bluuebunny/crossref_metadata_2025 huggingface dataset:
Natureza, graça e cristianismo anônimo em Rahner
Authors: Ribeiro Almeida Juliano
Published: May 2019

Karl Rahner, ao articular natureza e graça em teologia sistemática, traz da escolástica para os desafios do nosso tempo o conceito de “cristãos anônimos”, que, depois de já se considerar superado por teólogos do diálogo inter-religioso de décadas atrás, volta ao cenário atual como relevante devido à nova onda de enrijecimento de alas conservadoras do catolicismo. Este artigo, refazendo o percurso trilhado por Rahner, investiga os sempre novos caminhos da graça divina, que deseja salvar a todos e todas, dentro e fora do mundo das religiões.
Mechanical Characteristics of Origami Mechanism Based on Thin Plate Bending Theory
Authors: Hongying Yu , Zhen Guo , Di Zhao , Peng Liu
Published: May 2019

This paper introduces a method for calculating the deformation displacement of the origami mechanism. The bearing capacity of each face can be analyzed by the relationship between the stress and displacement, which can provide a reference for the origami design. The Miura origami mechanism unit is considered. First, the folding angle of each crease is solved based on the geometric characteristics. The deforming form of the creases is then analyzed, and the bending moment acting on the paper surface is solved. Based on the geometric characteristics and stress forms, the paper surface is modeled as a sheet. Based on the bending theory of a thin plate with small deflection, the complex external load forms are decomposed by Levy's method and the superposition principle, and the expression of the deflection curve during the folding process is obtained. According to the stress and bending moment equations, the relationship between the bending moment and displacement is obtained. Finally, through an application example, the maximum deflection of the paper surface is calculated by matlab, and the deflection diagram of the deformed paper surface is drawn, which verifies the expression of the deflection curve.
Effect of Wall Elasticity on Hemodynamics and Wall Shear Stress in Patient-Specific Simulations in the Coronary Arteries
Authors: Eslami Parastou , Tran Justin , Jin Zexi , Karady Julia , Sotoodeh Romina , Lu Michael T. , Hoffmann Udo , Marsden Alison
Published: May 2019

Wall shear stress (WSS) has been shown to be associated with myocardial infarction (MI) and progression of atherosclerosis. Wall elasticity is an important feature of hemodynamic modeling affecting WSS calculations. The objective of this study was to investigate the role of wall elasticity on WSS, and justify use of either rigid or elastic models in future studies. Digital anatomic models of the aorta and coronaries were created based on coronary computed tomography angiography (CCTA) in four patients. Hemodynamics was computed in rigid and elastic models using a finite element flow solver. WSS in five timepoints in the cardiac cycle and time averaged wall shear stress (TAWSS) were compared between the models at each 3 mm subsegment and 4 arcs in cross sections along the centerlines of coronaries. In the left main (LM), proximal left anterior descending (LAD), left circumflex (LCX), and proximal right coronary artery (RCA) of the elastic model, the mean percent radial increase 5.95 ± 1.25, 4.02 ± 0.97, 4.08 ± 0.94, and 4.84 ± 1.05%, respectively. WSS at each timepoint in the cardiac cycle had slightly different values; however, when averaged over the cardiac cycle, there were negligible differences between the models. In both the subsegments (n = 704) and subarc analysis, TAWSS in the two models were highly correlated (r = 0.99). In investigation on the effect of coronary wall elasticity on WSS in CCTA-based models, the results of this study show no significant differences in TAWSS justifying using rigid wall models for future larger studies.
Noncommutativity of Finite Rotations and Definitions of Curvature and Torsion
Authors: Shabana Ahmed A. , Ling Hao
Published: May 2019

The geometry of a space curve, including its curvature and torsion, can be uniquely defined in terms of only one parameter which can be the arc length parameter. Using the differential geometry equations, the Frenet frame of the space curve is completely defined using the curve equation and the arc length parameter only. Therefore, when Euler angles are used to describe the curve geometry, these angles are no longer independent and can be expressed in terms of one parameter as field variables. The relationships between Euler angles used in the definition of the curve geometry are developed in a closed-differential form expressed in terms of the curve curvature and torsion. While the curvature and torsion of a space curve are unique, the Euler-angle representation of the space curve is not unique because of the noncommutative nature of the finite rotations. Depending on the sequence of Euler angles used, different expressions for the curvature and torsion can be obtained in terms of Euler angles, despite the fact that only one Euler angle can be treated as an independent variable, and such an independent angle can be used as the curve parameter instead of its arc length, as discussed in this paper. The curve differential equations developed in this paper demonstrate that the curvature and torsion expressed in terms of Euler angles do not depend on the sequence of rotations only in the case of infinitesimal rotations. This important conclusion is consistent with the definition of Euler angles as generalized coordinates in rigid body dynamics. This paper generalizes this definition by demonstrating that finite rotations cannot be directly associated with physical geometric properties or deformation modes except in the cases when infinitesimal-rotation assumptions are used.
Maximum Entropy Method-Based Reliability Analysis With Correlated Input Variables via Hybrid Dimension-Reduction Method
Authors: He Wanxin , Li Gang , Hao Peng , Zeng Yan
Published: May 2019

The estimation of the statistical moments is widely involved in the industrial application, whose accuracy affects the reliability analysis result considerably. In this study, a novel hybrid dimension-reduction method based on the Nataf transformation is proposed to calculate the statistical moments of the performance function with correlated input variables. Nataf transformation is intrinsically the Gaussian copula, which is commonly used to transform the correlated input variables into independent ones. To calculate the numerical integration of the univariate component function in the proposed method, a normalized moment-based quadrature rule is employed. According to the statistical moments obtained by the proposed method, the probability density function of the performance function can be recovered accurately via maximum entropy method. Six examples are tested to illustrate the accuracy and efficiency of the proposed method, compared with that of Monte Carlo simulation, the conventional univariate dimension-reduction method, and the bivariate dimension-reduction method. It is confirmed that the proposed method achieves a good tradeoff between accuracy and efficiency for structural reliability analysis with correlated input variables.
Detecting nanometric displacements with optical ruler metrology
Authors: Yuan Guang Hui , Zheludev Nikolay I.
Published: May 2019

Superoscillatory displacement metrology

The resolving power of light (or other waveforms, for that matter) is typically limited to about half the wavelength. However, multiple interference of waves gives rise to subwavelength “hotspots” in the phase owing to what is termed superoscillation of the wave field. Yuan and Zheludev used a specially designed metasurface to interfere laser light (wavelength λ = 800 nm) and created a superoscillatory ruler comprising these hotspots. They demonstrated the ability to measure displacements of around λ/800 while operating at a wavelength of 800 nm. They then showed theoretically that resolving powers of around λ/4000, i.e., atomic-scale displacements, may be possible. The technique should prove useful to metrology applications requiring precision measurements.

Science
, this issue p.
771
Site-selective enzymatic C‒H amidation for synthesis of diverse lactams
Authors: Cho Inha , Jia Zhi-Jun , Arnold Frances H.
Published: May 2019

The right bond in the right place

Enzymes excel at specificity because of their constrained active sites. With appropriate evolutionary pressure, they can be made to differentiate between similar substrates or between positions on a single substrate. Cho
et al.
used directed evolution to generate cytochrome P450 variants that target different C–H bonds in substrates, forming lactam rings of varying size (see the Perspective by Hepworth and Flitsch). The enzyme directs amidation to the desired position and simultaneously prevents other side reactions.

Science
, this issue p.
575
; see also p.
529
Efficient Inactivation of Clinically Relevant Antimicrobial Drug Concentrations by BacT/Alert or Bactec Resin-Containing Media in Simulated Adult Blood Cultures
Authors: Menchinelli Giulia , Liotti Flora Marzia , Giordano Liliana , De Angelis Giulia , Sanguinetti Maurizio , Spanu Teresa , Posteraro Brunella
Published: May 2019

We assessed the antimicrobial-inactivation capability of BacT/Alert (FA Plus and FN Plus) or Bactec (Plus Aerobic/F and Plus Anaerobic/F) media for 40 antibiotic-bacterium combinations in simulated adult blood cultures. Aside from high recovery rates (93.2% and 88.4%, respectively), we showed that at the lowest but clinically relevant antibiotic concentrations, both BacT/Alert and Bactec media recovered all the organisms tested with drugs except for
Escherichia coli
, which was tested in the presence of meropenem.
Host Specificity and Sensitivity of Established and Novel Sewage-Associated Marker Genes in Human and Nonhuman Fecal Samples
Authors: Ahmed Warish , Gyawali Pradip , Feng Shuchen , McLellan Sandra L.
Published: May 2019

Large financial investments are required to remediate fecal contamination sources in waterways, and accurate results from field studies are crucial to build confidence in MST approaches. Host specificity and sensitivity are two main performance characteristics for consideration when choosing MST assays. Ongoing efforts for marker assay validation will improve interpretation of results and could shed light on patterns of occurrence in nontarget hosts that might explain the underlying drivers of cross-reaction of certain markers. For field applications, caution should be taken to choose appropriate MST marker genes and assays based on available host specificity and sensitivity data and background knowledge of the contaminating sources in the study area. Since many waterborne pathogens are viruses, employing both viral and bacterial markers in investigations could provide insight into contamination dynamics and ecological behavior in the environment. Therefore, combined usage of marker assays is recommended for more accurate and informative sewage contamination detection and fecal source resolution.
Delineating Surface Epitopes of Lyme Disease Pathogen Targeted by Highly Protective Antibodies of New Zealand White Rabbits
Authors: Rogovskyy Artem S. , Caoili Salvador Eugenio C. , Ionov Yurij , Piontkivska Helen , Skums Pavel , Tsyvina Viachaslau , Zelikovsky Alex , Waghela Suryakant D.
Published: May 2019

Lyme disease (LD), the most prevalent vector-borne illness in the United States and Europe, is caused by
Borreliella burgdorferi
. No vaccine is available for humans. Dogmatically,
B. burgdorferi
can establish a persistent infection in the mammalian host (e.g., mice) due to a surface antigen, VlsE. This antigenically variable protein allows the spirochete to continually evade borreliacidal antibodies.
Recombination of the Phase-Variable
spnIII
Locus Is Independent of All Known Pneumococcal Site-Specific Recombinases
Authors: De Ste Croix M. , Chen K. Y. , Vacca I. , Manso A. S. , Johnston C. , Polard P. , Kwun M. J. , Bentley S. D. , Croucher N. J. , Bayliss C. D. , Haigh R. D. , Oggioni M. R.
Published: May 2019

Streptococcus pneumoniae
is a leading cause of pneumonia, septicemia, and meningitis. The discovery that genetic rearrangements in a type I restriction-modification locus can impact gene regulation and colony morphology led to a new understanding of how this pathogen switches from harmless colonizer to invasive pathogen. These rearrangements, which alter the DNA specificity of the type I restriction-modification enzyme, occur across many different pneumococcal serotypes and sequence types and in the absence of all known pneumococcal site-specific recombinases. This finding suggests that this is a truly global mechanism of pneumococcal gene regulation and the need for further investigation of mechanisms of site-specific recombination.
UK trainee-led paediatric governance collaboratives: improving the lives of both trainees and children
Authors: McDermott Helen , Vawda Hannah , Harvey Kate Christina , Lloyd Siwan , Course Christopher William , Broomfield Rebecca , Greenwood Annabel , Mason Timothy , Kirk Jeremy
Published: May 2019

Research is vital to paediatrics; however, many trainees feel there is a deficit in their opportunities, experience and exposure in this area. Three training regions in the UK, the West Midlands, Wales and Peninsula, have recently started region-wide, trainee-led research and governance collaboratives aimed at improving trainee access and education in research, undertaking good quality, multicentre audit, quality improvement and pilot projects in collaboration across the regions and implementing change. We report on the experiences, benefits and challenges of these trainee collaboratives (Paediatric Research Across the Midlands, Wales Research and Education Network and Peninsula Trainee Research Audit and Innovation Network) including a trainee survey looking at how these initiatives have improved skills in conducting multicentre prospective studies, team working skills, leadership, understanding of statistics and manuscripts and presentation skills. We also describe how collaboration with colleagues and participation in projects can benefit trainees in a wider sense of purpose and help to encourage morale, as well as what can be learnt as paediatric training moves forward.
Rationale and design of BERLIN VT study: a multicenter randomised trial comparing preventive versus deferred ablation of ventricular tachycardia
Authors: Tilz Roland Richard , Kuck Karl-Heinz , Kääb Stephan , Wegscheider Karl , Thiem Annette , Wenzel Beate , Willems Stephan , Steven Daniel
Published: May 2019

Introduction

Catheter ablation (CA) has shown to effectively reduce the burden of ventricular tachycardia in patients with implanted cardioverter-defibrillator (ICD). However, in patients with ICD implantation for secondary prevention of ventricular tachycardia (VT), the appropriate time point of CA and its effect on mortality and heart failure progression remains a matter of debate.

Methods and analysis

We present the design of the ongoing preventiveaBlation ofvEntriculartachycaRdia in patients with myocardiaLINfarction (BERLIN VT) study that aims to prospectively enrol 208 patients with a stable ischaemic cardiomyopathy, a left ventricular ejection fraction of 30% to 50% and documented ventricular tachycardia. Patients will be 1:1 randomised to undergo CA at the time of ICD implantation or CA after the third appropriate ICD shock for ventricular tachycardia. ICD implantation will be performed in all patients. The primary endpoint is defined as the time to first event comprising all-cause mortality and unplanned hospital admission for congestive heart failure or for symptomatic VT/ventricular fibrillation. The patients will be followed until study termination according to the event driven design. Completion of enrolment is expected for mid of 2019.

Ethics and dissemination

The study had been approved by the “Ethik-kommission der Landesärztekammer Hamburg” as well as the local institutional review boards for each of the participation sites. The results of the trial will be published in peer-reviewed journals

Trial registration number

NCT02501005.
Multifaceted intervention to enhance cognition in older people at risk of cognitive decline: study protocol for the Protein Omega-3 and Vitamin D Exercise Research (PONDER) study
Authors: Macpherson Helen , Brownell Sarah , Duckham Rachel L , Meyer Barbara , Mirzaee Sam , Daly Robin M
Published: May 2019

Introduction

An increasing number of people are living with cognitive impairment and dementia. Current pharmacological therapies at best reduce Alzheimer’s disease symptomatology but do not delay dementia onset in those at high risk. Structured exercise interventions can enhance cognition in older people; however, to produce long lasting, clinically relevant cognitive benefits, it is proposed that a multifaceted approach incorporating exercise with dietary supplements will address a wider range of mechanisms involved in cognitive decline. The Protein Omega-3 aNd vitamin D Exercise Research (PONDER) study aims to investigate the cognitive effects of a multimodal exercise programme combined with nutritional supplementation in older adults with subjective memory impairment (SMI).

Methods and analysis

The PONDER study is a single-centre, 12-month, community-based, parallel group, randomised, double-blind, placebo controlled trial involving a 6-month multifaceted intervention with a further 6-month follow-up. Participants will be 148 people from Melbourne, Australia, aged 60–85 years with SMI who will be randomised (1:1 ratio) to either a 6-month supervised multimodal exercise programme combined with omega-3 fatty acid, vitamin D and protein supplementation or a stretching/flexibility exercise programme combined with placebo supplements. The primary outcome is the change in cognition after 6 months as assessed by the Trail Making Test and global cognitive function assessed from the Cogstate Computerised battery. Secondary outcomes will include memory, working memory/learning and attention/psychomotor function, the Montreal Cognitive Assessment, mood, quality of life, muscle strength, physical function, body composition, cardiovascular health and sleep quality. Cognition at 12 months will represent a secondary outcome.

Ethics and dissemination

This study has been approved by the Deakin University Human Research Ethics Committee (project 2016–260). Informed consent will be obtained from all participants. The authors intend to submit the findings of the study to peer-reviewed journals or academic conferences to be published.

Trial registration number

ACTRN12616001549415; Pre-results.
Effects of expanding outpatient benefit package on the rationality of medical service utilisation of patients with hypertension: a quasi-experimental trial in rural China
Authors: He Ruibo , Miao Yudong , Zhang Liang , Yang Jian , Li Zhong , Li Boyang
Published: May 2019

Objective

To estimate the effects of expanding outpatient benefit package on ameliorating the issues of over-reliance on inpatient services and seeking higher level medical services in rural China.

Design

A quasi-experimental design.

Setting and participants

1673 pairs of patients with hypertension were selected after using propensity score matching from Dangyang county (intervention group) and Zhijiang (control group) county, Hubei province.

Intervention

The outpatient annual reimbursement capping line was expanding from ¥300 to ¥600, daily capping line from ¥10/12 to ¥150. The compensation scope and institution were also enlarged from January 2016.

Outcome measures

The difference-in-differences model was used to estimate the effects on medical service type selection. χ2test was used to verify the effects on medical institution selection. We also examined the effects on health outcomes through the length of stay and blood pressure changes.

Results

The intervention was associated with 3.225 times (p=0.001) increase in total visits. Outpatient visits increased by 3.3 times (p=0.008), whereas the township level presented a maximum increase of 1.932 times (p=0.001). The inpatient visits declined by 0.075 times (p=0.000), whereas county-level inpatient visits reached a maximum decrease of 0.042 times (p=0.033). Meanwhile, the township level exhibited a maximum proportion growth of 14.8% in outpatient (p=0.000) and 13.3% in inpatient visits (p=0.048). Outpatient visits at the county level dropped at 13.2% (p=0.000), whereas inpatients visits declined by 7.7% (p=0.040). The length of stay and blood pressure were decreased, respectively, compared with the control group.

Conclusion

Improving outpatient benefit package alleviated patient dependence on inpatient services through motivating outpatient service utilisation, consolidated the primacy of township health centres and guided patients to return to primary medical institutions. The health insurance reform should ‘take the long view’ in the future, and more attention should be paid to the rationality of medical service utilisation.
How people fit in at work: systematic review of the association between person–organisation and person–group fit with staff outcomes in healthcare
Authors: Herkes Jessica , Churruca Kate , Ellis Louise A , Pomare Chiara , Braithwaite Jeffrey
Published: May 2019

Objectives

People interact with their work environment through being, to a greater or lesser extent, compatible with aspects of their setting. This interaction between person and environment is particularly relevant in healthcare settings where compatibility affects not only the healthcare professionals, but also potentially the patient. One way to examine this association is to investigate person–organisation (P-O) fit and person–group (P-G) fit. This systematic review aimed to identify and synthesise knowledge on both P-O fit and P-G fit in healthcare to determine their association with staff outcomes. It was hypothesised that there would be a positive relationship between fit and staff outcomes, such that the experience of compatibility and ‘fitting in’ would be associated with better staff outcomes.

Design

A systematic review was conducted based on an extensive search strategy guided by Preferred Reporting Items for Systematic review and Meta-Analyses to identify relevant literature.

Data sources

CINAHL Complete, EMBASE, Ovid MEDLINE, PsycINFO and Scopus.

Eligibility criteria

Articles were included if they were empirical studies, published in peer-reviewed journals in English language, set in a healthcare context and addressed the association that staff outcomes have with P-O and/or P-G fit.

Data extraction and synthesis

Included texts were examined for study characteristics, fit constructs examined and types of staff outcomes assessed. The Quality Assessment Tool was used to assess risk of bias.

Results

Twenty-eight articles were included in the review. Of these, 96.4% (27/28) reported a significant, positive association between perception of fit and staff outcomes in healthcare contexts, such that a sense of compatibility had various positive implications for staff, including job satisfaction and retention.

Conclusion

Although the results, as with all systematic reviews, are prone to bias and definitional ambiguity, they are still informative. Generally, the evidence suggests an association between employees’ perceived compatibility with the workplace or organisation and a variety of staff outcomes in healthcare settings.
Scoping review on interventions to improve adherence to reporting guidelines in health research
Authors: Blanco David , Altman Doug , Moher David , Boutron Isabelle , Kirkham Jamie J , Cobo Erik
Published: May 2019

Objectives

The goal of this study is to identify, analyse and classify interventions to improve adherence to reporting guidelines in order to obtain a wide picture of how the problem of enhancing the completeness of reporting of biomedical literature has been tackled so far.

Design

Scoping review.

Search strategy

We searched the MEDLINE, EMBASE and Cochrane Library databases and conducted a grey literature search for (1) studies evaluating interventions to improve adherence to reporting guidelines in health research and (2) other types of references describing interventions that have been performed or suggested but never evaluated. The characteristics and effect of the evaluated interventions were analysed. Moreover, we explored the rationale of the interventions identified and determined the existing gaps in research on the evaluation of interventions to improve adherence to reporting guidelines.

Results

109 references containing 31 interventions (11 evaluated) were included. These were grouped into five categories: (1) training on the use of reporting guidelines, (2) improving understanding, (3) encouraging adherence, (4) checking adherence and providing feedback, and (5) involvement of experts. Additionally, we identified lack of evaluated interventions (1) on training on the use of reporting guidelines and improving their understanding, (2) at early stages of research and (3) after the final acceptance of the manuscript.

Conclusions

This scoping review identified a wide range of strategies to improve adherence to reporting guidelines that can be taken by different stakeholders. Additional research is needed to assess the effectiveness of many of these interventions.
Communication skills attitude scale: a translation and validation study in asample of registered nurses in Poland
Authors: Panczyk Mariusz , Iwanow Lucyna , Zarzeka Aleksander , Jaworski Mariusz , Gotlib Joanna
Published: May 2019

Objectives

To translate and validate the Communication Skills Attitude Scale in the Polish language (CSAS-P) and its adaptation for use among registered nurses.

Design

A cross-sectional descriptive design was used in order to translate and validate the CSAS-P. The following psychometric properties of CSAS-P were evaluated: content validity (content validity index), theoretical relevance (exploratory and confirmative factor analysis), one-dimensionality of subscales (principal component analysis), internal consistency (Cronbach’s α), test–retest reliability and discriminant validity.

Setting

Participants were identified and recruited from the Centre for Postgraduate Education for Nurses and Midwives in Warsaw, Poland.

Participants

The validation group comprised 2014 registered nurses who were undertaking a spring specialisation exam in 2017.

Results

The overall content validity index was >0.80, which was interpreted as indicating validity. The factor structure of CSAS-P differed from the original version, and removing three items from the scale better fit the data. The positive attitude subscale (11 items) and negative attitude subscale (12 items) were characterised by one-dimensionality and high internal consistency (Cronbach’s α=0.901 and 0.802, respectively). Test–retest analysis confirmed the stability of the measurement for both subscales and particular items. Nurses with prior participation in communication courses scored significantly higher than those without such education (p<0.05), confirming the discriminant validity of CSAS-P.

Conclusions

The psychometric properties of CSAS-P were comparable to the English language original. Further validation of CSAS-P in other groups of healthcare professionals may increase its applicability. CSAS-P can be used to evaluate attitudes towards learning communication skills among registered nurses.
Altering standard admission order sets to promote clinical laboratory stewardship: a cohort quality improvement study
Authors: Leis Benjamin , Frost Andrew , Bryce Rhonda , Lyon Andrew W , Coverett Kelly
Published: May 2019

Background

Careful design of preprinted order sets is needed to prevent medical overuse. Recent work suggests that removing a single checkbox from an order set changes physicians’ clinical decision-making.

Local problem

During a 2-month period, our coronary care unit (CCU) ordered almost eight times as many serum thyroid-stimulating hormone (TSH) tests as our neighbouring intensive care unit, many without a reasonable clinical basis. We postulated that we could reduce inappropriate testing and improve clinical laboratory stewardship by removing the TSH checkbox from the CCU admission order set.

Methods

After we retrospectively evaluated CCU TSH ordering before intervention, the checkbox was removed from the CCU admission order set. Twelve weeks later, we commenced a prospective 2-month assessment of TSH testing and clinical sequelae of thyroid disease among all CCU admissions. If clinical indications were absent or testing had occurred within 6 weeks, TSH requests were labelled as ‘inappropriate’.

Results

Physician ordering and, specifically, inappropriate ordering decreased substantially after the intervention. In 2016 among physician-ordered TSH tests, 60.6% (66/109) were inappropriate; in 2017 this decreased to 20% (2/10, p=0.01). Overall, the net effect of checkbox removal saw the decrease in TSH testing without clinical indication outweigh an increase in missed testing where indications appear to exist.

Conclusions

Provision of an optional checkbox for a laboratory test in an admission order set can promote overuse of laboratory resources. Simple removal of a checkbox may dramatically change test ordering patterns and promote clinical laboratory stewardship. Given our reliance on order sets, particularly by trainees, changes to order sets must be cautious to assure guideline-directed care is maintained.
Imminent death: clinician certainty and accuracy of prognostic predictions
Authors: White Nicola , Reid Fiona , Vickerstaff Victoria , Harries Priscilla , Tomlinson Christopher , Stone Patrick
Published: May 2019

Objectives

To determine the accuracy of predictions of dying at different cut-off thresholds and to acknowledge the extent of clinical uncertainty.

Design

Secondary analysis of data from a prospective cohort study.

Setting

An online prognostic test, accessible by eligible participants across the UK.

Participants

Eligible participants were members of the Association of Palliative Medicine. 99/166 completed the test (60%), resulting in 1980 estimates (99 participants × 20 summaries).

Main outcome measures

The probability of death occurring within 72 hours (0% certain survival−100% certain death) for 20 patient summaries. The estimates were analysed using five different thresholds: 50/50%, 40/60%, 30/70%, 20/80% and 10/90%, with percentage values between these extremes being regarded as ‘indeterminate’. The positive predictive value (PPV), negative predictive value (NPV) and the number of indeterminate cases were calculated for each cut-off.

Results

Using a <50% versus >50% threshold produced a PPV of 62%, an NPV of 74% and 5% indeterminate cases. When the threshold was changed to ≤10% vs ≥90%, the PPV and NPV increased to 75% and 88%, respectively, at the expense of an increase of indeterminate cases up to 62%.

Conclusion

When doctors assign a very high (≥90%) or very low (≤10%) probability of imminent death, their prognostic accuracy is improved; however, this increases the number of ‘indeterminate’ cases. This suggests that clinical predictions may continue to have a role for routine prognostication but that other approaches (such as the use of prognostic scores) may be required for those cases where doctors’ estimates are indeterminate.
CLIPPERS and its mimics: evaluation of new criteria for the diagnosis of CLIPPERS
Authors: Taieb Guillaume , Mulero Patricia , Psimaras Dimitri , van Oosten Bob W , Seebach Jörg D. , Marignier Romain , Pico Fernando , Rigau Valérie , Ueno Yuji , Duflos Claire , Fominykh Vera , Guiraud Vincent , Lebrun-Frénay Christine , Camdessanché Jean-Philippe , Kerschen Philippe , Ahle Guido , Téllez Nieves , Rovira Alex , Hoang-Xuan Khe , Pelletier Jean , Labauge Pierre
Published: May 2019

Objective

To evaluate the accuracy of the recently proposed diagnostic criteria for chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS).

Methods

We enrolled 42 patients with hindbrain punctate and/or linear enhancements (<3 mm in diameter) and tested the CLIPPERS criteria.

Results

After a median follow-up of 50 months (IQR 25–82), 13 out of 42 patients were CLIPPERS-mimics: systemic and central nervous system lymphomas (n=7), primary central nervous system angiitis (n=4) and autoimmune gliopathies (n=2). The sensitivity and specificity of the CLIPPERS criteria were 93% and 69%, respectively. Nodular enhancement (
≥
3 mm in diameter), considered as a red flag in CLIPPERS criteria, was present in 4 out of 13 CLIPPERS-mimics but also in 2 out of 29 patients with CLIPPERS, explaining the lack of sensitivity. Four out of 13 CLIPPERS-mimics who initially met the CLIPPERS criteria displayed red flags at the second attack with a median time of 5.5 months (min 3, max 18), explaining the lack of specificity. One of these four patients had antimyelin oligodendrocyte glycoprotein antibodies, and the three remaining patients relapsed despite a daily dose of prednisone/prednisolone
≥
30 mg and a biopsy targeting atypical enhancing lesions revealed a lymphoma.

Conclusions

Our study highlights that (1) nodular enhancement should be considered more as an unusual finding than a red flag excluding the diagnosis of CLIPPERS; (2) red flags may occur up to 18 months after disease onset; (3) as opposed to CLIPPERS-mimics, no relapse occurs when the daily dose of prednisone/prednisolone is
≥
30 mg; and (4) brain biopsy should target an atypical enhancing lesion when non-invasive investigations remain inconclusive.
Cardiogenic shock: evolving definitions and future directions in management
Authors: Jones Tara L , Nakamura Kenta , McCabe James M
Published: May 2019

Cardiogenic shock (CS) is a complex and highly morbid entity conceptualised as a vicious cycle of injury, cardiac and systemic decompensation, and further injury and decompensation. The pathophysiology of CS is incompletely understood but limited clinical trial experience suggests that early and robust support of the failing heart to allow for restoration of systemic homoeostasis appears critical for survival. We review the pathophysiology, clinical features and trial data to construct a contemporary model of CS as a systemic process characterised with maladaptive compensatory mechanisms requiring prompt and appropriately tailored medical and mechanical support for optimal outcomes. We conclude with an algorithmic approach to acute CS incorporating clinical and haemodynamic data to match the patient’s cardiac and systemic needs as a template for contemporary management.
Management of perioperative myocardial ischaemia after isolated coronary artery bypass graft surgery
Authors: Sef Davorin , Szavits-Nossan Janko , Predrijevac Mladen , Golubic Rajna , Sipic Tomislav , Stambuk Kresimir , korda zvonimir , Meier Pascal , turina Marko Ivan
Published: May 2019

Objectives

Updated knowledge about perioperative myocardial ischaemia (MI) after coronary artery bypass grafting (CABG) and treatment of acute graft failure is needed. We analysed main factors associated with perioperative MI and effects of immediate coronary angiography-based treatment strategy on patient outcome.

Methods

Among 1119 consecutive patients with coronary artery disease who underwent isolated CABG between January 2011 and December 2015, 43 (3.8%) patients underwent urgent coronary angiography due to suspected perioperative MI. All the data were prospectively collected and retrospectively analysed. The primary endpoint was 30-day mortality; postoperative left ventricular ejection fraction) and major adverse cardiac events were secondary endpoints.

Results

Overall, 30-day mortality in patients with CABG was 1.4% while in patients who developed perioperative MI was 9% (4 patients). Angiographic findings included incorrect graft anastomosis, graft spasm, dissection, acute coronary artery thrombotic occlusion and ischaemia due to incomplete revascularisation. Emergency reoperation (Redo) was performed in 14 (32%), acute percutaneous coronary intervention (PCI) in 15 (36%) and conservative treatment (Non-op) in 14 patients. Demographic and preoperative clinical characteristics between the groups were comparable. Postoperative LVEF was significantly reduced in the Redo group (45% post-op vs 53% pre-op) and did not change in groups PCI (56% post-op vs 57% pre-op) and Non-op (58% post-op vs 57% pre-op).

Conclusions

Urgent angiography allows identification of the various underlying causes of perioperative MI and urgent treatment when this is needed. Urgent PCI may be associated with improved clinical outcome in patients with early graft failure.
Biological variation of cardiac markers in patients with aortic valve stenosis
Authors: Peeters Frederique E C M , Kietselaer Bas L J H , Hilderink Judith , van der Linden Noreen , Niens Marijke , Crijns Harry J G M , Meex Steven J R
Published: May 2019

Objective

Cardiac biomarkers hold promise for follow-up and management of aortic valve stenosis (AVS). When interpreting serial biomarker measurements of patients with AVS, it can be challenging to distinguish ‘real changes’ from ‘random fluctuation’. Hence, robust estimation of the biological variation of these biomarkers is essential. In the present study we assessed biological variation of B-type natriuretic peptide (BNP), N-terminus pro-brain natriuretic peptide (NT-proBNP), high-sensitivity troponin-T and high-sensitivity troponin-I (hs-TnT and hs-TnI), and ST2 in subjects with stable AVS.

Methods

Serial blood sampling was performed in 25 subjects with moderate AVS—confirmed by echocardiography—and all free from acute cardiovascular events in the past 6 months. Blood samples were taken on seven standardised occasions during 1 year. Analytical variation (CVA), within-subject biological variation (CVI), between-subject biological variation (CVG), index of individuality (II) and reference change values were calculated for all cardiac biomarkers.

Results

CVIwas highest for BNP (62.0%, 95% CI 52.5 to 75.4) and lowest for hs-TnI (9.2%, 95% CI 2.8 to 13.8). CVGexceeded the CVIfor all biomarkers except BNP, and ranged from 19.8% (95% CI 13.8 to 33.4) for ST2 to 57.2% (95% CI 40.4 to 97.3) for hs-TnT. NT-proBNP, hs-TnT and ST2 revealed CVA<5%, while BNP and hs-TnI showed a higher CVA(19.7 and 14.9, respectively). All biomarkers except BNP showed marked individuality, with II ranging from 0.21 to 0.67 (BNP 1.34).

Conclusion

This study provides the first biological variation estimates of cardiac biomarkers in patients with stable AVS. These estimates allow a more evidence-based interpretation of biomarker changes in the follow-up and management of patients with AVS.

Trial registration number

NCT02510482
Characterisation of HIV-1 molecular transmission clusters among newly diagnosed individuals infected with non-B subtypes in Italy
Authors: Fabeni Lavinia , Alteri Claudia , Berno Giulia , Scutari Rossana , Orchi Nicoletta , De Carli Gabriella , Bertoli Ada , Carioti Luca , Gori Caterina , Forbici Federica , Salpini Romina , Vergori Alessandra , Gagliardini Roberta , Cicalini Stefania , Mondi Annalisa , Pinnetti Carmela , Mazzuti Laura , Turriziani Ombretta , Colafigli Manuela , Borghi Vanni , Montella Francesco , Pennica Alfredo , Lichtner Miriam , Girardi Enrico , Andreoni Massimo , Mussini Cristina , Antinori Andrea , Ceccherini-Silberstein Francesca , Perno Carlo Federico , Santoro Maria Mercedes
Published: May 2019

Objective

We evaluated the characteristics of HIV-1 molecular transmission clusters (MTCs) in 1890 newly diagnosed individuals infected with non-B subtypes between 2005 and 2017 in Italy.

Methods

Phylogenetic analyses were performed onpolsequences to characterise subtypes/circulating recombinant forms and identify MTCs. MTCs were divided into small (SMTCs, 2–3 sequences), medium (MMTCs, 4–9 sequences) and large (LMTCs, ≥10 sequences). Factors associated with MTCs were evaluated using logistic regression analysis.

Results

145 MTCs were identified and involved 666 individuals (35.2%); 319 of them (16.9%) were included in 13 LMTCs, 111 (5.9%) in 20 MMTCs and 236 (12.5%) in 112 SMTCs. Compared with individuals out of MTCs, individuals involved in MTCs were prevalently Italian (72.7% vs 30.9%, p<0.001), male (82.9% vs 62.3%, p<0.001) and men who have sex with men (MSM) (43.5% vs 14.5%, p<0.001). Individuals in MTCs were also younger (median (IQR) years: 41 (35–49) vs 43 (36–51), p<0.001) and had higher CD4 cell count in comparison with individuals out of MTCs (median (IQR): 109/L: 0.4 (0.265–0.587) vs 0.246 (0.082–0.417), p<0.001). The viral load remained stable between the two groups (median (IQR) log10copies/mL: 4.8 (4.2–5.5) vs 5.0 (4.3–5.5), p=0.87). Logistic regression confirmed that certain factors such as being MSM, of Italian origin, younger age and higher CD4 cell count were significantly associated with MTCs.

Conclusions

Our findings show that HIV-1 newly diagnosed individuals infected with non-B subtypes are involved in several MTCs in Italy. These MTCs include mainly Italians and MSM and highlight the complex phenomenon characterising the HIV-1 spread. This is important especially in view of monitoring the HIV epidemic and guiding the public health response.
The FMS-like tyrosine kinase-3 ligand/lung dendritic cell axis contributes to regulation of pulmonary fibrosis
Authors: Tort Tarrés Meritxell , Aschenbrenner Franziska , Maus Regina , Stolper Jennifer , Schuette Lisanne , Knudsen Lars , Lopez Rodriguez Elena , Jonigk Danny , Kühnel Mark Philipp , DeLuca David , Prasse Antje , Welte Tobias , Gauldie Jack , Kolb Martin RJ , Maus Ulrich A
Published: May 2019

Rationale

Dendritic cells (DC) accumulate in the lungs of patients with idiopathic lung fibrosis, but their pathogenetic relevance is poorly defined.

Objectives

To assess the role of the FMS-like tyrosine kinase-3 ligand (Flt3L)-lung dendritic cell axis in lung fibrosis.

Measurements and main results

We demonstrate in a model of adenoviral gene transfer of active TGF-β1 that established lung fibrosis was accompanied by elevated serum Flt3L levels and subsequent accumulation of CD11bposDC in the lungs of mice. Patients with idiopathic pulmonary fibrosis also demonstrated increased levels of Flt3L protein in serum and lung tissue and accumulation of lung DC in explant subpleural lung tissue specimen. Mice lacking Flt3L showed significantly reduced lung DC along with worsened lung fibrosis and reduced lung function relative to wild-type (WT) mice, which could be inhibited by administration of recombinant Flt3L. Moreover, therapeutic Flt3L increased numbers of CD11bposDC and improved lung fibrosis in WT mice exposed to AdTGF-β1. In this line, RNA-sequencing analysis of CD11bposDC revealed significantly enriched differentially expressed genes within extracellular matrix degrading enzyme and matrix metalloprotease gene clusters. In contrast, the CD103posDC subset did not appear to be involved in pulmonary fibrogenesis.

Conclusions

We show that Flt3L protein and numbers of lung DC are upregulated in mice and humans during pulmonary fibrogenesis, and increased mobilisation of lung CD11bposDC limits the severity of lung fibrosis in mice. The current study helps to inform the development of DC-based immunotherapy as a novel intervention against lung fibrosis in humans.
Threshold fines content and behavior of sands with nonplastic silts
Authors: Polito Carmine P. , Sibley Erin L.D.
Published: May 2019

The threshold fines content of a sand with nonplastic fines represents the silt content where the soil transitions from being a sand matrix, with silt particles entirely contained in the voids between the sands, to being a silt matrix that contains isolated sand grains. A laboratory testing program was performed on a series of mixtures of sand and silt, with silt contents ranging from 0% to 45%, to determine if the friction angle, cyclic resistance, and normalized dissipated energy per unit volume required to initiate liquefaction changed based upon the silt content of the soil relative to the threshold fines content. These data were evaluated with respect to whether the silt content of the specimens was below the lower-bound threshold fines content or above the upper-bound threshold fines content. It was determined that soils above the upper-bound threshold fines content had lower friction angles, lower cyclic resistances, and required less normalized dissipated energy per unit volume to initiate liquefaction than soils below the lower-bound threshold fines content. It was also shown that under the larger strains experienced during monotonic testing, the friction angle did not reach a constant value until it was well above the upper-bound limiting silt content.
Effects of nucleotide supplementation to corn–soybean meal-based diet on growth performance, fecal microflora, and blood profiles of sows and performance of suckling piglets
Authors: Jiao Y. , Upadhaya S.D. , Kim I.H.
Published: May 2019

A total of 45 sows (Landrace × Yorkshire) and their litters were used in this study to evaluate the efficacy of nucleotide supplementation on reproductive performance, growth performance, fecal microflora, and blood profiles in sows and piglets. Sows were allocated to one of three treatments (15 pigs per treatment and the average parity was 4.13). Dietary treatments consisted of (1) CON: basal diet, (2) T1: CON + 0.5% nucleotides, and (3) T2: CON + 1.0% nucleotides. In this study, the average daily feed intake during lactation and back fat at weaning day was increased linearly (P < 0.05) in sows with the increase in nucleotide supplementation levels. Sows receiving increasing levels of nucleotides had linearly increased fecal Lactobacillus counts and decreased Escherichia coli counts at weaning day (P < 0.05). Linear reduction of the epinephrine, norepinephrine, and cortisol in sows was observed at weaning day, whereas superoxide dismutase was increased linearly (P < 0.05). Body weight and average daily gain in piglets were linearly (P < 0.05) increased with the increasing levels of nucleotides. Linear increase (P < 0.05) was also observed on total piglets born, live piglets, and piglet survival. The current study demonstrated the importance of nucleotides in the diets of sows to improve sow and piglet performance.
CRISPR-Cas9 knockout ofqseBinduced asynchrony between motility and biofilm formation inEscherichia coli
Authors: Gou Yi , Liu Weiqi , Wang Jing Jing , Tan Ling , Hong Bin , Guo Linxia , Liu Haiquan , Pan Yingjie , Zhao Yong
Published: May 2019

Generally, cell motility and biofilm formation are tightly regulated. The QseBC two-component system (TCS) serves as a bridge for bacterial signal transmission, in which the protein QseB acts as a response regulator bacterial motility, biofilm formation, and virulence. The mechanisms that govern the interaction between QseBC and their functions have been studied in general, but the regulatory role of QseB on bacterial motility and biofilm formation is unknown. In this study, the CRISPR-Cas9 system was used to construct the Escherichia coli MG1655ΔqseB strain (strain ΔqseB), and the effects of the qseB gene on changes in motility and biofilm formation in the wild type (WT) were determined. The motility assay results showed that the ΔqseB strain had higher (p < 0.05) motility than the WT strain. However, there was no difference in the formation of biofilm between the ΔqseB and WT strains. Real-time quantitative PCR illustrated that deletion of qseB in the WT strain downregulated expression of the type I pili gene fimA. Therefore, we might conclude that the ΔqseB induced the downregulation of fimA, which led to asynchrony between motility and biofilm formation in E. coli, providing new insight into the functional importance of QseB in regulating cell motility and biofilm formation.