bluuebunny/crossref_metadata_2025 huggingface dataset:
Model to Predict the Effect of Through-Thickness Loading on Ply Cracking in General Symmetric Laminates
Authors: McCartney L. N.
Published: January 2022

For the case of the combined in-plane biaxial and shear loading of a general symmetric laminate having ply cracks in a single orientation, a stress transfer model has been developed that can predict the stress and displacement distributions at all points in the laminate provided that generalised plane strain conditions prevail, as expected in such laminates in regions away from free edges. For the special case of cross-ply laminates, the modelling of the effects of a uniform through-thickness loading has led to an extensive set of inter-relationships between the thermo-elastic constants, whose validity has been verified by solutions to the stress transfer model. These interrelationships have been used to develop a very simple crack formation criterion that involves a scalar effective stress that is able to take account of the general in-plane loading of the laminate. The paper will investigate the extension of these results to general symmetric laminates with ply cracks subject to a uniform through-thickness load combined with general in-plane loading involving both biaxial and shear stresses.

The paper will describe the assumptions on which the model is based, and the representation for the stress and displacement field that has been shown to be consistent with the Reissner variational principle whose application to composites has been pioneered by Pagano. Following Pagano, ply refinement techniques will be used to improve the accuracy of predictions, and indicate the nature of the singularity that exists at the tips of the ply cracks. The model will be used to predict the dependence of the thermoelastic constants on crack density, and to investigate the validity of new inter-relationships between the predicted constants. The inter-relationships will be used to develop a relatively simple crack formation criterion that generalises the known cross-ply criterion to the important case of general symmetric laminates.

Evidence will be presented showing how the new model has been validated by comparison of predictions with finite element analysis for cracked laminates (e.g. quasi-isotropic laminates), and with experimental data.
Failure Prediction of Bonded Joints of Composite Engineering Structures
Authors: Bogdanovich Alexander E. , Yushanov Sergei P.
Published: January 2022

First part of the paper presents brief review of fracture mechanics applications to progressive failure prediction in adhesive bonded joints under mechanical loading end environmental effects (temperature and moisture) typical for the aircraft and civil engineering structures. Existing concepts of critical energy release rates and critical stress intensity factors for fracture modes I and II are evaluated in the context of failure and durability of adhesive bonded joints. The challenging problem of reliable experimental fracture toughness characterization of bonded laminated composites is emphasized.

Second part of the paper presents novel development of 3-D variational analysis aimed at predicting crack propagation in adhesive composite bonded joints exposed to mechanical loading combined with variable temperature and moisture. A general 3-D variational thermo-hygro-mechanical approach is developed, based on the principle of minimum total potential energy. A brick-type composite mosaic model is allowing to incorporate the material property variation in all three coordinate directions. The displacement field in each of the bricks is approximated in terms of triple series with Bernstein basis functions of an arbitrary degree used in all the coordinate directions. In the case of no pre-existing cracks, all of the bricks are perfectly bonded through the displacement continuity conditions. If there is a 2-D surface crack perpendicular to one of the coordinate axes (the crack can be arbitrarily located inside the structure, including any part of the interfaces or bondlines), then the respective displacement continuity conditions are released along the corresponding surface area. A progressive failure analysis approach is then developed using the energy release rates evaluated for various possible scenarios of a cohesive, adhesive or interlaminar crack propagation. Several cracks of the same type or different types can be analyzed simultaneously.

Numerical examples illustrate application of the developed analysis approach to double-lap adhesive bonded joints with cross-ply laminated composite adherends under some typical thermomechanical loading cases. The moisture effect is incorporated through the time-dependent critical energy release rates for Modes I and II. Several pre-existing cracks are introduced (separately or conjointly), and their propagation is followed using the computed strain energy release rates around the crack tip. Importantly, each of the distinct failure modes (adhesive, cohesive or interlaminar) is characterized by its specific critical strain energy release rate sensitive to the penetrating moisture. Numerical results and their comparison with available experimental data show that the developed analysis approach is capable of predicting the paths of dominating failure modes in adhesively bonded laminated composite joints.
Applications of Composite Grid Structures
Authors: Tsai Stephen W.
Published: January 2022

Composite grids have been exploited by users in the US, USSR, Japan, Germany, South Africa and no doubt others over the last twenty years. Most efforts suffered lack of manufacturing processes suitable for mass production. Our attempts during the last few years have produced several grid forms that show promise for commercialization. These processes are fundamentally different from the conventional laminated or woven structures currently in use.
Fabrication, Testing and Analysis of Composite Sandwich Structures
Authors: Daniel Isaac M. , Abot R. A. Jandro
Published: January 2022

The objective of this work was to study the behavior of composite sandwich structures and develop simple models to explain this behavior as a function of material, geometric and loading parameters. The scope of the study consists of mechanical characterization of the sandwich constituent materials, i. e., composite facings, honeycomb or foam cores, and adhesive layers; fabrication and testing of sandwich beams in pure bending; identification and recording of failure mechanisms by direct observation and nondestructive evaluation; and comparison of observed deformation and failure behavior with analytical predictions. Sandwich beams were fabricated by bonding carbon/epoxy (AS4/3501-6) facings to an aluminum honeycomb core with FM 73 film adhesive. Special techniques were developed to prevent premature failures under the loads and in the core and to insure failure in the test section under pure bending. Strains to failure in the facings were recorded with strain gages, and beam deflections and core strains were recorded with Moire techniques. The beam facings displayed characteristic nonlinearities for the composite material used, a softening nonlinearity on the compression side and a stiffening one on the tension side. These nonlinearities appear more pronounced than in the case of monotonic axial loadings of the composite material alone. The linear response of the beam is perfectly described by a simple bending model neglecting the contribution of the core, however, the more pronounced nonlinear behavior requires more accurate characterization of the core and adhesive materials separately, and more refined modeling.
Cracking of Plates With Randomly Distributed Holes by a Maximum Entropy Method
Authors: Ostoja-Starzewski M. , Al-Ostaz Ahmed , Jasiuk I.
Published: January 2022

It has recently been shown [1] that fracture response of nominally identical elastic-brittle (epoxy) as well as ductile (aluminum) sheets, each containing randomly distributed circular holes, is non-unique. This non-uniqueness pertains, in particular, to the resulting fracture patterns and effective stress-strain curves, whereby both of these characteristics display considerable scatter. This result points to the significant influence which microscale random noise in material parameters may have on the global, macroscopic behavior. In this paper we formulate, on the basis of a maximum entropy method [2], a stochastic fracture mechanics model for this class of problems. The method is based on the statistics of experimental data, obtained for a number of specimens, involving the inter-hole crack lengths and their angles. It allows prediction of probability distributions of damage responses and patterns of Gibbs ensembles of random hole systems such as, for example, porous materials with millions of voids.
Numerical Study of Damage Growth in Particulate Composites
Authors: Kwon Y. W. , Liu C. T.
Published: January 2022

A numerical study was conducted to simulate and predict damage initiation and growth around the crack tip in particulate composite specimens made of hard particles embedded in a soft rubber-like matrix material. Therefore, damage evolution in the matrix material around crack tips was investigated. The progressive damage was modelded using a micro/macro-approach which combined two levels of analyses like the micro-level and the macro-level analyses. Damage description was undertaken at the microlevel using a simplified three-dimensional unit-cell model and an isotropic continuum damage theory. The numerical study examined both thin and thick specimens with a short or long edge crack to understand the effects of specimen thickness and crack size on the damage initiation, growth, and saturation. Some numerical results were validated by experimental data.
An Information System for Damage Tolerance of Polymer Matrix Composites
Authors: Turkgenc Ozgur , Dianati Reza , Mitrovic Milan , Hahn H. Thomas , Shypyrkevich Peter
Published: January 2022

Much research has been conducted to understand the damage tolerance behavior of polymer matrix composites. As a result, a fair amount of data is available together with a number of analytical models. However, there are so many parameters involved that the development of a generic model is rather difficult. The present paper proposes a decision support system, which can overcome such difficulty. In the information system, a list of possible parameters is generated and used as input. The output contains compression strength after impact, dent depth and damage area as well as literature references, raw data, tables, and plots. The information system is constituted in a relational database environment and expert system technology is incorporated so that low confidence input can be captured in order to report best matching cases. Parametric studies are also made available to determine the effect of each design parameter on the damage tolerance behavior. Case examples are included to demonstrate the practical use of the software for both data retrieval and similarity studies.
Spectral Analysis of Musical Notes as a Source of Information About Musical Instruments
Authors: Voronkin Oleksii
Published: January 2022

The integration of physics, music, and mathematics has long been used to increase students’ interest and motivation in these subjects. For example, previous articles in this journal have shown how to teach physical concepts in a musical context, use a smartphone to check the resonant frequencies of whistles, use a smartphone to examine the spectra of sounds, and apply Fourier analysis to the study of musical intervals. This article is devoted to the audio recordings analysis of saxophone sounds, violin, guitar, piano, hand bell, and ocarina in the Audacity editor. The purpose of this analysis is to determine the amplitude-frequency structures of musical notes and obtain information for the classroom about the physical characteristics of musical instruments and some playing techniques.
Dynamic Applets for Teaching Physics
Authors: Lingefjärd Thomas , Ahmet Guner
Published: January 2022

The subject of mathematics is important for many other subjects, including physics. The questions we ask in physics often need a mathematical translation to be graphically interpreted and transformed. Students learn physics when interacting with physical questions; questions from physics also give insights and discoveries in mathematical problems. In physics we often deal with questions that benefit from being illustrated with mathematical tools. A scientific theory (in physics or in another science) is an isomorphism between physical reality and a mathematical model.
How to Use the Archimedes Paradox for Educational Purposes
Authors: Noxaïc Armand Le , Fadel Kamil
Published: January 2022

The statics of fluids may seem simple at first but often poses problems for students when it comes to applying it to concrete cases. Despite its relatively simple laws, some subtleties, mainly related to the elastic characteristics of a fluid, must be noted. This elasticity allows the pressure exerted in a part of the fluid to propagate in its entirety, a non-intuitive concept for students as they consider more readily solid objects.
A Physics Story: Literacy technique for learning the language of physics
Authors: Lincoln James
Published: January 2022

Illustrations provided by Daniel Murrell , dansmurrell@gmail.com

When I began teaching high school physics, I found that many of my students were not just struggling with the mathematics of physics but the way the language was used. Physics is sometimes discussed as being a second language where common words are coded with specific alternate definitions (consider how you use the word “delta”). Furthermore, many of our students are English Language Learners. Thus, providing developmentally appropriate assistance to building scientific vocabulary not only addresses equity issues but can be a highly effective teaching strategy. In this article, I provide an example of one such approach to addressing literacy issues: a vocabulary building story on Convection, Conduction, and Radiation.
Talking Is Thinking: Supporting Student Sense-Making Through Discourse and Assessment
Authors: Jackson Whitney , Simpson Lauren A. , Whitworth Brooke A.
Published: January 2022

Learning in the classroom is highly influenced by the experiences a teacher plans for students. Concerned that students were not achieving adequate conceptual knowledge during traditional undergraduate physics courses, the authors used the Making Sense of SCIENCE curriculum to tailor a course for 21 pre-service elementary teachers at the University of Mississippi. The organization of instruction, facilitation practices, discussion opportunities, and assessment of content are all important aspects of the learning process. We found the changes we implemented significantly impacted the learning of students enrolled in this course.
A Quantitative Experiment of Liquid Dispersion Using Merely a Partially Submerged Mirror and Sunlight
Authors: Cordeiro Cristiano M. B. , Fujiwara Eric
Published: January 2022

The refractive index (RI) is probably the single most important parameter in optical systems. Chromatic dispersion, on the other hand, indicates how the RI depends on the wavelength and is central in, e.g., optical communication systems. Chromatic dispersion also plays an important role when teaching optics due to the captivating natural phenomenon of the rainbow and the white light decomposition with a prism. In this work, we propose and explore a method to characterize the refractive index of transparent liquids in the visible range without any dedicated equipment or device (such as prisms, goniometer, laser, detector, etc.).
Beyond the Classroom: Profiling Muon Flux in Relation to Overburden in Fermilab’s MINOS Tunnel
Authors: Winkler Eleanor Anne , Graham Paul , Unterman Nathan A. , Grey Benjamin , Miller Jacob M. , Miller Max J. , Sears Allen J. , Bernat Alex , Frank Shoshana , Simon Joshua , Eliaser Shira K. , Blackmore Tom , Copeland Emmanuelle , Senser Marybeth , Seiden Henry , Valsamis Anthony , Adams Mark
Published: January 2022

With support from QuarkNet, high school students investigated the effect of overburden on muon flux by collecting data from Fermilab’s Main Injector Neutrino Oscillation Search (MINOS) tunnel. Muon flux varied due to a change in overburden created by a 103-meter deep access shaft. A profile of muon flux as a function of distance from the access shaft was measured by observing muon flux from different locations within the tunnel.
Measuring the Speed of Earth Around the Sun Using a Classroom-Built Radio Horn Telescope
Authors: Herman Thaddeus
Published: January 2022

Even though many physics teachers take their students on a calculation adventure through circular motion and Newton’s universal law of gravity to determine Earth’s velocity, most of us leave it at that. We present the final result and say, “Look, Earth is moving around the Sun at about 107,000 km/hr (66,000 mph), yet we can’t feel the motion at all!” Well, thanks to an NSF-funded Research Experience for Teachers, some eager participants, a simply built radio horn telescope pointed at the center of the Milky Way, and the addition of Doppler effect considerations, we can verify our calculations through observation… science!
Wave-field representations with Green's functions, propagator matrices, and Marchenko-type focusing functions
Authors: Wapenaar Kees
Published: January 2022

Classical acoustic wave-field representations consist of volume and boundary integrals, of which the integrands contain specific combinations of Green's functions, source distributions, and wave fields. Using a unified matrix-vector wave equation for different wave phenomena, these representations can be reformulated in terms of Green's matrices, source vectors, and wave-field vectors. The matrix-vector formalism also allows the formulation of representations in which propagator matrices replace the Green's matrices. These propagator matrices, in turn, can be expressed in terms of Marchenko-type focusing functions. An advantage of the representations with propagator matrices and focusing functions is that the boundary integrals in these representations are limited to a single open boundary. This makes these representations a suitable basis for developing advanced inverse scattering, imaging and monitoring methods for wave fields acquired on a single boundary.
Effects of design and coupling parameters on the performance of electromagnetic transducers in round-window stimulation
Authors: Zhao Yu , Liu Houguang , Yang Jianhua , Yang Shanguo , Liu Wen , Huang Xinsheng
Published: January 2022

Many studies have investigated factors contributing to large variations in the outcomes of round-window (RW) stimulation but most have focused on the floating mass transducer (FMT). To determine whether results for the FMT hold for a fixed-type transducer (FTT), this study constructs two coupled finite element models of the transducer and the human ear that incorporate the cochlear third windows and inner structures of these two electromagnetic transducers. We use these FE models of the human ear and transducers to investigate the influence of four design parameters and coupling conditions for the transducers, i.e., the support's Young's modulus, the coupling layer's cross sectional area and Young's modulus, and the transducer's cross sectional area. The results show that an increase in the support's Young's modulus reduces the output of the FMT but increases that of the FTT. Reducing the cross sectional area and Young's modulus of the coupling layer significantly increases the low-frequency response of the FMT but slightly reduces that of the FTT. Reducing the cross sectional area of the transducer increases the output of the FMT but reduces that of the FTT. This shows that inner structures of electromagnetic transducers should be considered in the optimal design parameters and coupling conditions for RW stimulation.
Perception of temporally contrasted Japanese words by Spanish-English bilinguals and American English monolinguals
Authors: Hisagi Miwako , Zandona Mike , Kent Justin , Higby Eve
Published: January 2022

Japanese and English use temporal cues within vowels, suggesting an audio-processing advantage for temporally-cued contrasts, while Spanish does not. Using a categorial AXB discrimination task, this study investigated how American English-speaking monolinguals and early and late Spanish-English bilinguals perceive three types of temporally-contrasting Japanese pairs: vowel length (kado/kaado), consonant length (iken/ikken), and syllable number (hjaku/hijaku). All groups performed worse than Japanese controls for the vowel length and syllable number contrasts, but only early bilinguals differed from controls for consonant length. This research contributes to a better understanding of how the first-learned language influences speech perception in a second language.
Phonological and semantic similarity of misperceived words in babble: Effects of sentence context, age, and hearing loss
Authors: Vickery Blythe , Fogerty Daniel , Dubno Judy R.
Published: January 2022

This study investigated how age and hearing loss influence the misperceptions made when listening to sentences in babble. Open-set responses to final words in sentences with low and high context were analyzed for younger adults with normal hearing and older adults with normal or impaired hearing. All groups performed similarly in overall accuracy but differed in error type. Misperceptions for all groups were analyzed according to phonological and semantic properties. Comparisons between groups indicated that misperceptions for older adults were more influenced by phonological factors. Furthermore, older adults with hearing loss omitted more responses. Overall, across all groups, results suggest that phonological confusions most explain misperceptions in low context sentences. In high context sentences, the meaningful sentence context appears to provide predictive cues that reduce misperceptions. When misperceptions do occur, responses tend to have greater semantic similarity and lesser phonological similarity to the target, compared to low context sentences. In this way, semantic similarity may index a postdictive process by which ambiguities due to phonological confusions are resolved to conform to the semantic context of the sentence. These patterns demonstrate that context, age, and hearing loss affect the misperceptions, and potential sentence interpretation, made when listening to sentences in babble.
Generalization of Participation in Fitness Activities From Physical Education to Lunch Recess by Gender and Skill Level
Authors: Iserbyt Peter , van der Mars Hans , Drijvers Hannelore , Seghers Jan
Published: January 2022

Purpose: Comprehensive School Physical Activity Programs aim to maximize the application of skills learned in physical education (PE) in other settings. We investigated students’ generalization of participation in fitness activities from PE to organized fitness programs during lunch recess. Method: Voluntary participation of 153 (74 girls, age 12.4 years) students from five schools in a fitness recess program before, during, and after a 12-lesson sport education fitness season in PE was assessed by gender and skill level. Moderate to vigorous physical activity was assessed through systematic observation. Results: After the sport education season, participation in fitness recess dropped from 41% to 9%, p < .001, effect size = 0.34. Average moderate to vigorous physical activity was higher in fitness (45%) compared with traditional recess (11%), p < .001, effect size = 0.50, irrespective of gender and skill level. Discussion/Conclusion: Generalization of participation in fitness activities from PE to lunch recess is a promising strategy to increase students’ moderate to vigorous physical activity.
“Californian ‘Start-’Em-Young’ System”: The Golden State and US Swimming, 1954–1964
Authors: Hodler Matthew R. , Smith Maureen
Published: January 2022

Each Olympics, the American swimming team is comprised of swimmers from universities and club teams from across the country. California has produced elite swimmers since the first Olympics where US swimmers won a medal (1904), and its clubs and teams developed into national and international swimming powers in the post-World War II rejuvenation of the Olympics. This article investigates the ways the California Age Group swimming program shaped the American swimming culture as it rose to prominence in global competitions in the 1950s and 1960s, identifying the aquatic enterprise as an early iteration of youth sport as a serious, commercialized, and commodified pastime. Additionally, we explore how California Age Group swimming served as a site for young girls (and boys) to be a part of the American nationalist project in the post-war pre-Title IX era, an era when there were otherwise few sporting opportunities for girls.
A Rabbit Model to Study Antibiotic Penetration at the Site of Infection for Nontuberculous Mycobacterial Lung Disease: Macrolide Case Study
Authors: Kaya Firat , Ernest Jacqueline P. , LoMauro Katherine , Gengenbacher Martin , Madani Abdeldjalil , Aragaw Wassihun Wedajo , Zimmerman Matthew D. , Sarathy Jansy P. , Alvarez Nadine , Daudelin Isaac , Wang Han , Lanni Faye , Weiner Danielle M. , Via Laura E. , Barry Clifton E. , Olivier Kenneth N. , Dick Thomas , Podell Brendan K. , Savic Radojka M. , Dartois Véronique
Published: January 2022

Nontuberculous mycobacterial pulmonary disease (NTM-PD) is a potentially fatal infectious disease requiring long treatment duration with multiple antibiotics and against which there is no reliable cure. Among the factors that have hampered the development of adequate drug regimens is the lack of an animal model that reproduces the NTM lung pathology required for studying antibiotic penetration and efficacy.
Streptococcus gordonii
-Induced miRNAs Regulate CCL20 Responses in Human Oral Epithelial Cells
Authors: Tubero Euzebio Alves Vanessa , Al-Attar Ahmad , Alimova Yelena , Maynard Marshall H. , Kirakodu Sreenatha , Martinez-Porras Andrés , Hawk Gregory S. , Ebersole Jeffrey L. , Stamm Stefan , Gonzalez Octavio A.
Published: January 2022

The mechanisms through which oral commensal bacteria mitigates uncontrolled inflammatory responses of the oral mucosa remain unknown. Here, we show that representative oral bacterial species normally associated with oral health [
S. gordonii
(
Sg
),
V. parvula
(
Vp
), A. naeslundii (
An
),
C. sputigena
(
Cs
), and
N. mucosa
(
Nm
)] enhanced differential chemokine responses in oral epithelial cells (OECs), with some bacteria (
An, Vp, and Nm
) inducing higher chemokine levels (CXCL1, CXCL8) than others (
Sg, Cs
).
Correlation of ganglion cell complex thinning with baseline deep and superficial macular vessel density in glaucoma
Authors: Wu Jo-Hsuan , Moghimi Sasan , Nishida Takashi , Proudfoot James A , Kamalipour Alireza , Zangwill Linda M , Weinreb Robert N
Published: January 2022

Background/aims

To investigate the relationship between ganglion cell complex (GCC) thinning and baseline deep and superficial macular vessel density (VD) in glaucoma.

Methods

97 eyes of 69 primary open-angle glaucoma (POAG) and glaucoma suspect patients from the Diagnostics Innovations in Glaucoma Study with a minimum of 4 visits and 2 years of follow-up after baseline optical coherence tomography angiography (OCTA) examination were included. OCTA 3×3 mm2macular scans were acquired at each visit and used to calculate superficial and deep parafoveal VD (pfVD) and OCT-based parafoveal GCC (pfGCC) thickness. Association of baseline superficial and deep pfVD with pfGCC thinning rate was evaluated using linear mixed model.

Results

The included subjects had a baseline mean visual field mean deviation (95% CI) of −2.9 (–3.7 to –2.1) dB and a mean follow-up period of 3.6 years. In the univariable model, lower baseline superficial pfVD and higher mean intraocular pressure (IOP) during follow-up were significantly associated with a faster pfGCC thinning rate (p<0.05 for all), while deep pfVD was not (p=0.177). In the multivariable model, faster pfGCC thinning was correlated with higher mean IOP during follow-up (β=−0.05, p=0.002) and lower baseline superficial pfVD (β=−0.04, p=0.011). Eyes with a baseline superficial pfVD in the lowest tertile (≤46%) had significantly faster pfGCC loss compared with eyes with baseline superficial pfVD greater than 46% (p=0.015).

Conclusion

Lower baseline superficial pfVD, but not deep pfVD, was associated with faster pfGCC thinning in glaucoma. Moreover, superficial macular VD may help predict central macula thinning in patients with glaucoma.
Ambulatory care management of 69 patients with acute severe ulcerative colitis in comparison to 695 inpatients: insights from a multicentre UK cohort study
Authors: Sebastian Shaji , Patel Kamal V , Segal Jonathan P , Subramanian Sreedhar , Conley Thomas Edward , Gonzalez Haidee Aleman , Kent Alexandra J , Saifuddin Aamir , Hicks Lucy , Mehta Shameer , Bhala Neeraj , Brookes Matthew J , Lamb Christopher A , Kennedy Nicholas A ,   PROTECT ASUC collaborators, Walker Gareth J
Published: January 2022

Introduction

Acute severe ulcerative colitis (ASUC) traditionally requires inpatient hospital management for intravenous therapies and/or colectomy. Ambulatory ASUC care has not yet been evaluated in large cohorts.

Aims

We used data from PROTECT, a UK multicentre observational COVID-19 inflammatory bowel disease study, to report the extent, safety and effectiveness of ASUC ambulatory pathways.

Methods

Adults (≥18 years old) meeting Truelove and Witts criteria between 1 January 2019–1 June 2019 and 1 March 2020–30 June 2020 were recruited to PROTECT. We used demographic, disease phenotype, treatment outcomes and 3-month follow-up data. Primary outcome was rate of colectomy during the index ASUC episode. Secondary outcomes included corticosteroid response, time to and rate of rescue or primary induction therapy, response to rescue or primary induction therapy, time to colectomy, mortality, duration of inpatient treatment and hospital readmission and colectomy within 3 months of index flare. We compared outcomes in three cohorts: (1) patients treated entirely in inpatient setting; ambulatory patients subdivided into; (2) patients managed as ambulatory from diagnosis and (3) patients hospitalised and subsequently discharged to ambulatory care for continued intravenous steroids.

Results

37% (22/60) participating hospitals used ambulatory pathways. Of 764 eligible patients, 695 (91%) patients received entirely inpatient care, 15 (2%) patients were managed as ambulatory from diagnosis and 54 (7%) patients were discharged to ambulatory pathways. Aside from younger age in patients treated as ambulatory from diagnosis, no significant differences in disease or patient phenotype were observed. The rate of colectomy (15.0% (104/695) vs 13.3% (2/15) vs 13.0% (7/54), respectively, p=0.96) and secondary outcomes were similar among all three cohorts. Stool culture and flexible sigmoidoscopy were less frequently performed in ambulatory cohorts. Forty per cent of patients treated as ambulatory from diagnosis required subsequent hospital admission.

Conclusions

In a post hoc analysis of one of the largest ASUC cohorts collected to date, we report an emerging UK ambulatory practice which challenges treatment paradigms. However, our analysis remains underpowered to detect key outcome measures and further studies exploring clinical and cost-effectiveness as well as patient and physician acceptability are needed.

Trial registration number

NCT04411784.
Progression to severe visual impairment and blindness in POAG patients: pace and risk factors—a cohort study using German health claims data
Authors: Nestler Sophia , Kreft Daniel , Doblhammer Gabriele , Guthoff Rudolf F , Frech Stefanie
Published: January 2022

Objective

Glaucoma is a leading cause of severe visual impairment and blindness (SVI/B) worldwide. Hence, it is of utmost importance to explore relevant risk factors and study the pace of progression to SVI/B.

Methods and analysis

We used a random sample of 250 000 persons from administrative individual-level health records of the Allgemeine Ortskrankenkassen between 2004 and 2015. We identified 3535 primary open-angle glaucoma (POAG) patients aged 55 and older and followed them for up to 10 years. Monocular and binocular SVI/B were defined by the ICD-10 classifications H54.0 and H54.4. Ophthalmological and chronic disease risk factors were analysed by applying a multivariable Cox proportional hazard model.

Results

The risk of SVI/B in POAG patients was significantly increased by the presence of specific additional eye diseases such as secondary glaucoma (HR: 3.08, p<0.001), retinal vascular occlusion (HR: 3.00, p<0.001) or age-related macular degeneration (AMD) (HR: 2.26, p<0.001). The risk was highest in the first 2 years after the POAG diagnosis and significantly decreased after the fifth year (HR: 0.36, p=0.002). Ocular injuries, other ocular diseases, non-ophthalmological comorbidities, and age and sex had no significant influence (p>0.05).

Conclusion

Although progression to SVI/B is relatively rare in POAG patients in Germany, one must be aware of additional risk factors, such as secondary glaucoma, retinal vascular occlusion and AMD. Regular ophthalmological examinations help prevent the progression of SVI/B, especially in the first years after the POAG diagnosis. Specific, targeted, and timely treatments for the other eye diseases could help prevent or delay SVI/B.
Improving annual albuminuria testing for individuals with diabetes
Authors: Kam Sharon , Angaramo Santiago , Antoun Jacqueline , Bhatta Manasa R , Bonds Pauleatha Diggs , Cadar Adrian G , Chukwuma Valentine U , Donegan Patrick J , Feldman Zachary , Grusky Alan Z , Gupta Veerain K , Hatcher Jeremy B , Lee Jaclyn , Morales Natalia G , Vrana Erin N , Wessinger Bronson C , Zhang Michael Z , Fowler Michael J , Hendrickson Chase D
Published: January 2022

Background

Annual albuminuria screening detects the early stages of nephropathy in individuals with diabetes. Because early detection of albuminuria allows for interventions that lower the risk of developing chronic kidney disease, guidelines recommend annual testing for all individuals with type 2 diabetes mellitus and for those with type 1 diabetes for at least 5 years. However, at the Eskind Diabetes Clinic at the Vanderbilt University Medical Center, testing occurred less frequently than desired.

Methods

A quality improvement team first analysed the clinic’s processes, identifying the lack of a systematic approach to testing as the likely cause for the low rate. The team then implemented two successive interventions in a pilot of patients seen by nurse practitioners in the clinic. In the first intervention, staff used a dashboard within the electronic health record while triaging each patient, pending an albuminuria order if testing had not been done within the past year. In the second intervention, clinic leadership sent daily reminders to the triage staff. A statistical process control chart tracked monthly testing rates.

Results

After 6 months, annual albuminuria testing increased from a baseline of 69% to 82%, with multiple special-cause signals in the control chart.

Conclusions

This project demonstrates that a series of simple interventions can significantly impact annual albuminuria testing. This project’s success likely hinged on using an existing workflow to systematically determine if a patient was due for testing and prompting the provider to sign a pended order for an albuminuria test. Other diabetes/endocrinology and primary care clinics can likely implement a similar process and so improve testing rates in other settings. When coupled with appropriate interventions to reduce the development of chronic kidney disease, such interventions would improve patient outcomes, in addition to better adhering to an established quality metric.
System approach to prevent lost studies and improve radiology report turnaround time
Authors: Schick Jacob , Petscavage-Thomas Jonelle M
Published: January 2022

Purpose

On our picture archiving and communication system worklist, there was no way to differentiate body imaging (BI) from musculoskeletal (MSK) MR pelvis examinations. They were listed on only the BI worklist. This resulted in ‘lost’ MSK MR pelvis studies with high report turnaround time (TAT). Some exams had preliminary reports with substantiative changes made days later when found. The goals of this project were to create a solution to prevent ‘lost’ exams and improve TAT.

Methods

A report of 3 months of MR pelvis studies was reviewed to determine time to first view by MSK radiologists, time of completion, time of preliminary report and time of final signature. Mean TAT was calculated and exams with delays in reporting resident misinterpretation recorded.

An MSK reserve flag was created for the BI radiologists to use when they found an MSK study on their worklist. The flag moved them onto the MSK reserve worklist. A second intervention included technologists placing the reserve on examination completion. After this, another 3 months of data was analysed.

Results

There was a significant improvement (p=0.0018) in time to view by MSK from preintervention mean of 1125 min (n=107) to postintervention mean of 526 min (n=127). There was also a significant improvement (p=0.0033) in time to view inpatient and Emergency department cases from 927 min to 357 min. Time from study completion to final signature also improved from a mean of 1764 min to 838 min, though not statistically significant (p=0.08). There were five cases of delay in reporting resident misinterpretation preintervention and none postintervention.

Conclusion

Our intervention shows the importance of modifying human and informatics factors to solve a patient safety issue.Introduction
Long-acting reversible contraception and satisfaction with structured contraceptive counselling among non-migrant, foreign-born migrant and second-generation migrant women: evidence from a cluster randomised controlled trial (the LOWE trial) in Sweden
Authors: Emtell Iwarsson Karin , Larsson Elin C , Bizjak Isabella , Envall Niklas , Kopp Kallner Helena , Gemzell-Danielsson Kristina
Published: January 2022

Objective

This trial aimed to evaluate effects of structured contraceptive counselling among non-migrants, foreign-born migrants and second-generation migrants.

Methods

A cluster randomised controlled trial was conducted in 2017–2019 at abortion, youth and maternal health clinics in Stockholm, Sweden (the LOWE trial). Patients were eligible if they were 18 years or older, could understand Swedish or English (or if assisted by an interpreter), were sexually active or planning to be, and were seeking contraception for pregnancy prevention. We randomised clinics at a 1:1 allocation ratio to give either structured contraceptive counselling (intervention) or to maintain standard contraceptive counselling (control). Blinding was not deemed feasibile. A study-specific package for structured contraceptive counselling was used and comprised an educational video, an effectiveness chart, four key questions and a box with contraceptive models. Outcomes were effects of the intervention on long-acting reversible contraception (LARC) choice, initiation and use, and satisfaction with the intervention material among the participants.

Results

We involved 14 clinics in each of the intervention and control groups, respectively. A total of 1295 participants were included: 1010 non-migrants, 169 foreign-born migrants and 116 second-generation migrants. Participants in the intervention group chose LARC to a higher extent than the control group (adjusted OR (aOR) 2.85, 95% CI 2.04–3.99), had higher LARC initiation rates (aOR 2.90, 95% CI 1.97 to 4.27) and higher LARC use within the 12-month follow-up period (aOR 2.09, 95% CI 1.47 to 2.96). The majority of the participants who received the intervention package found all the different parts to be supportive in contraceptive choice. The effectiveness chart was the only part of the package that a higher proportion of foreign-born migrants (58/84, 69%) and second-generation migrants (40/54, 74.1%) found supportive in contraceptive choice compared to non-migrants (259/434, 59.7%) (p = 0.048).

Conclusions

Structured contraceptive counselling increased LARC choice, initiation and use, controlled for participants’ migration background. The effectiveness chart was found to be significantly more supportive among foreign-born migrants and second-generation migrants compared to non-migrants when choosing contraceptive methods.

Trial registration number

NCT03269357.
Excessive daytime sleepiness: an emerging marker of cardiovascular risk
Authors: Bock Joshua , Covassin Naima , Somers Virend
Published: January 2022

Excessive daytime sleepiness (EDS) is classically viewed as a consequence of insufficient sleep or a symptom of sleep disorders. Epidemiological and clinical evidence have shown that patients reporting EDS in tandem with sleep disorders (e.g., obstructive sleep apnoea) are at greater cardiovascular risk than non-sleepy patients. While this may simply be attributable to EDS being present in patients with a more severe condition, treatment of sleep disorders does not consistently alleviate EDS, indicating potential aetiological differences. Moreover, not all patients with sleep disorders report EDS, and daytime sleepiness may be present even in the absence of any identifiable sleep disorder; thus, EDS could represent an independent pathophysiology. The purpose of this review is twofold: first, to highlight evidence that EDS increases cardiovascular risk in the presence of sleep disorders such as obstructive sleep apnoea, narcolepsy and idiopathic hypersomnia and second, to propose the notion that EDS may also increase cardiovascular risk in the absence of known sleep disorders, as supported by some epidemiological and observational data. We further highlight preliminary evidence suggesting systemic inflammation, which could be attributable to dysfunction of the gut microbiome and adipose tissue, as well as deleterious epigenetic changes, may promote EDS while also increasing cardiovascular risk; however, these pathways may be reciprocal and/or circumstantial. Additionally, gaps within the literature are noted followed by directions for future research.
Tumor mutation burden for predicting immune checkpoint blockade response: the more, the better
Authors: Zheng Ming
Published: January 2022

Background

Recently, the US Food and Drug Administration (FDA) has approved immune checkpoint blockade (ICB) for treating cancer patients with tumor mutation burden (TMB) >10 mutations/megabase (mut/Mb). However, high TMB (TMB-H) defined by >10 mut/Mb fails to predict ICB response across different cancer types, which has raised serious concerns on the current FDA approval. Thus, to better implement TMB as a robust biomarker of ICB response, an optimal and generalizable TMB cut-off within and across cancer types must be addressed as soon as possible.

Methods

Using Morris’s and Kurzrock’s cohorts (n=1662 and 102), we exhaustively tested all possible TMB cut-offs for predicting ICB treatment outcomes in 10 cancer types. The bootstrap method was applied to generate 10,000 randomly resampled cohorts using original cohorts to measure the reproducibility of TMB cut-off. ICB treatment outcomes were analyzed by overall survival, progression-free survival and objective response rate.

Results

No universally valid TMB cut-off was available for all cancer types. Only in cancer types with higher TMB (category I), such as melanoma, colorectal cancer, bladder cancer, and non-small cell lung cancer, the associations between TMB-H and ICB treatment outcomes were less affected by TMB cut-off selection. Moreover, high TMB (category I) cancer types shared a wide range of TMB cut-offs and a universally optimal TMB cut-off of 13 mut/Mb for predicting favorable ICB outcomes. In contrast, low TMB (category II) cancer types, for which the prognostic associations were sensitive to TMB cut-off selection, showed markedly limited and distinct ranges of significantly favorable TMB cut-offs. Equivalent results were obtained in the analyses of pooled tumors.

Conclusions

Our finding—the correlation that TMB-H is more robustly associated with favorable ICB treatment outcomes in cancer types with higher TMBs—can be used to predict whether TMB could be a robust predictive biomarker in cancer types for which TMB data are available, but ICB treatment has not been investigated. This theory was tested in cancer of unknown primary successfully. Additionally, the universal TMB cut-off of 13 mut/Mb might reveal a general requirement to trigger the sequential cascade from somatic mutations to an effective antitumor immunity.
Single-cell immune signature for detecting early-stage HCC and early assessing anti-PD-1 immunotherapy efficacy
Authors: Shi Jiawei , Liu Junwei , Tu Xiaoxuan , Li Bin , Tong Zhou , Wang Tian , Zheng Yi , Shi Hongyu , Zeng Xun , Chen Wei , Yin Weiwei , Fang Weijia
Published: January 2022

Background

The early diagnosis of hepatocellular carcinoma (HCC) can greatly improve patients’ 5-year survival rate, and the early efficacy assessment is important for oncologists to harness the anti-programmed cell death protein 1 (PD-1) immunotherapy in patients with advanced HCC. The lack of effective predicting biomarkers not only leads to delayed detection of the disease but also results in ineffective immunotherapy and limited clinical survival benefit.

Methods

We exploited the single-cell approach (cytometry by time of flight (CyTOF)) to analyze peripheral blood mononuclear cells from multicohorts of human samples. Immune signatures for different stages of patients with HCC were systematically profiled and statistically compared. Furthermore, the dynamic changes of peripheral immune compositions for both first-line and second-line patients with HCC after anti-PD-1 monotherapy were also evaluated and systematically compared.

Results

We identified stage-specific immune signatures for HCC and constructed a logistic AdaBoost-SVM classifier based on these signatures. The classifier provided superior performance in predicting early-stage HCC over the commonly used serum alpha-fetoprotein level. We also revealed the treatment stage-specific immune signatures from peripheral blood and their dynamical changing patterns, all of which were integrated to achieve early discrimination of patients with non-durable benefit for both first-line and second-line anti-PD-1 monotherapies.

Conclusions

Our newly identified single-cell peripheral immune signatures provide promising non-invasive biomarkers for early detection of HCC and early assessment for anti-PD-1 immunotherapy efficacy in patients with advanced HCC. These new findings can potentially facilitate early diagnosis and novel immunotherapy for patients with HCC in future practice and further guide the utility of CyTOF in clinical translation of cancer research.

Trial registration numbers

NCT02576509andNCT02989922.