bluuebunny/crossref_metadata_2025 huggingface dataset:
Simulation of a Subcooled Boiling Experiment Using RELAP5/MOD3.2 Computer Code
Authors: Hari Sridhar , Hassan Yassin A. , Tu Jiyuan Y.
Published: January 2022

The results of a low-pressure subcooled flow boiling experiment simulated with the RELAP5/MOD3.2 thermal-hydraulic computer program are presented. The objective of the present study is to assess the suitability of application of the RELAP5 computer program for the thermal hydraulic safety analysis of research reactors. These reactors as the High Flux Australian reactor HIFAR operate at near-atmospheric pressures with upward forced convective flow. Subcooled boiling phenomenon plays an important role in the heat transfer aspects of this reactor. It is found that the void fraction profile predicted by the code for the various experimental conditions differ considerably from the experimental results.
Analysis of VVER1000/320 Operational Transient With CATHARE Computer Program
Authors: Troshko Andrey A. , Hassan Yassin A.
Published: January 2022

A simulation of VVER1000/320 operational transient with CATHARE2 V1.3L was performed. This transient consisted of shutdown of primary side pump in one of the loops. Before the transient, reactor was at nominal operational condition with 72% power level.

The results of comparison between calculated and measured data indicated that the code was able to reasonably reproduce main phenomena taking place in both primary and secondary sides.
High Cycle Fatigue Behavior and Notch Size Effects in Ti-6Al-4V
Authors: Lanning David B. , Haritos George K. , Nicholas Theodore
Published: January 2022

The notch size effect of forged Ti-6Al-4V plate, loaded under high cycle fatigue (HCF) conditions, is investigated for both cylindrical and flat fatigue specimens. Cylindrical specimens were machined with three sizes of circumferential V-notches, with the smallest size dictated by the ability to machine within given tolerances. Flat dogbone specimens were machined with two sizes of opposite V-notches. All notches in both cylindrical and flat specimens have an elastic stress concentration factor of approximately Kt = 2.7. The state of stress at the notch root in the cylindrical specimens is biaxial. Thin flat specimens were chosen with the intent of minimizing the out-of-plane (through the thickness) stress component at the notch root. All specimens were cycled to obtain points on a Haigh diagram, also referred to as the modified Goodman diagram, for a constant life of 106 fatigue cycles. Specimens were cycled at stress ratios of R = 0.1, 0.5, and 0.8, at a frequency of 50 Hz. A step loading technique for generating a point on the Haigh diagram from a single test specimen was used, where the fatigue limit is found by fatiguing the specimen for 106 cycles at a stress level below which failure is expected. If failure does not occur, the stress level is raised and the specimen again fatigued for 106 cycles. This procedure is repeated until failure, after which the fatigue limit is calculated by interpolation. The validity of this technique for Ti-6Al-4V was demonstrated by generating constant amplitude stress-life data for comparison with the interpolated fatigue limits. The notch size effect is examined in light of the stress state at the notch root, and the appropriateness of the von Mises effective stress in characterizing the multiaxial state of stress in HCF is considered.
Effect of Step Testing and Notches on the Endurance Limit of Ti-6Al-4V
Authors: Bellows Richard S. , Bain Ken R. , Sheldon Jerry W.
Published: January 2022

The current Air Force High Cycle Fatigue (HCF) Materials Damage Tolerance Program investigating the fatigue behavior of Ti-6Al-4V requires the determination of initiation-based endurance limits both with and without associated damage modes. Step testing was evaluated as a means of generating endurance limits with a single specimen for the purpose of evaluating associated damage mode states. Notched specimens were evaluated in order to determine the effect of notches on the fatigue behavior so that geometrical effects associated with damage modes could be separated from non-geometrical (e.g., plasticity, residual stresses, cracking) effects. As part of this program, smooth bar S-N curves were generated at four stress ratios (−1, 0.1, 0.5, and 0.8) and compared to endurance limits determined by the step test method using a single specimen. Notch fatigue was conducted at two stress ratios and compared to smooth bar fatigue, and the effect of notch geometry and sampling volume under the notches was examined at a stress ratio of 0.1. The step test method agreed with the conventional S-N curve determined endurance limit in most cases. The different notch geometries and sampling volumes did not appear to effect notch fatigue behavior. This paper presents some of the preliminary results of this ongoing effort.
Mechanistically-Based Fracture Mechanics Models for the Prediction of Multiple Semi-Elliptical Crack Growth in Q1N (HY80) Pressure Vessel Steel Under Fatigue Loading
Authors: Soboyejo W. O. , Knott J. F.
Published: January 2022

Mechanistically-based fracture mechanics models are presented for the prediction of multiple semi-elliptical crack growth in Q1N (HY80) pressure vessel steel. Following a review of the mechanisms of multiple coplanar and non-coplanar semi-elliptical fatigue crack growth, mechanistically-based fracture mechanics models are presented for the prediction of fatigue crack growth. The models include simplified fracture mechanics idealizations of crack interaction and coalescence of coplanar and offset non-coplanar cracks. Predictions obtained from the models are shown to be in closer agreement with measured fatigue crack growth data than the predictions obtained from current ASME Section XI and BS PD 6493 codes. The implications of the models are discussed for the prediction of fatigue life of structures and components that contain multiple configurations of semi-elliptical fatigue cracks.
Structure and Behavior of Materials for Micromechanical Devices
Authors: Krulevitch Peter , Seward Kirk P. , Ackler Harold D. , Johnson George C. , Howe Roger T.
Published: January 2022

The mechanical behavior of thin film microfabricated devices depends in large part on the material microstructure, which in turn depends on the conditions under which the films are deposited. As a result of material sensitivities to various deposition parameters, new techniques have been developed for thorough characterization and monitoring of film properties such as modulus, residual stress, microactuator force generation, and fatigue. Residual stresses in films, which can lead to fracture, buckling, or curling of surface micromachined devices and can influence microactuator behavior, vary considerably with processing conditions. A study of as-deposited in situ phosphorus doped polycrystalline silicon shows a strong correlation between microstructure and residual stress. The gradient in residual stress through the film thickness was determined by measuring the substrate’s curvature, then etching away a thin layer of the film with a plasma etch, and repeating the process until the entire film was removed. These measurements were then compared with cross-sectional transmission electron micrographs of the films, an example of which is shown in Fig. 1. While the overall stress is compressive, crystallization occurring near the substrate results in a tensile stress component, inducing a stress gradient.
MEMS-Based Test Structures for IC Technology
Authors: Smee Stephen A. , Gaitan Michael , Joshi Yogendra
Published: January 2022

As Integrated Circuit (IC) device sizes shrink, intrinsic and thermo-mechanical stress in interconnects is an ever increasing reliability concern. Increasing device density leads to more interconnect layers and hence, greater probability of stress related failure through mechanisms such as electromigration, delamination and voids. Current state-of-the-art IC technology uses 5 interconnect layers. According to the 1997 SIA Roadmap, that number is expected to increase to 9 by the year 2012 [1]. As a result, methods to measure, model and reduce stresses in interconnects are needed to manufacture reliable, future generation IC’s.
Correlation of Fracture Initiation for Microscale Structures: Free-Standing Silicon and Silicon/Glass Interfaces
Authors: Dunn Martin L. , Suwito Wan , Labossiere Paul E. W. , Cunningham Shawn J.
Published: January 2022

We present recent results regarding correlation of fracture initiation for i) micromachined epitaxial silicon structures, and ii) silicon/glass anodic bonds used for encapulation of microelectromechanical systems. Regarding the epitaxial silicon structures, we have previously correlated fracture initiation from the sharp notches that arise during anisotropic etching in KOH using a critical value of the stress intensity that exists in the context of linear elasticity. This has successfully explained an interesting strength scaling with structural dimensions. In this talk, we present new results along these lines where we have considered additional structure geometries (double-edge-notched silicon specimens, roughly 600 μm long × 50 μm wide × 15 μm thick), loadings (in-plane flexure), and etching processes (deep reactive ion etching). Regarding fracture initiation of silicon/glass anodic bonds, we have fabricated a series of generic test structures by anodically bonding etched silicon wafers to glass wafers. We have carried out preliminary tests in tensile and flexural loading and interpreted these results in the framework of an analysis of the singular stress state at the resulting bimaterial notch. For both cases, we will discuss the suitability of using critical stress intensities to correlate fracture initiation under the condition of small-scale inelastic effects.
Load Transfer Characteristics in Metal/Matrix Composites due to a Fiber Breakage
Authors: Folias E. S.
Published: January 2022

In this study, the load transfer characteristics of a broken fiber are investigated. The problem consists of a cylindrical fiber that is embedded into a matrix material. The fiber axis is assumed to coincide with the z-axis and a crack is assumed to be present on the plane z = 0 and for r < a. Far away from the crack, the fiber is subjected to a uniform external load σo.

Moreover, adjacent to the crack and along the interface, the matrix and fiber surfaces are assumed to slide along the interface length −c < z < c, in the presence of a variable frictional force. On the other hand, perfect bonding is assumed to prevail all along the remaining interface, i.e., for |z| > c.

For the solution of the problem, we utilize a Fourier Integral Transform whereby we reduce the problem to that of the solution of a singular integral equation along the interface path −c < z < c. The solution of the integral equation then allows the determination of the displacement and stress fields. Two areas of special interest immediately come to mind, (I) the neighborhood adjacent to the point |z| = c and r = a, and (ii) the neighborhood adjacent to the point z = 0 and r = a.

The analysis reveals that the usual stress singularity which is characteristic to problems of dissimilar materials with friction prevails and that the interface shear stress is non-uniform. Moreover, the ratio of fiber jump over fiber diameter is found to be related to the applied load as well as the material properties.
Prediction of Damage Evolution in Laminated Composites Subjected to Impact Loading
Authors: Allen D. H. , Searcy C. R.
Published: January 2022

Many structural components undergo significant structural damage when they are subjected to ballistic impact. Because this damage can lead to failure of monolithic components to perform their intended missions, composite structures have recently been developed to better withstand impact. The intent of these new types of composites is to provide tougher, yet lighter structures that will withstand significantly larger ballistic impact energies than do traditional monolithic structures. Although these new composite structures do indeed appear to provide increased toughness, they also undergo much more complicated damage mechanisms, so that it has become difficult to accurately predict the limits of usefulness of structures made with these materials.

It is evident that in order to develop design tools that can be used to assess the performance characteristics of these composite components, it is necessary to develop models that can accurately predict the evolution of damage of various types during actual impact events. This paper outlines a methodology based in continuum mechanics and utilizing advanced damage, fracture, and computational mechanics to obtain accurate predictions of damage evolution in laminated composite structures during ballistic impact. The evolution of damage is accounted for by the use of a cohesive zone model capable of predicting matrix, fiber, and interply cracking in ductile polymers. This model has been implemented to a global three dimensional finite element computer code for the purpose of predicting the evolution of damage during impact. The resulting algorithm is utilized herein to predict the types of damage events experimentally observed in laminated composite plates subjected to impact, and comparisons are made to two experimental results obtained by the author and coworkers.
Crack Propagating in a Bimaterial Functionally Graded Multilayered Composite Media
Authors: Muju Sandeep
Published: January 2022

The macroscopically anisotropic homogenization of a multilayered composite implicitly assumes that the spatial wavelength of material inhomogeneity is smaller than the macroscopic quantity of interest and hence, is a reasonable approximation of the bulk behavior [1]. However, close to the crack tip, gradients in field quantities are strongly influenced by the local heterogeneity, which the anisotropic homogenization fails to capture. Thus, given the insights from a homogenized continuum study, the next level of refinement is to study the effect of inhomogeneity on crack driving force.

Asymptotic studies of cracks perpendicular and parallel to a bimaterial interface and in a layer between two materials have been very widely researched over the past two decades. Recently the advent of the use of functionally gradient materials (FGM) in composites, nano-composites and other multi-material structural systems has spurred interest in the fracture mechanics of such inhomogeneous materials. The problems considered in the literature typically assume a functional form for the material property variation, usually in one direction only, and calculate the driving force at the crack tip for a crack at some orientation to the direction of variation. The interest in FGM’s is due to their superior performance as interfacial layers in general and in particular in high temperature applications. Discontinuities in material properties between joined material constituents act as stress concentrators, especially due to thermal expansion mismatches under thermal processing or service loads. The use of a FGM as an interfacial layer smooths the discontinuity and reduces the stress concentrations.

In this paper an analytic solution for the effect of periodic inhomogeneity on crack driving force is studied. Via Williams eigenfunction expansion approach it is seen that, for continuously differentiable moduli inhomogeneity the nature of the stress singularity at the crack tip is the same as in a homogeneous media, though the eigenvalue (Stress Intensity Factor) does depend on the inhomogeneity [1]. In order to study the effect of layered inhomogeneity on the Stress Intensity Factor(s), the Bueckner-Rice weight function approach for homogeneous media [2–3] is incorporated here to study the layered media problem. In this chapter the moduli perturbation approach, [4], is further extended to the case of multilayered media, especially in a functionally gradient material sense. It is shown that to the first order, the effect of moduli inhomogeneity, residual stresses and inelastic strains on crack tip stress intensity factor are superposable.

The results provide insight into the influence of residual stress and periodic moduli inhomogeneity on effective crack driving force for cracks propagating through multilayered bimaterial media. Further, this method in general allows one to study thermoelastic crack problems in complex heterogeneous media, alleviating difficulties associated with some of the traditional methods.
A Composite-Sheathed Compression Test for Characterizing Pressure-Hardening Materials
Authors: Chou Pei Chi , Flis William J.
Published: January 2022

Knowledge of the constitutive behavior of explosives is necessary for the development of exploding devices that are safe to handle and transport and that are effective in use. The plastic deformation of most explosives is strongly affected by pressure and by strain rate. Pressure-hardening effects may be determined directly by a uniaxial-compression test performed in a special hydraulic apparatus that applies a lateral pressure to the specimen. However, the apparatus is expensive and testing explosives presents some risk to it.

Previously, to investigate both pressure- and rate-hardening effects, we developed a modified Taylor cylinder-impact test in which the explosive specimen is encased in a confining sheath (or sleeve) of a well-characterized material, typically a ductile metal such as copper. The sheath, which is stiffer than the explosive, serves to confine the specimen to provide increased pressure and also maintains its integrity. Computations using a large-deformation dynamic plasticity code (hydrocode) are then fitted to the test results (the shape of the deformed specimen) to provide an estimate of the constitutive parameters.

To refine our results, we are currently developing a similar quasi-static compression test that uses a confining sheath to develop the pressure in the specimen. In our cylinder-impact tests, the copper sheath was able to generate pressures up to about 0.5 GPa. In quasi-static compression tests, however, a copper sheath fails at much lower pressures. To provide the higher pressures required, we are using instead a sheath of graphite- or glass-fiber composite material. The fibers are aligned in the circumferential direction to provide a very large hoop strength, with little axial stiffness. The axial load is thus carried mainly by the explosive specimen.

To design the sleeve and for post-test fitting of results, we have modified a finite-element hydrocode to include an anisotropic (orthotropic) elastic-plastic constitutive formulation to model the composite. Compressibility behavior is modeled using an established fit to Murnaghan_s pressure-volume relation. To describe the yield surface, both the simple Drucker-Prager criterion and a non-linear relation will be tried.

This test will be used to characterize first mock explosives, then, once validated, actual explosives. Advantages of the new test include economy and low risk of damage to test equipment.
An Overview of Shear Deformation Theories and Their Relationships to the Classical Theory
Authors: Reddy J. N.
Published: January 2022

The paper presents a review of various shear deformation theories of beams and plates and a critical evaluation of the theories from analysis points of view. In particular post-computation of stresses in composites is revisited and alternative approaches are discussed in light of Pagano’s works on the subject. In addition, relationships for bending, vibration, and buckling solutions of shear deformation theories in terms of the corresponding solutions of the classical theory are discussed. These relationships may be used to determine the solutions of shear deformation theories by knowing the corresponding solutions of the classical theory. These relationships are also used to develop finite element models of the shear deformation theories of beams and plates. These finite element models, unlike the conventional finite element models, are free of so-called shear locking.

Dedication: This work is dedicated to Nicholas J. Pagano, a friend and colleague, on his sixty fifth birthday.
Damage Initiation and Progression in Multidirectional Laminates With a Hole
Authors: Schaff J. R. , Kim R. Y.
Published: January 2022

Holes are pervasive in load-bearing composite structures within the aerospace industry, as a result of the use of mechanical fasteners in assembly and cutouts to accommodate wiring and hydraulic lines. In this work, static loading experiments were conducted on composite laminates to document the initiation and growth of damage and to record changes in the strain field. The main objective of this work was the development of an experimental database for comparison with the results from a three-dimensional stress analysis based on spline variational theory. Two multidirectional laminates considered in this study were [0/90]2s and [±30/90]s of IM7/5250-4 (graphite fiber/toughened BMI). For each loading increment strains were recorded at a number of locations in close proximity to the hole as well as far field, and the specimen was subjected to x-radiography. Acoustic emission was also monitored during loading and compared to strains and radiographic images to identify damage initiation and progression. Experimental strains were well with the analytical strains at low loadings, prior to extensive damage development. The details of damage progression in these laminates discussed.
Composite Technology Insights That Will Enable the Next Generation Space Telescope
Authors: Kedward Keith T.
Published: January 2022

Opportunities for polymer matrix composites (PMC’s) in lightweight spacecraft structures and systems are already extensive and will further expand as sophisticated space communications systems applications are introduced. One specific area where the unique properties provided by carbon and graphite fiber-reinforced polymeric matrix composites are particularly attractive is in the next generation, ultra-lightweight, high precision optical instruments. In this paper the Next Generation Space Telescope (NGST) application will be used to illustrate the enabling features of PMC’s.

Areal density is one parameter used to indicate weight trends for primary mirror structures. The State-of-the-Art (SOA) value for difraction-limited visible systems is 25–30 kg/m2. Technology developments will be described to demonstrate that areal density of less than 50% of the SOA, i.e., 10–15 kg/m2, are now feasible. One design approach that combines the most recently developed fiber and matrix systems in the form of a hybrid sandwich structure supporting an isogrid-stiffened Zerodur surface is illustrated in Figure 1.

Constituents for the core structure comprise ultra-high modulus graphite fiber and cyanate ester resin matrix selected for its combination of high specific stiffness, near-zero thermal expansion properties, as well as manufacturing flexibility. Designated specific systems are M55J/954-3 and K1352U/954-3. This high specific stiffness has resulted in a preliminary design concept that provides a fundamental resonance frequency (predicted) of an acceptable 150 Hz depending on the precise arrangement of flexures as well as the projected weight saving goal.

The paper will emphasize the importance of thorough technical insights in the engineering of such complex, high precision structures that are based on highly anisotropic heterogeneous systems. This precision demands very careful consideration of cyclical environmental/ temperature dependent distortional behavior and “timing” of the coefficient of thermal expansion. It will be explained that stress vs. strain, and load vs. displacement, relationships of the specific adhesive system used for bonding the Zerodur facesheet to the composite core structure, must be properly characterized over the temperature range from processing conditions to operational limits.

The effects of the reflective coating applied to the mirror surface is also addressed in assessing its influence on optical performance by use of interferometric measurements at ambient and cryogenic temperatures before and after application of the coating.
Fracture Behavior of Kaolin-Reinforced High Density Polyethylene
Authors: Wetherhold Robert C. , Mouzakis Dionysios E.
Published: January 2022

The addition of the low-cost mineral filler kaolin to high-density polyethylene (HDPE) creates a composite with both improved stiffness and toughness properties. This study focuses on two aspects of the toughness of these composites: the fracture toughness increment produced by work at the fracture surface and the directionality induced by the injection molding fabrication process. The Essential Work of Fracture (EWF) method gives results which show that a higher volume fraction of kaolin produces more surface work, consistent with earlier work using Compact Tension (CT) tests. The EWF method also demonstrates that a lower volume fraction can produce a higher overall plastic work and apparent toughness. A heat treatment which removes the orientation of the matrix but not that of the particles was applied to study the effect of matrix crystallinity. The results indicate that the matrix supramolecular structure (crystallinity and skin-core effect) is responsible for the directionality of toughness, and that a heat treatment can be used to produce high toughness behavior in both major directions.
Experiments with mobile devices — A retrospective on 10 years of iPhysicsLabs
Authors: Kuhn Jochen , Vogt Patrik
Published: January 2022

The TPT column “iPhysicsLabs,” which describes an experiment using mobile devices in each article, has been around for exactly 10 years now. We would like to take this anniversary as an opportunity to take stock and to thank the colleagues without whom the column would not be possible in this form.
The Sleep Behaviors of Elite Australian Rules Footballers Before and After Games During an Entire Season
Authors: Sargent Charli , Rogalski Brent , Montero Ashley , Roach Gregory D.
Published: January 2022

Purpose: Most athletes sleep poorly around competition. The aim of this study was to examine sleep before/after games during an entire season in elite Australian Rules footballers (N = 37) from the same team. Methods: Sleep was monitored using activity monitors for 4 consecutive nights (beginning 2 nights before games) during 19 rounds of a season. Differences in sleep on the nights before/after games, and differences in sleep before/after games as a function of game time (day vs evening), location (local vs interstate), and outcome (win vs loss), were examined using linear mixed effects models. Results: Players fell asleep earlier (+1.9 h; P < .001), and woke up later (+1 h; P < .001) on the night before games compared with the night of games. Players obtained less sleep on the night of games than on the night before games (5.2 h vs 7.7 h; P < .001), and this reduction was exacerbated when games were played in the evening—after evening games, players obtained approximately 40 minutes less sleep than after day games (P < .001). Sleep duration on the nights before and after games was not affected by game location or game outcome, but players had later sleep onset (P < .001) and offset times (P < .001) on most nights when sleeping away from home. Conclusions: Elite footballers obtain good sleep on the night before games but obtain approximately 30% less sleep on the night of games. Given the role of sleep in recovery, it will be important to determine whether a reduction in sleep duration of this magnitude impairs recovery on the days following games.
Model-Based Meta-Analysis of Relapsing Mouse Model Studies from the Critical Path to Tuberculosis Drug Regimens Initiative Database
Authors: Berg Alexander , Clary James , Hanna Debra , Nuermberger Eric , Lenaerts Anne , Ammerman Nicole , Ramey Michelle , Hartley Dan , Hermann David
Published: January 2022

Tuberculosis (TB), the disease caused by
Mycobacterium tuberculosis
 
(Mtb), remains a leading infectious disease-related cause of death worldwide, necessitating the development of new and improved treatment regimens. Nonclinical evaluation of candidate drug combinations via the relapsing mouse model (RMM) is an important step in regimen development, through which candidate regimens that provide the greatest decrease in the probability of relapse following treatment in mice may be identified for further development.
Microscopic Analysis of the Chlamydia abortus Inclusion and Its Interaction with Those Formed by Other Chlamydial Species
Authors: Garvin Lotisha E. , DeBoer Addison G. , Carrell Steven J. , Wang Xisheng , Rockey Daniel D.
Published: January 2022

The Chlamydiae are obligate intracellular pathogens that develop and multiply within a poorly characterized parasitophorous vacuole (the inclusion) during growth.
Chlamydia abortus
is a major pathogen of sheep and other ruminants, and its inclusion development is poorly characterized. We used immunofluorescence microscopy, quantitative culture, and qPCR to examine
C. abortus
inclusion development and to examine the interaction of
C. abortus
inclusions with those formed by other species.
Use of Digital Whiteboard to Engage Undergraduates in Online Studies of Instructor-Generated Biological Diagrams
Authors: Mendez Aura , Brioso Juleissy , Jaramillo Angie , Premawardena Dhananjaya , Cunningham Emily , Sarran-Armogan Lisa , Zhou Chun
Published: January 2022

The development of critical thinking skills is one of the core values of higher education. As an important aspect of visual literacy in the core competencies of undergraduate biology teaching, diagram learning activities have been shown to facilitate students’ gains in understanding biology concepts and improving critical thinking skills.
Treatment strategies and long-term outcomes in patients with congenital microphthalmia–anophthalmia with cyst
Authors: Gore Sri , Grimaldi Gabriela , Mazzone Giacomilde , Collin Richard , Savino Gustavo , Pagnoni Mario , Modugno Alessandra
Published: January 2022

Background/Aims

Microphthalmia and anophthalmia are rare conditions, which represent ocular maldevelopment; both may be associated with orbital cysts. Current literature recommends retention to stimulate orbital growth during socket rehabilitation but does not illustrate their potential to deform the periocular tissues. This study aims to illustrate the long-term outcomes when other elements, such as forniceal and lid development, are also considered when formulating bespoke treatment plans for patients.

Methods

Retrospective case series of 78 patients attending a single prosthetics clinic between 1988 and 2020. Clinical and surgical notes, radiological imaging, clinical photographs and patient/doctor satisfaction questionnaires were used to report patient outcomes and natural history data.

Results

89 sockets of 78 patients (11 bilateral) were included; average age of presentation being 2.8 years (9 days to 29.5 years). Cysts were clinically detected (48%) or were incidental findings (52%). The mean follow-up time was 7.2 years (6 months to 28 years). Cysts in 46% of sockets underwent surgical excision while the remainder were retained. Satisfaction surveys were obtained for 75 patients, with cosmetic outcomes rated as ‘excellent’ or ‘good’ in 90% of cases by physicians and 97% of cases by patients or guardians.

Conclusion

The favourable long-term outcomes in this study have resulted from bespoke plans which considered periocular tissue development, regional orbital growth and orbital volume replacement. The authors contemplate cyst excision if the prosthetic fitting or retention is impeded by the cyst as this often heralds the increased risk of long-term periocular distortion.
Real-world weight change, adherence, and discontinuation among patients with type 2 diabetes initiating glucagon-like peptide-1 receptor agonists in the UK
Authors: Weiss Tracey , Yang Lingfeng , Carr Richard D , Pal Sampriti , Sawhney Baanie , Boggs Robert , Rajpathak Swapnil , Iglay Kristy
Published: January 2022

Introduction

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a type 2 diabetes mellitus (T2DM) treatment with demonstrated weight loss benefits in clinical trials. However, the extent to which real-world patients with T2DM achieve clinically meaningful weight loss (≥5%) has not been well characterized. Analysis of real-world data suggests adherence to injectable GLP-1 RAs is suboptimal and discontinuation following the first year of therapy is poorly characterized.

Research design and methods

A retrospective cohort study among patients with T2DM initiating injectable GLP-1 RA therapy was conducted using the Clinical Practice Research Datalink that includes primary care medical records for 13 million patients in the UK. This study assessed weight change, adherence (proportion of days covered (PDC) ≥80%), and discontinuation (≥90-day gap between prescriptions) at 12 and 24 months during the study period spanning January 2009–December 2017.

Results

Among 589 patients initiating a GLP-1 RA, 56.4% were female and the median age was 54 years (IQR (46, 61)). The median body mass index was 41.2 kg/m2(IQR (35.8, 46.4)). Among patients with weight measures available (n=341 at 12 months; n=232 at 24 months), 33.4% and 43.5% achieved weight loss ≥5% of baseline weight at 12 and 24 months, respectively. At 12 and 24 months, 64.5% and 59.2% were adherent, and 45.2% and 64.7% discontinued, respectively.

Conclusions

A minority of patients initiating GLP-1 RAs achieved ≥5% weight loss, suggesting the real-world benefit of these agents on weight loss may be lower than that observed in clinical trials. Patients on GLP-1 RAs may benefit from additional support to improve long-term adherence.
Impact of community education on heat-related health outcomes and heat literacy among low-income communities in Karachi, Pakistan: a randomised controlled trial
Authors: Razzak Junaid Abdul , Agrawal Priyanka , Chand Zaheer , Quraishy Saadia , Ghaffar Abdul , Hyder Adnan A
Published: January 2022

Background

Extreme heat exposure is a growing public health concern. In this trial, we tested the impact of a community health worker (CHW) led heat education programme on all-cause mortality, unplanned hospital visits and changes in knowledge and practices in Karachi, Pakistan.

Methods

The Heat Emergency Awareness and Treatment trial was a community-based, open-label, two-group, unblinded cluster-randomised controlled trial that implemented a CHW-led educational intervention between March and May 2018 in Karachi, Pakistan. We randomly assigned (1:1) 16 clusters, each with ~185 households or 1000 population, to the intervention or usual care (control group). We collected data on all-cause mortality, unplanned hospital visits, evidence of heat illness through surveillance and a knowledge and practice survey during the summer months of 2017 (preintervention) and 2018 (postintervention).

Findings

We recruited 18 554 participants from 2991 households (9877 individuals (1593 households) in the control group and 8668 individuals (1398 households) in the intervention group). After controlling for temporal trends, there was a 38% (adjusted OR 0.62, 95% CI 0.49 to 0.77) reduction in hospital visits for any cause in the intervention group compared with the control group. In addition, there was an improvement in many areas of knowledge and practices, but there was no significant difference in all-cause mortality.

Interpretation

A CHW-led community intervention was associated with decreased unscheduled hospital visits, improved heat literacy and practices but did not impact all-cause mortality. CHWs could play an essential role in preparing communities for extreme heat events.

Trial registration number

NCT03513315.
A qualitative analysis of medical students’ attitudes to abortion education in UK medical schools
Authors: Horan Corrina , Zadeh Persia Ghassem , Rennison Catriona , Hoggart Lesley , Kavanagh Jayne
Published: January 2022

Background

Despite abortion being a common part of reproductive healthcare, UK undergraduate medical school abortion education varies widely. We therefore aimed to explore medical students’ views on their undergraduate abortion education, including whether it prepared them to be a competent practitioner.

Methods

We conducted in-depth semi-structured interviews with 19 students from five UK medical schools, all of whom had received abortion teaching. The qualitative research followed a quantitative survey of UK undergraduate abortion education; the five medical schools were purposively sampled to encompass a wide variety of teaching approaches. Interviews were transcribed and data were analysed using an inductive thematic approach.

Results

Dedicated abortion teaching was highlighted as necessary and valuable, as abortion care is so commonly accessed. Participants felt that abortion education should prepare students to be competent practitioners, with inclusion of clinical placements and an emphasis on non-stigmatising care. Most interviewees felt that the perceived sensitive nature of abortion should act as an incentive to comprehensive teaching. It was suggested that teaching should be inclusive for all, including those with a conscientious objection to abortion.

Conclusion

The medical students interviewed viewed comprehensive abortion education as an important aspect of their undergraduate curriculum. Conversely to the accompanying quantitative survey of educators, participants believed that the perceived sensitivity of abortion increases the importance of effective teaching that prepares them to provide competent respectful care when they qualify. It is incumbent on medical schools to provide the comprehensive education that students need and the Royal College of Obstetricians and Gynaecologists recommends.
Tumor mutational burden predicts the efficacy of pembrolizumab monotherapy: a pan-tumor retrospective analysis of participants with advanced solid tumors
Authors: Cristescu Razvan , Aurora-Garg Deepti , Albright Andrew , Xu Lei , Liu Xiao Qiao , Loboda Andrey , Lang Lixin , Jin Fan , Rubin Eric H , Snyder Alexandra , Lunceford Jared
Published: January 2022

Background

Several studies have evaluated the relationship between tumor mutational burden (TMB) and outcomes of immune checkpoint inhibitors. In the phase II KEYNOTE-158 study of pembrolizumab monotherapy for previously treated recurrent or metastatic cancer, high TMB as assessed by the FoundationOne CDx was associated with an improved objective response rate (ORR).

Methods

We retrospectively assessed the relationship between TMB and efficacy in participants with previously treated advanced solid tumors enrolled in 12 trials that evaluated pembrolizumab monotherapy, including 3 randomized trials that compared pembrolizumab with chemotherapy. TMB was assessed in formalin-fixed, paraffin-embedded pretreatment tumor samples by whole-exome sequencing. High TMB was defined as ≥175 mutations/exome. Microsatellite instability (MSI) phenotype was based on whole-exome sequencing results. Programmed death ligand 1 (PD-L1) expression was assessed by immunohistochemistry. The primary end point was ORR assessed per RECIST V.1.1 by independent central review. Other end points included progression-free survival (PFS) assessed per RECIST V.1.1 by independent central review and overall survival (OS).

Results

Of the 2234 participants in the analysis, 1772 received pembrolizumab monotherapy and 462 received chemotherapy. Among the pembrolizumab-treated participants, ORR was 31.4% (95% CI 27.1 to 36.0) in the 433 participants with TMB ≥175 mutations/exome and 9.5% (95% CI 8.0 to 11.2) in the 1339 participants with TMB <175 mutations/exome. The association of TMB with ORR was observed regardless of PD-L1 expression and not driven by specific tumor types or participants with very high TMB or high MSI. In the 3 randomized controlled trials, TMB was associated with ORR (p≤0.016), PFS (p≤0.005), and OS (p≤0.029) of pembrolizumab but not of chemotherapy (p≥0.340, p≥0.643, and p≥0.174, respectively), and pembrolizumab improved efficacy versus chemotherapy in participants with TMB ≥175 mutations/exome.

Conclusions

TMB ≥175 mutations/exome is associated with clinically meaningful improvement in the efficacy of pembrolizumab monotherapy and improved outcomes for pembrolizumab versus chemotherapy across a wide range of previously treated advanced solid tumor types. These data suggest TMB has broad clinical utility irrespective of tumor type, PD-L1 expression, or MSI status and support its use as a predictive biomarker for pembrolizumab monotherapy in participants with previously treated advanced solid tumors.
Drivers and outcomes of variation in surgical versus transcatheter aortic valve replacement in Ontario, Canada: a population-based study
Authors: Miranda Rafael N , Qiu Feng , Manoragavan Ragavie , Fremes Stephen , Lauck Sandra , Sun Louise , Tarola Christopher , Tam Derrick Y , Mamas Mamas , Wijeysundera Harindra C
Published: January 2022

Objectives

To understand the patient and hospital level drivers of the variation in surgical versus trascatheter aortic valve replacement (SAVR vs TAVR) for patients with aortic stenosis (AS) and to explore whether this variation translates into differences in clinical outcomes.

Background

Adoption of TAVR has grown exponentially worldwide. Notwithstanding, a wide variation in TAVR rates has been seen within and between countries and in some jurisdictions AS is still primarily being managed by SAVR.

Methods

We conducted a population-based retrospective cohort study in Ontario, Canada, including individuals who received TAVR or SAVR between 2016 and 2020. We developed iterative hierarchical logistic regression models for the likelihood of receiving TAVR instead of SAVR examining sequentially patient characteristics, hospital factors and year of procedure, calculating the median ORs and variance partition coefficients for each. Using Cox proportional hazards models, we examined the relationship between TAVR/SAVR ratio on all-cause mortality and readmissions.

Results

Annual procedures rates per million population increased from 171 to 201, mainly driven by the expansion of TAVR. TAVR/SAVR ratios differed substantially between hospitals, from 0.21 to 3.27. Neither patient nor hospital factors explained the between-hospital variation in AS treatment. The TAVR/SAVR ratio was significantly associated with clinical outcomes with high ratio hospitals having lower mortality and rehospitalisations.

Conclusions

Despite the expansion of TAVR, dramatic variation exists that is not explained by patient or hospital factors. This variation was associated with differences in clinical outcomes, suggesting that further work is needed in understanding and addressing inequity of access.
Synthesis and photophysical properties of quinoxaline-based blue aggregation-induced emission molecules
Authors: Mao Xiaoyu , Liu Yiwei , Zeng Jin , Wang Xiaohui , Islam Md Monarul , Chen Ming , Chen Qing , Feng Xing
Published: January 2022

A series of quinoxaline-based compounds 1–4 have been synthesized by a palladium-catalyzed cross-coupling reaction and their photophysical properties have been extensively studied. Compounds 1–4 show deep blue light emission both in solution (λem ≤ 425 nm, Commission Internationale de L’Eclairage y (CIEy) ≤ 0.03) and in the solid state. Moreover, compounds 1–3 show a non-typical aggregation-induced enhanced emission (AIEE), which would be effective deep blue light-emitting materials. The DFT calculation indicated that the HOMO energy levels of compounds 1–3 are distributed throughout the molecule, and the LUMO energy levels are mainly concentrated on the quinoxaline group. However, the HOMO of compound 4 is mainly on the benzene ring at 2,3 position, and the LUMO is distributed both of the quinoxaline and the benzaldehyde group at the 6,7 position.
Evaluation of harvest control rules for a group of interacting commercial stocks using a multispecies MSE framework
Authors: Pérez-Rodríguez Alfonso , Umar Ibrahim , Goto Daisuke , Howell Daniel , Mosqueira Iago , González-Troncoso Diana
Published: January 2022

In this study, a multispecies gadget model (GadCap) simulating the interactions among the Flemish Cap cod (Gadus morhua), redfish (Sebastes spp.), and shrimp (Pandalus borealis) has been incorporated as the operating model in a management strategy evaluation (MSE) framework (a4a-FLR) to test the performance of multiple combinations of harvest control rules (HCRs) for the three stocks when recruitment uncertainty and assessment error are accounted for. The results indicate that due to the strong trophic interactions, it is not possible to achieve the precautionary exploitation of all the stocks at the same time. Maintaining shrimp biomass above the limit reference point (Blim) would require unsustainable fishing pressure on cod and redfish to reduce predation mortality. In contrast, maintaining cod biomass above Blim would involve high predation on and high risk of collapse of the shrimp and redfish stocks. The implementation of alternative two-stage HCRs would reduce predation, resulting in higher productivity and lower probability of collapse for cod and redfish. The results of this study support the need of accounting for species interactions when designing management strategies for a group of interdependent commercial stocks.
Environmental drivers of herring growth and how the perception shifts with time series length
Authors: Claireaux Marion , Zimmermann Fabian , Ernande Bruno , Heino Mikko , Enberg Katja
Published: January 2022

Growth is a key component of population dynamics and, thus, fisheries management, yet drivers of its variations are often poorly understood. Using individual data collected over 80 years, we explored how environmental drivers affect growth in a major population of Atlantic herring (Clupea harengus). The results confirm that intrinsic factors (age and maturation) determine growth to a large degree but also that extrinsic factors such as temperature have some influence. While the role of intrinsic factors was independent of time series length, the importance of extrinsic drivers varies strongly with the analysed time period. It remains unclear whether this is caused by data inconsistencies back in time, spurious correlations appearing in shorter time series, shifts in population dynamics, or dynamic interactions between variables that cannot be determined with current data. Generally, environmental effects on growth became less clear and relevant with increasing time series length. What drives variation in growth may therefore change over time, potentially due to impacts such as fishing or climate change. It also underlines that seemingly clear correlations can break down or change their sign over time; hence, caution is advised when interpreting results from time series of 20–40 years.