fifth step (thumbs) and 17.7% to the sixth step (fingertips). Most respondents washed their hands only when visibly dirty. Few patients washed their hands before drinking fluids, and before and after interacting with visitors. HH compliance was lower among intensive care unit patients than medical patients.

Conclusions

In conclusion, this study demonstrated that patients had a positive attitude towards HH. However, their levels of knowledge and practice were unsatisfactory. A systematical education about patientHH is needed in future to correct this knowledge and behaviour.
WHO recommendations on physical activity versus compliance rate within a specific urban population as assessed through IPAQ survey: a cross-sectional cohort study
Authors: Macek Pawel , Terek-Derszniak Malgorzata , Zak Marek , Biskup Malgorzata , Ciepiela Przemyslaw , Krol Halina , Smok-Kalwat Jolanta , Gozdz Stanislaw
Published: June 2019

Objective

The study was designed to address the following three key areas, that is, (1) evaluate overall level of physical activity in the residents of a mid-sized, Central-European city, (2) compliance level with WHO’s recommendations on physical activity in leisure time and (3) actual impact of select socioeconomic factors on the physical activity level within the study population.

Methods

Assessment of the source data collected for 4619 participants (1532 men and 3087 women, aged 45–65 years; mean age 56.41±5.31 years) was completed. Three levels of physical activity, and compliance level with pertinent WHO recommendations was evaluated, based on International Physical Activity Questionnaire (long form). Multilevel logistic regression models of socioeconomic factors associated with moderate-level, high-level physical activity, and WHO recommendations were developed.

Results

Data analyses revealed that 6.19% of the study participants (n=286) engaged in low-level physical activity, 48.86%—in moderate-level activity, while high-level activity was reported in 44.94% of them. Compliance with pertinent WHO recommendations was higher in men aged 44–55 years, boasting upper-level education, living without a partner and in the persons with a net income over €1140 per household.

Conclusions

Overall level of physical activity in the residents of a mid-sized, Central-European city was established as moderate. Pertinent WHO recommendations on physical activity were met by 4.2% of the subjects only.
Trainee doctors’ experiences of common problems in the antibiotic prescribing process: an activity theory analysis of narrative data from UK hospitals
Authors: Kajamaa Anu , Mattick Karen , Parker Hazel , Hilli Angelique , Rees Charlotte
Published: June 2019

Introduction

Prescribing antibiotics is an error-prone activity and one of the more challenging responsibilities for doctors in training. The nature and extent of challenges experienced by them at different stages of the antibiotic prescribing process are not well described, meaning that interventions may not target the most problematic areas.

Objectives

Our aim was to explore doctors in training experiences of common problems in the antibiotic prescribing process using cultural–historical activity theory (CHAT). Our research questions were as follows: What are the intended stages in the antibiotic prescribing process? What are the challenges and where in the prescribing process do these occur?

Methods

We developed a process model based on how antibiotic prescribing is intended to occur in a ‘typical’ National Health Service hospital in the UK. The model was first informed by literature and refined through consultation with practising healthcare professionals and medical educators. Then, drawing on CHAT, we analysed 33 doctors in training narratives of their antibiotic prescribing experiences to identify and interpret common problems in the process.

Results

Our analysis revealed five main disturbances commonly occurring during the antibiotic prescribing process: consultation challenges, lack of continuity, process variation, challenges in patient handover and partial loss of object. Our process model, with 31 stages and multiple practitioners, captures the complexity, inconsistency and unpredictability of the process. The model also highlights ‘hot spots’ in the process, which are the stages that doctors in training are most likely to have difficulty navigating.

Conclusions

Our study widens the understanding of doctors in training prescribing experiences and development needs regarding the prescribing process. Our process model, identifying the common disturbances and hot spots in the process, can facilitate the development of antibiotic prescribing activities and the optimal design of interventions to support doctors in training.
Protocol for a feasibility study of a cohort embedded randomised controlled trial comparingNEphronSparingTreatment (NEST) for small renal masses
Authors: Neves Joana B , Cullen David , Grant Lee , Walkden Miles , Bandula Steve , Patki Prasad , Barod Ravi , Mumtaz Faiz , Aitchison Michael , Pizzo Elena , Ranieri Veronica , Williams Norman , Wildgoose William , Gurusamy Kurinchi , Emberton Mark , Bex Axel , Tran Maxine G B
Published: June 2019

Introduction

Small renal masses (SRMs; ≤4 cm) account for two-thirds of new diagnoses of kidney cancer, the majority of which are incidental findings. The natural history of the SRM seems largely indolent. There is an increasing concern regarding surgical overtreatment and the associated health burden in terms of morbidity and economy. Observational data support the safety and efficacy of percutaneous cryoablation but there is an unmet need for high-quality evidence on non-surgical management options and a head-to-head comparison with standard of care is lacking. Historical interventional trial recruitment difficulties demand novel study conduct approaches. We aim to assess if a novel trial design, the cohort embedded randomised controlled trial (RCT), will enable carrying out such a comparison.

Methods and analysis

Single-centre prospective cohort study of adults diagnosed with SRM (n=200) with an open label embedded interventional RCT comparing nephron sparing interventions. Cohort participants will be managed at patient and clinicians’ discretion and agree with longitudinal clinical data and biological sample collection, with invitation for trial interventions and participation in comparator control groups. Cohort participants with biopsy-proven renal cell carcinoma eligible for both percutaneous cryoablation and partial nephrectomy will be randomly selected (1:1) and invited to consider percutaneous cryoablation (n=25). The comparator group will be robotic partial nephrectomy (n=25). The primary outcome of this feasibility study is participant recruitment. Qualitative research techniques will assess barriers and recruitment improvement opportunities. Secondary outcomes are participant trial retention, health-related quality of life, treatment complications, blood transfusion rate, intensive care unit admission and renal replacement requirement rates, length of hospital stay, time to return to pre-treatment activities, number of work days lost, and health technologies costs.

Ethics and dissemination

Ethical approval has been granted (UK HRA REC 19/EM/0004). Study outputs will be presented and published.

Trial registration

ISRCTN18156881; Pre-results.
Short-Run Bond Risk Premia
Authors: Mueller Philippe , Vedolin Andrea , Zhou Hao
Published: June 2019

In the short-run, bond risk premia exhibit pronounced spikes around major economic and financial crises. In contrast, long-term bond risk premia feature cyclical swings. We empirically examine the predictability of the market variance risk premium — a proxy of economic uncertainty — for bond risk premia and we show the strong predictive power for the one-month horizon that quickly recedes for longer horizons. The variance risk premium is largely orthogonal to well-established bond return predictors — forward rates, jumps, and macro variables. We rationalize our empirical findings in an equilibrium model of uncertainty about consumption and inflation which is coupled with recursive preferences. We show that the model can quantitatively explain the levels of bond and variance risk premia as well as the predictive power of the variance risk premium, while jointly matching salient features of other asset prices.
Education for Sustainable Development: Global Progress and China’s Experience
Authors: LI Chunling
Published: June 2019

Education for Sustainable Development (ESD) is a key component of the concept of sustainable social development advocated by the international community. The international community has successively set periodic goals for ESD, e.g. The Dakar Framework for Action and Education 2030 Framework for Action, to advance universal education that is conducive to global equity and quality development. According to the Global Education Monitoring (GEM) reports of UNESCO, ESD has made great strides on many fronts worldwide since 2000, but the gaps between countries with different incomes and levels of development remain significant, and gender and class inequalities in educational opportunities persist. China has yielded substantial results in ESD with all its indexes reaching or even surpassing the goals set in The Dakar Framework for Action. And in response to the Education 2030 Framework for Action, the Chinese Government is formulating Education 2030: Modernization of Education in China to guide China’s ESD, with the aim to raise the level of education for all, gradually address the educational inequalities among regions, between urban and rural areas, and among different social strata, and develop more inclusive and equitable quality education, thus achieving the goal of lifelong education for all.
Laser-Assisted Reconstruction of Vibro-Acoustic Behaviors of an Arbitrarily Shaped Vibrating Structure
Authors: Wu Sean F. , Chen Lingguang , Figueroa Antonio , Telenko Michael
Published: June 2019

This paper presents a new method known as laser-assisted, modified Helmholtz Equation Least Squares method-based reconstruction to determine vibro-acoustic quantities of an arbitrarily shaped vibrating structure subject to a noncontact acoustic excitation. Unlike the traditional near-field acoustical holography (NAH) that relies on the acoustic pressures measured in the near-field, this new methodology enables one to collect the input data at a remote distance by using a laser vibrometer, making measurement setup much easier than all previous NAH approaches. Most importantly, by measuring the normal components of the surface velocities at the accessible areas, one can acquire near-field information of a vibrating structure directly, rather than indirectly through reconstruction based on the acoustic pressures measured in the near field. To ensure the accuracy in reconstruction of all the vibro-acoustic characteristics of a structure, the acoustic pressures at a few points in space are also measured. By combining these partial input data, one can acquire a complete picture of the vibro-acoustic field of an arbitrarily shaped vibrating structure, which includes operation deflection shapes, distributions of the acoustic pressures and the normal component of the acoustic intensities on a source surface, and the time-averaged acoustic power of the structure. When the input power is specified, one may determine the frequency response functions, the natural modes, the structural damping ratios of the structure, sound transmission loss, sound transmission path, etc. Examples of using this technology to acquire an in-depth understanding of the vibro-acoustic characteristics of an automobile front dash panel are presented.
Basement membrane-like structures containing NTH α1(IV) are formed around the endothelial cell network in a novel in vitro angiogenesis model
Authors: Shin Yongchol , Moriya Akane , Tohnishi Yuta , Watanabe Takafumi , Imamura Yasutada
Published: June 2019

Angiogenesis is a process through which new blood vessels are formed by sprouting and elongating from existing blood vessels. Several methods have been used to replicate angiogenesis in vitro, including culturing vascular endothelial cells on Matrigel and coculturing with endothelial cells and fibroblasts. However, the angiogenesis elongation process has not been completely clarified in these models. We therefore propose a new in vitro model of angiogenesis, suitable for observing vascular elongation, by seeding a spheroid cocultured from endothelial cells and fibroblasts into a culture dish. In this model, endothelial cells formed tubular networks elongated from the spheroid with a lumen structure and were connected with tight junctions. A basement membrane (BM)-like structure was observed around the tubular network, similarly to blood vessels in vivo. These results suggested that blood vessel-like structure could be reconstituted in our model. Laminin and type IV collagen, main BM components, were highly localized around the network, along with nontriple helical form of type IV collagen α1-chain [NTH α1(IV)]. In an ascorbic acid-depleted condition, laminin and NTH α1(IV) were observed around the network but not the triple-helical form of type IV collagen and the network was unstable. These results suggest that laminin and NTH α1(IV) are involved in the formation of tubular network and type IV collagen is necessary to stabilize the network.
Skeletal muscle LINE-1 retrotransposon activity is upregulated in older versus younger rats
Authors: Mumford Petey W. , Romero Matthew A. , Osburn Shelby C. , Roberson Paul A. , Vann Christopher G. , Mobley Christopher B. , Brown Michael D. , Kavazis Andreas N. , Young Kaelin C. , Roberts Michael D.
Published: June 2019

Long interspersed element-1 (LINE-1) is a retrotransposon capable of replicating and inserting LINE-1 copies into the genome. Others have reported skeletal muscle LINE-1 markers are higher in older versus younger mice, but data are lacking in other species. Herein, gastrocnemius muscle from male Fischer 344 rats that were 3, 12, and 24 mo old ( n = 9 per group) were analyzed for LINE-1 mRNA, DNA, promoter methylation and DNA accessibility. qPCR primers were designed for active (L1.3) and inactive (L1.Tot) LINE-1 elements as well as part of the ORF1 sequence. L1.3, L1.Tot, and ORF1 mRNAs were higher ( P < 0.05) in 12/24 versus 3-mo-old rats. L1.3 DNA was higher in the 24-mo-old rats versus other groups, and ORF1 DNA was greater in 12/24 versus 3-mo-old rats. ORF1 protein was higher in 12/24 versus 3-mo-old rats. RNA-sequencing indicated mRNAs related to DNA methylation ( Tet1) and histone acetylation ( Hdac2) were lower in 24 versus 3-mo-old rats. L1.3 DNA accessibility was higher in 24-mo-old versus 3-mo-old rats. No age-related differences in nuclear histone deacetylase (HDAC) activity existed, although nuclear DNA methyltransferase (DNMT) activity was lower in 12/24 versus 3-mo-old rats ( P < 0.05). In summary, markers of skeletal muscle LINE-1 activity increase across the age spectrum of rats, and this may be related to deficits in DNMT activity and/or increased LINE-1 DNA accessibility.
Flexural Response of Steel‐Concrete Composite Truss Beams
Authors: Luo Lisheng , Zhang Xiaofeng
Published: June 2019

This paper presents an experimental and analytical study on the flexural response of a steel‐concrete composite truss beam. This integrated unit consists of a triangular steel truss, a concrete slab on it, and stud connectors. Three simply supported composite trusses with different configurations of shear connection (η) were evaluated via three‐point bending tests. The effects of the shear connectors’ configuration on the flexural response (i.e., load‐deflection, load‐slippage, and load‐strain curves) of the composite trusses were examined. The commercial finite‐element (FE) software ANSYS was employed to conduct numerical simulations. An FE model was developed for the composite truss and was validated using experimental results. A parametric study was performed to investigate the effect of the shear connectors’ configuration on the flexural response of the composite trusses. If η < 1, the bending capacity increased with η. In contrast, if η ≥ 1, the effect of η on the bending capacity was negligible. Finally, a design method based on the degree of the shear connection was proposed to predict the ultimate capacity of the composite truss, and the predictions agreed well with the experimental results.
Expression Profiling of Exosomal miRNAs Derived from the Peripheral Blood of Kidney Recipients with DGF Using High-Throughput Sequencing
Authors: Wang Junpeng , Li Xin , Wu Xiaoqiang , Wang Zhiwei , Zhang Chan , Cao Guanghui , Yan Tianzhong
Published: June 2019

Delayed graft function (DGF) is one of the major obstacles for graft survival for kidney recipients. It is profound to reduce the incidence of DGF for maintaining long-term graft survival. However, the molecular regulation of DGF is still not adequately explained and the biomarkers for DGF are limited. Exosomes are cell-derived membrane vesicles, contents of which are stable and could be delivered into recipient cells to exert their biological functions. Consequently, exosome-derived proteomic and RNA signature profiles are often used to account for the molecular regulation of diseases or reflect the conditional state of their tissue as biomarkers. Few researches have been done to demonstrate the function of exosomes associated with DGF. In this study, high-throughput sequencing was used to explore the miRNA expression profiling of exosomes in the peripheral blood of kidney recipients with DGF. We identified 52 known and 5 conserved exosomal miRNAs specifically expressed in recipients with DGF. Three coexpressed miRNAs, hsa-miR-33a-5p_R-1, hsa-miR-98-5p, and hsa-miR-151a-5p, were observed to be significantly upregulated in kidney recipients with DGF. Moreover, hsa-miR-151a-5p was positively correlated with the first-week serum CR, BUN, and UA levels of the kidney recipients after transplantation. Furthermore, we also analyzed functions and signaling pathways of the three upregulated miRNAs target genes to uncover putative mechanism of how these exosomal miRNAs functioned in DGF. Overall, these findings identified biomarker candidates for DGF and provided new insights into the important role of the exosomal miRNAs regulation in DGF.
Personality and Personality Disorders in Medication-Overuse Headache: A Controlled Study by SWAP-200
Authors: Galli Federica , Tanzilli Annalisa , Simonelli Alessandra , Tassorelli Cristina , Sances Grazia , Parolin Micol , Cristofalo Patrizia , Gualco Ivan , Lingiardi Vittorio
Published: June 2019

Background. Medication-overuse headache (MOH) is a type of chronic headache, whose mechanisms are still unknown. The impact of psychological factors has been matter of debate from different perspectives. The role of personality and personality pathology in processes involved in MOH development has been advanced but was poorly studied. The hypothesis of addiction-like behaviors sustaining the drug misuse has been examined and reached contrasting findings.Objectives. This study is aimed at detecting personality and its disorders (PDs) in MOH, with a specific attention to the addiction aspect.Methods. Eighty-eight MOH patients have been compared with two clinical populations including 99 patients with substance use disorder (SUD) and 91 with PDs using the Shedler-Westen Assessment Procedure-200 (SWAP-200), a clinician-report tool that assesses both normal and pathological personality. MANCOVAs were performed to evaluate personality differences among MOH, SUD, and PD groups, controlling for age and gender.Results. MOH patients were predominantly women and older. They showed lower traits of the SWAP-200’s cluster A and B disorders than SUD and PD patients, who presented more severe levels of personality impairment. No differences in the SWAP-200’s cluster C have been found, indicating common personality features in these populations. At levels of specific PDs, MOH patients showed higher obsessive and dysphoric traits and better overall psychological functioning than SUD and PD patients.Conclusion. Although MOH, SUD, and PD populations have been evaluated in multiple sites with different levels of expertise, the study supported the presence of a specific constellation of personality in MOH patients including obsessive (perfectionist) and dysphoric characteristics, as well as good enough psychological resources. No similarities to drug-addicted and personality-disordered patients were found. Practitioners’ careful understanding of the personality characteristics of MOH patients may be useful to provide a road map for the implementation of more effective treatment strategies and intervention programs.
Local versus Global Models for Just-In-Time Software Defect Prediction
Authors: Yang Xingguang , Yu Huiqun , Fan Guisheng , Shi Kai , Chen Liqiong
Published: June 2019

Just-in-time software defect prediction (JIT-SDP) is an active topic in software defect prediction, which aims to identify defect-inducing changes. Recently, some studies have found that the variability of defect data sets can affect the performance of defect predictors. By using local models, it can help improve the performance of prediction models. However, previous studies have focused on module-level defect prediction. Whether local models are still valid in the context of JIT-SDP is an important issue. To this end, we compare the performance of local and global models through a large-scale empirical study based on six open-source projects with 227417 changes. The experiment considers three evaluation scenarios of cross-validation, cross-project-validation, and timewise-cross-validation. To build local models, the experiment uses the k-medoids to divide the training set into several homogeneous regions. In addition, logistic regression and effort-aware linear regression (EALR) are used to build classification models and effort-aware prediction models, respectively. The empirical results show that local models perform worse than global models in the classification performance. However, local models have significantly better effort-aware prediction performance than global models in the cross-validation and cross-project-validation scenarios. Particularly, when the number of clusters k is set to 2, local models can obtain optimal effort-aware prediction performance. Therefore, local models are promising for effort-aware JIT-SDP.
A Comprehensive Evaluation of the Association between Polymorphisms in XRCC1, ERCC2, and XRCC3 and Prognosis in Hepatocellular Carcinoma: A Meta-Analysis
Authors: Zhao Yan , Zhao Erjiang , Zhang Junhui , Chen Yuanyuan , Ma Junli , Li Hailiang
Published: June 2019

Purpose. Associations between XRCC1, XRCC3, and ERCC2 gene polymorphism and prognosis have been investigated in several cancers. The aim of this meta-analysis was to assess the prognostic value of XRCC1, XRCC3, and ERCC2 gene polymorphism in hepatocellular carcinoma (HCC). Methods. A systematic literature search was performed to identify relevant studies in PubMed, Embase, and the Cochrane library up to December 2018. The prognostic values of XRCC1, XRCC3, and ERCC2 polymorphisms in HCC were estimated using crude HRs with 95% CIs. Results. Ten studies involving 2687 patients were included in the quantitative analysis. There were no statistically significant associations between XRCC1 rs1799782 C>T, XRCC1 rs25487 G>A, and ERCC2 rs1799793 G>A polymorphisms and overall survival (OS). OS was significantly longer for the ERCC2 rs13181 CC genotype than for AA (CC vs. AA: HR = 0.33, 95% CI = 0.15–0.72). A significantly lower OS was observed for patients with the CT genotype compared with the CC genotype at XRCC3 rs861539 (CT vs. CC: HR = 1.64, 95% CI = 1.11–2.42). Conclusion. The ERCC2 rs13181 A>C polymorphism and XRCC3 rs861539 C>T polymorphism may be predictive markers for prognosis in patients with HCC. Well-designed studies with larger sample sizes are needed to verify our findings.