bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of a Convolutional Neural Network for Wave Mode Identification in a Rotating Detonation Combustor Using High-Speed Imaging
Authors: Johnson Kristyn B. , Ferguson Donald H. , Tempke Robert S. , Nix Andrew C.
Published: January 2021

Utilizing a neural network, individual down-axis images of combustion waves in the rotating detonation engine (RDE) can be classified according to the number of detonation waves present and their directional behavior. While the ability to identify the number of waves present within individual images might be intuitive, the further classification of wave rotational direction is a result of the detonation wave’s profile, which suggests its angular direction of movement. The application of deep learning is highly adaptive and, therefore, can be trained for a variety of image collection methods across RDE study platforms. In this study, a supervised approach is employed where a series of manually classified images is provided to a neural network for the purpose of optimizing the classification performance of the network. These images, referred to as the training set, are individually labeled as one of ten modes present in an experimental RDE. Possible classifications include deflagration, clockwise and counterclockwise variants of co-rotational detonation waves with quantities ranging from one to three waves, as well as single, double, and triple counter-rotating detonation waves. After training the network, a second set of manually classified images, referred to as the validation set, is used to evaluate the performance of the model. The ability to predict the detonation wave mode in a single image using a trained neural network substantially reduces computational complexity by circumnavigating the need to evaluate the temporal behavior of individual pixel regions throughout time. Results suggest that while image quality is critical, it is possible to accurately identify the modal behavior of detonation waves based on only a single image rather than a sequence of images or signal processing. Successful identification of wave behavior using image classification serves as a steppingstone for further machine learning integration in RDE research and development of comprehensive real-time diagnostics.
Geometric Constraint-Based Reconfiguration and Self-Motions of a Four-CRU Parallel Mechanism
Authors: Nurahmi Latifah , Putrayudanto Pradiktio , Wei Guowu , Agrawal Sunil K.
Published: January 2021

Over the past few years, the concept of multi-directional three-dimensional (3D) printing has been introduced to print complex shapes and overhang geometry. This technique requires the nozzle to constantly change orientation to print the object along its tangential direction. A six-degrees-of-freedom (6-DOF) robotic arm or Stewart platform can be a solution, but these mechanisms use more components and motors. An alternative solution has been proposed in this paper based on a four-CRU (cylindrical, revolute, and universal joints) mechanism. This mechanism can orient the nozzle by switching into different motion types with minimal numbers of motors while keeping the mechanism rigid and agile. Therefore, analyses of the reconfiguration, workspace, singularities, and self-motions of a four-CRU mechanism presented in this paper have become necessities. By using primary decomposition, four geometric constraints have been identified, and the reconfiguration analysis has been carried out in each of these. It reveals that each geometric constraint will have three distinct operation modes, namely Schönflies mode, reversed Schönflies mode, and an additional mode. The additional mode can either be a four-DOF mode or a degenerated three-DOF mode, depending on the type of geometric constraints. By taking into account the actuation and constraint singularities, the workspace of each operation mode has been analyzed and geometrically illustrated. It allows us to determine the regions in which the reconfiguration takes place. Furthermore, the inherent self-motion in the Schönflies mode is revealed and illustrated, which occurs at two specified actuated leg lengths. Demonstration of the reconfiguration process and self-motions is provided through a mock-up prototype.
Development of microfabricated planar slow-wave structures on dielectric substrates for miniaturized millimeter-band traveling-wave tubes
Authors: Ryskin Nikita M. , Torgashov Roman A. , Starodubov Andrey V. , Rozhnev Andrey G. , Serdobintsev Alexey A. , Pavlov Anton M. , Galushka Viktor V. , Bessonov Dmitry A. , Ulisse Giacomo , Krozer Viktor
Published: January 2021

We report the results of the design, simulation, fabrication, and cold-test measurements of millimeter-band 2D planar microstrip slow-wave structures (SWSs) on dielectric substrates. Such structures have a high slow-wave factor, which allows for low-voltage operation and reduction in the size and weight of the device. A low-cost and flexible fabrication technology based on magnetron sputtering and subsequent laser ablation has been developed and is reported in the paper. Microstrip meander-line SWS circuits at V-, W-, and D-bands have been fabricated and characterized. The fabrication of ring-bar planar SWSs by the photolithographic method is also discussed. Experimental measurement of S-parameters of the fabricated structures reveals good transmission properties. Return loss (S11) does not exceed −10 dB and attenuation is about 2 dB/cm in the V-band, 10 dB/cm in the W-band, and 8.5 dB/cm in the D-band.
Bacillus subtilis extracellular polymeric substances conditioning layers inhibit Escherichia coli adhesion to silicon surfaces: A potential candidate for interfacial antifouling additives
Authors: Wu Songze , Hou Wenjia , Suo Xinkun , Guo Xueping , Li Hua
Published: January 2021

Biofouling on material surfaces is a ubiquitous problem in a variety of fields. In aqueous environments, the process of biofouling initiates with the formation of a layer of macromolecules called the conditioning layer on the solid-liquid interface, followed by the adhesion and colonization of planktonic bacteria and the subsequent biofilm development and maturation. In this study, the extracellular polymeric substances (EPS) secreted by Bacillus subtilis were collected and used to prepare conditioning layers on inert surfaces. The morphologies and antifouling performances of the EPS conditioning layers were investigated. It was found that the initial adhesion of Escherichia coli was inhibited on the surfaces precoated with EPS conditioning layers. To further explore the underlying antifouling mechanisms of the EPS conditioning layers, the respective roles of two constituents of B. subtilis EPS (γ-polyglutamic acid and surfactin) were investigated. This study has provided the possibility of developing a novel interfacial antifouling additive with the advantages of easy preparation, nontoxicity, and environmental friendliness.
A rigorous approach to optimal profile design for acoustic black holes
Authors: Støttrup Benjamin B. , Sorokin Sergey , Cornean Horia D.
Published: January 2021

Calculus of variations is used to determine a profile shape for an acoustic black hole without a layer of viscoelastic dampening material with fixed parameters of geometry (i.e., length, maximal and minimal thickness), which minimizes the reflection coefficient, without violating the underlying assumptions of existence for acoustic black holes. The additional constraint imposed by keeping the normalized wave number variation (NWV) small everywhere in the acoustic black hole is handled by the use of Lagrange multipliers. From this method, closed-form expressions for the optimal profile, its reflection coefficient, and the NWV are derived. Additionally, it is shown that in the special case where only the NWV (and not the reflection coefficient) is considered, the optimal profile reduces to the well-known thickness profile for acoustic black holes, h(x)=ϵx2. We give a numerical example of the difference between an acoustic black hole with optimal profile and classical profile, h(x)=ϵxm, m > 2. For close to identical reflection coefficients, the optimal profile vastly outperforms the classical profile in terms of having low NWV at a large range of frequencies.
Molecular design of stapled pentapeptides as building blocks of self-assembled coiled coil–like fibers
Authors: Jiang Yixiang , Zhang Wan , Yang Fadeng , Wan Chuan , Cai Xiang , Liu Jianbo , Zhang Qianling , Li Zigang , Han Wei
Published: January 2021

A joint computational and experimental effort unravels a peptide scaffold for self-assembled nanomaterials.
Hydroclimate footprint of pan-Asian monsoon water isotope during the last deglaciation
Authors: He C. , Liu Z. , Otto-Bliesner B. L. , Brady E.C. , Zhu C. , Tomas R. , Clark P.U. , Zhu J. , Jahn A. , Gu S. , Zhang J. , Nusbaumer J. , Noone D. , Cheng H. , Wang Y. , Yan M. , Bao Y.
Published: January 2021

Pan-Asian monsoon water isotope variability is found accompanied by a continental-scale hydroclimate footprint.
Glycolysis fuels phosphoinositide 3-kinase signaling to bolster T cell immunity
Authors: Xu Ke , Yin Na , Peng Min , Stamatiades Efstathios G. , Shyu Amy , Li Peng , Zhang Xian , Do Mytrang H. , Wang Zhaoquan , Capistrano Kristelle J. , Chou Chun , Levine Andrew G. , Rudensky Alexander Y. , Li Ming O.
Published: January 2021

A metabolic circuit in T cell immunity

Naïve T cells are metabolically reprogrammed when they differentiate into T effector (T
eff
) cells, transitioning from a reliance on mitochondrial oxidative phosphorylation to aerobic glycolysis. Xu
et al.
found that lactate dehydrogenase A (LDHA), a glycolytic enzyme that converts pyruvate to lactate, is a key player in this process. T
eff
cells that differentiate in mice infected with the bacterium
Listeria monocytogenes
turned on LDHA through phosphoinositide 3-kinase (PI3K) signaling. By promoting adenosine triphosphate (ATP) production, LDHA in turn facilitated PI3K-dependent inactivation of the transcription factor Foxo1 needed for effective T
eff
cell responses. Thus, glycolytic ATP acts like a rheostat that both gauges and regulates PI3K-dependent signaling. This type of positive feedback circuit may also provide a mechanistic explanation for the Warburg effect observed in cancer cells.

Science
, this issue p.
405
JARID2 and AEBP2 regulate PRC2 in the presence of H2AK119ub1 and other histone modifications
Authors: Kasinath Vignesh , Beck Curtis , Sauer Paul , Poepsel Simon , Kosmatka Jennifer , Faini Marco , Toso Daniel , Aebersold Ruedi , Nogales Eva
Published: January 2021

Cryo-EM uncovers polycomb interactions

Polycomb family enzymes include the chromatin modifiers PRC1 and PRC2, which are involved in gene repression. Although the catalytic functions of these complexes are well known, their functional relationship is not. Kasinath
et al.
used cryo–electron microscopy (cryo-EM) to visualize the interactions between nucleosomes containing ubiquitinated histone H2A, the product of PRC1, and the PRC2-activating cofactors JARID2 and AEBP2, providing the molecular basis for PRC1-dependent recruitment of PRC2. They also show that JARID2 and AEBP2 partially overcome the inhibitory effect of PRC2 by two trimethyl lysine transcription marks on histones. This work suggests that PRC2 regulation involves an intricate interplay between PRC2 cofactors and histone posttranslational modifications.

Science
, this issue p.
eabc3393
Regulation of the Dot1 histone H3K79 methyltransferase by histone H4K16 acetylation
Authors: Valencia-Sánchez Marco Igor , De Ioannes Pablo , Wang Miao , Truong David M. , Lee Rachel , Armache Jean-Paul , Boeke Jef D. , Armache Karim-Jean
Published: January 2021

Cross-talk between histone modifications

Histone modifications play pivotal roles within the intricate protein networks that underlie transcription and gene silencing in eukaryotic genomes. The enzymes that deposit them undergo spatiotemporal fine-tuning of their catalytic activity; one example is trans-histone cross-talk, in which one histone modification activates an enzyme responsible for another histone modification. Valencia-Sánchez
et al.
show that histone H4 lysine 16 acetylation (H4K16ac), a hallmark of decondensed, transcriptionally permissive chromatin, directly stimulates the Dot1 histone H3 lysine 79 methyltransferase. Structural, biochemical, and cellular data explain Dot1's regulation by H4K16ac and show how it coordinates with a second positive regulator of Dot1, histone H2B ubiquitination.

Science
, this issue p.
eabc6663
Clock genes and environmental cues coordinate
Anopheles
pheromone synthesis, swarming, and mating
Authors: Wang Guandong , Vega-Rodríguez Joel , Diabate Abdoulaye , Liu Jingnan , Cui Chunlai , Nignan Charles , Dong Ling , Li Fang , Ouedrago Cheick Oumar , Bandaogo Abdoul Malik , Sawadogo Péguédwindé Simon , Maiga Hamidou , Alves e Silva Thiago Luiz , Pascini Tales Vicari , Wang Sibao , Jacobs-Lorena Marcelo
Published: January 2021

Cuticular pheromone circadian regulation

Several species of anopheline mosquitoes are important malaria vectors in Africa. Male mosquitoes show species-specific swarming behaviors at certain times of the day to attract females for mating. Wang
et al.
found that transcriptional patterns of metabolic and immune function genes apparently showed a diurnal rhythm that correlated with the physiological demands of mating flight swarming (see the Perspective by Manoukis). By altering temperature and light regimes and by knocking out the master genes
period
and
timeless
for circadian clock regulation, the authors disrupted mating flight behavior in a combination of cage experiments and enclosed field conditions. Knocking out the rhythmically expressed desaturase enzyme reduced cuticular hydrocarbon pheromone production and limited mating success. These key interacting components of the diurnal regulation of mosquito mating behavior are potential targets for alternative malaria control strategies.

Science
, this issue p.
411
; see also p.
340
Unraveling CO adsorption on model single-atom catalysts
Authors: Hulva Jan , Meier Matthias , Bliem Roland , Jakub Zdenek , Kraushofer Florian , Schmid Michael , Diebold Ulrike , Franchini Cesare , Parkinson Gareth S.
Published: January 2021

Modeling single-atom reactivity

Noble metals often perform best for demanding reactions such as oxygen reduction, an effect often explained by the position of their d-band. One way to minimize the cost of noble metals is to disperse them as single atoms. To model the reactivity of supported single atoms, Hulva
et al.
evaporated different transition metals such as nickel, silver, and iridium on an Fe
3
O
4
(001) support. Single atoms adsorbed in the same twofold site between underlying rows of surface iron atoms. In studies of CO adsorption as a proxy for reactivity, the d-band was strongly affected by the charge transfer to the support and CO-induced structural changes. These effects can weaken the adsorption energy compared with the expected values based on electronic structure alone.

Science
, this issue p.
375
Rethinking immigration policies for STEM doctorates
Authors: Roach Michael , Skrentny John
Published: January 2021

Many Ph.D.'s follow an inefficient path to green cards through visas aimed at entry-level workers
Induction of Native c-di-GMP Phosphodiesterases Leads to Dispersal of Pseudomonas aeruginosa Biofilms
Authors: Andersen Jens Bo , Kragh Kasper Nørskov , Hultqvist Louise Dahl , Rybtke Morten , Nilsson Martin , Jakobsen Tim Holm , Givskov Michael , Tolker-Nielsen Tim
Published: January 2021

A decade of research has shown that the molecule c-di-GMP functions as a central second messenger in many bacteria. A high level of c-di-GMP is associated with biofilm formation, whereas a low level of c-di-GMP is associated with a planktonic single-cell bacterial lifestyle. c-di-GMP is formed by diguanylate cyclases and is degraded by specific phosphodiesterases.
pH-Induced Conformational Changes of Human Bocavirus Capsids
Authors: Luo Mengxiao , Mietzsch Mario , Chipman Paul , Song Kangkang , Xu Chen , Spear John , Sousa Duncan , McKenna Robert , Söderlund-Venermo Maria , Agbandje-McKenna Mavis
Published: January 2021

Human bocaviruses (HBoVs) are associated with disease in humans. However, the lack of an animal model and a versatile cell culture system to study their life cycle limits the ability to develop specific treatments or vaccines.
Comparison of Subgenomic and Total RNA in SARS-CoV-2-Challenged Rhesus Macaques
Authors: Dagotto Gabriel , Mercado Noe B. , Martinez David R. , Hou Yixuan J. , Nkolola Joseph P. , Carnahan Robert H. , Crowe James E. , Baric Ralph S. , Barouch Dan H.
Published: January 2021

Developing therapeutic and prophylactic countermeasures for the SARS-CoV-2 virus is a public health priority. During challenge studies, respiratory viruses are delivered and sampled from the same anatomical location.
Development of an intra-carbonate detachment during thrusting: The variable influence of pressure solution on deformation style, Khao Khwang Fold and Thrust Belt, Thailand
Authors: Morley C.K. , Jitmahantakul S. , von Hagke C. , Warren J. , Linares F.
Published: January 2021

Classic detachment zones in fold and thrust belts are generally defined by a weak lithology (typically salt or shale), often accompanied by high over-pressures. This study describes an atypical detachment that occurs entirely within a relatively strong Permian carbonate lithology, deformed during the Triassic Indosinian orogeny in Thailand under late diagenetic-anchimetamorphic conditions. The key differences between stratigraphic members that led to development of a detachment zone are bedding spacing and clay content. The lower, older, unit is the Khao Yai Member (KYM), which is a dark-gray to black, well-bedded, clay-rich limestone. The upper unit, the Na Phra Lan Member (NPM), comprises more massive, medium- to light-gray, commonly recrystallized limestones and marble. The KYM displays much tighter to even isoclinal, shorter-wavelength folds than the NPM. Pressure solution played a dominant role throughout the structural development—first forming early diagenetic bedding; later tectonic pressure solution preferentially followed this bedding instead of forming axial planar cleavage. The detachment zone between the two members is transitional over tens of meters. Moving up-section, tight to isoclinal folds with steeply inclined axial surfaces are replaced by folds with low-angle axial planes, thrusts, and thrust wedging, bed-parallel shearing, and by pressure solution along bedding-parallel seams (that reduce fold amplitude). In outcrops 100–300 m long, reduction of line-length shortening on folds from >50% to <10% shortening upwards indicates that deformation in the NPM is being accommodated differently from the KYM, probably predominantly by shortening on longer wavelength and/or spacing folds and thrusts, given the low amount of strain observed within the NPM, which excludes widespread layer-parallel thickening.
Role of sex and stature on the biomechanics of normal and loaded walking: implications for injury risk in the military
Authors: Gill Niamh , Roberts A , O'Leary T J , Liu A , Hollands K , Walker D , Greeves J P , Jones R
Published: January 2021

Load carriage and marching ‘in-step’ are routine military activities associated with lower limb injury risk in service personnel. The fixed pace and stride length of marching typically vary from thepreferredwalking gait and may result in overstriding. Overstriding increases ground reaction forces and muscle forces. Women are more likely to overstride than men due to their shorter stature. These biomechanical responses to overstriding may be most pronounced when marching close to thepreferredwalk-to-run transition speed. Load carriage also affects walking gait and increases ground reaction forces, joint moments and the demands on the muscles. Few studies have examined the effects of sex and stature on the biomechanics of marching and load carriage; this evidence is required to inform injury prevention strategies, particularly with the full integration of women in some defence forces. This narrative review explores the effects of sex and stature on the biomechanics of unloaded and loaded marching at a fixed pace and evaluates the implications for injury risk. The knowledge gaps in the literature, and distinct lack of studies on women, are highlighted, and areas that need more research to support evidence-based injury prevention measures, especially for women in arduous military roles, are identified.
Palliative care in Creutzfeldt-Jakob disease: looking back, thinking ahead
Authors: De Vries Kay , Cousins Emily , Harrison Dening Karen
Published: January 2021

Creutzfeldt-Jakob disease (CJD) is a rare and fatal neurodegenerative disease for which there is no cure. However, it is difficult to diagnose and is unique in that it is both a genetic and transmissible disease. The disease is characterised by symptoms of a rapidly progressive dementia. Palliation is the only treatment and early diagnosis is an important aspect in relation to gaining speedy access to palliative and end-of-life care services. People with CJD may be cared for in a diversity of settings including; general hospital wards, neurological units, hospices; care homes and in their own home. Management of physical and psychosocial symptoms and dealing with family bereavement is complex and challenging. Due to the complexity of the physical symptoms input from clinicians with palliative care expertise is an important consideration. Given transmission risk and the latent incidence of infection in the general population, following the emergence of variant CJD; plus the recent hypothesis of a potential relationship between immune responses to COVID-19 and the acceleration of preclinical or evident neurodegenerative disease, there is a need for renewed interest in research in this field. Over the past 20 years, many thousands of articles have been published on CJD. These have been predominately in the medical and science literature and very few publications have addressed the nursing care of persons and families dealing with CJD. There is a need for renewed interest in the management of the disease by supportive and palliative care services.
129 Interim evaluation of a clinical educators pilot study via a multi-stakeholder online survey
Authors: Huynh Chi , Hemavathi Muniswamy , Aiello Matthew , Clancy Mike , Kennedy Brian , Knox Jane , Phillips Eloise , Terry David , Khan Aanika , Rutherford Graham , Symons Helen , Chauhan Veena , England Health Education , Tam Christina
Published: January 2021

Aims/Objectives/Background

In England, the demand for emergency care is increasing, confounded by challenges with recruitment and retention of multi-professional teams in Emergency Departments (ED). The intense working environment that clinical ED staff face is recognised as a cause of staff dissatisfaction, attrition and premature career ‘burnout.’ A new ‘shop floor’ Clinical Educator (CE) role may improve the retention and wellbeing of multi-professional ED teams. A Health Education England pilot developed and recruited CEs across 54 acute trust EDs in England, from 2017. Aston University and the Royal College of Emergency Medicine were jointly commissioned to undertake a service benefit evaluation.

Methods/Design

An online survey was circulated to CEs, learners and managers across the 54 study sites. Each group answered questions relating to experiences, opinions and reflections. Topics included impact of a CE on patient flow, confidence and competence of staff, as well as sustainability and any impact on staff wellbeing.

Results/Conclusions

Results

314 individuals accessed the survey and 291 eligible respondents completed it, including: 187 learners, 65 CEs and 39 ED Clinical Directors/Managers.

Learners (169/187), CE (63/65) and managers (39/39) saw no change/an improvement in patient flow.

100% of CEs felt that a CE in the ED improved competence and confidence of staff (88.2% of learners, 89.7% of managers).

7% (61/65) of CEs and 87.2% (34/39) managers agree that CEs have improved wellbeing of staff.

8% of managers (26/39) were unsure whether the CE role would be funded beyond the pilot, but 66.7% (26/39) strongly supported continuation of the CE role.

Conclusion

Interim evidence suggests that CEs positively impact the multi-professional ED workforce.
185 A clinical risk score to identify patients with COVID-19 at high risk of critical care admission or death: An observational cohort study
Authors: Galloway James , Sneep Ruth , Cantle Fleur , Jina Raeesa , Brookes Andrew , Reid Carole , Sugarman Leah , Norton Sam
Published: January 2021

Aims/Objectives/Background

The COVID-19 pandemic continues to escalate. There is urgent need to stratify patients. Understanding risk of deterioration will assist in admission and discharge decisions, and help selection for clinical studies to indicate where risk of therapy-related complications is justified.

Methods/Design

An observational cohort of patients acutely admitted to two London hospitals with COVID-19 and positive SARS-CoV-2 swab results was assessed. Demographic details, clinical data, comorbidities, blood parameters and chest radiograph severity scores were collected from electronic health records. Endpoints assessed were critical care admission and death. A risk score was developed to predict outcomes.

Results/Conclusions

Analyses included 1,157 patients. Older age, male sex, comorbidities, respiratory rate, oxygenation, radiographic severity, higher neutrophils, higher CRP and lower albumin at presentation predicted critical care admission and mortality. Non-white ethnicity predicted critical care admission but not death. Social deprivation was not predictive of outcome. A risk score was developed incorporating twelve characteristics: age>40, male, non-white ethnicity, oxygen saturations<93%, radiological severity score>3, neutrophil count>8.0 x109/L, CRP>40 mg/L, albumin<34 g/L, creatinine>100 µmol/L, diabetes mellitus, hypertension and chronic lung disease. Risk scores of 4 or higher corresponded to a 28-day cumulative incidence of critical care admission or death of 40.7% (95% CI: 37.1 to 44.4), versus 12.4% (95% CI: 8.2 to 16.7) for scores less than 4.

Conclusion

Our study identified predictors of critical care admission and death in people admitted to hospital with COVID-19. These predictors were incorporated into a risk score that will inform clinical care and stratify patients for clinical trials.
198 Current provision of general practitioner services in or alongside emergency departments in England
Authors: Brant Heather , Voss Sarah , Cooper Alison , Edwards Michelle , Price Delyth , Gaughan James , Edwards Adrian , Benger Jonathan
Published: January 2021

Aims/Objectives/Background

One approach to addressing increasing demand in emergency departments (EDs) has been the co-location of general practitioners (GPs) in or alongside the emergency department (ED), known as GPED. This approach was both advocated by the National Health Service (NHS) and supported by capital funding in 2017. However, little is known about the models of GPED that have been implemented as a result.

Methods/Design

We collected data on the model of GPED in use (if any) at 163/177 (92%) of type one EDs in England at two time points: September 2017 and December 2019. Multiple data sources were used including: on-line surveys; interviews; case study data; publicly available information. Models were classified according to an iteratively developed taxonomy as Inside/integrated, Inside/parallel, Outside/onsite, Outside/offsite.

Results/Conclusions

The proportion of EDs using GPED increased from 81% to 95% over the study period. The most common model was ‘Inside/parallel’ to the ED: 30% (44/149) in 2017, rising to 49% (78/159) in 2019. The number of Inside/integrated models dropped from 26% (38/149) to 9% (15/159). 23 sites commenced and four sites ceased GPED provision. 87% (142/163) of the EDs sampled were awarded capital funding. We identified no association between the type of GPED model adopted and the observable characteristics of EDs such as annual attendance, rurality of location and deprivation within the population served.

The majority of EDs in England have now adopted GPED. The increase in Inside/parallel models and the reduction in Inside/integrated models is likely to be related to the availability of capital funding to finance structural changes to EDs so that separate GP services could be provided. Further research is required to understand the relative effectiveness of the various models of GPED identified.
109 Access to emergency health care in tiger reserves in the central Indian landscape. lessons for global emergency care
Authors: Trivedy Chet , Tate Vijaykumar , Kolhe Sheetal , Gadre Vishal , Andheria Anish
Published: January 2021

Aims/Objectives/Background

Forest staff working in remote locations are at high risk of life-threatening emergencies; including major trauma and snakebites. Timely access to appropriate emergency care is pivotal to life-saving treatment. This is the first study to systematically map public health facilities (PHFs) around tiger reserves (TRs) in central Indian state of Maharashtra.

Methods/Design

Using publically available data; GPS coordinates, medical staff, and services were identified for PHFs in increasing order of specialism; including Primary Healthcare Centre (PHC), Community Health Centre (CHC), Sub-district Hospital (SDH) and District Hospital (DH). GIS Network Analysis was used to identify the nearest PHFs in relation to the access points of eight TRs; and the shortest distance by road and corresponding travel time by vehicle were calculated.

Results/Conclusions

Of all PHFs, 87.5% offered basic emergency care, while only 54% offered radiology services. Of all trauma beds 99.9% were placed at DH level; along with 89% of all MBBS trained doctors. Only 28.6% of TR exit points had access to emergency ambulance service based within 30 minutes.

Abstract 109 Table 1

Average distance and time to access the nearest PHF

Type of Health Facility (n=96)Average distance from a TR access point to the nearest PHF in KilometersAverage time to reach the nearest PHF in minutes by a carPHC (38.5%)12.3 ± 8.6 (0.7–39.4) 24 ±17 (1–79) CHC (26%)24.9 ±12.4 (2.5–61.6) 47 ± 25 (5–123) SDH (13.5%)42 ±15.8 (4.7–80.9) 82 ± 32 (8–162) DH (22%)65.4 ± 28.9 (11.7–137.2) 126 ± 57 (23–235)

Conclusion

This study highlight the challenges of providing emergency healthcare in low- and middle-income countries and the urgent need for greater resources and infrastructure to support the delivery of emergency care for frontline forest staff in rural areas. Further work in progress to look at the provision of emergency care in remote settings.
468 Presentation of vulnerable children to ED during Lockdown: a concerning consequence of isolation
Authors: Asim Lalarukh , Jina Raeesa , Das Sreena
Published: January 2021

Aims/Objectives/Background

This study aims to evaluate changes to child safeguarding attendances to the emergency department (ED) during the lockdown period 1st of March till 31st May 2020 compared to the same time period in 2019.

The COVID-19 pandemic is the defining health crisis of our time and the first time firm social restrictions have been imposed since safeguarding practices have become embedded in the NHS. The NSPCC reported a large increase in contacts but there remain concerns that vulnerable children are invisible to agencies during this time.

Methods/Design

All children (< 18 years) who attended King’s College Hospital’s ED, and were reviewed in the weekly ED safeguarding meeting were included. Data was collected from electronic patient records for different parameters.

Results/Conclusions

The total number of children presenting via ED for safeguarding review fell from 865 in 2019 to 355 for the same period in 2020. However, the proportion requiring action by the hospital safeguarding team showed a significant increase (p= 1.5 x 10-4) suggesting the severity of cases during COVID-19 is worse.

The percentage of stabbings doubled (p=0.04) despite lockdown measures. This may be a contributor to the significant increase in referral to youth workers (p=8 × 10-4). The number of children attending who were considered high risk due to previous safeguarding concerns dropped by 75%.

As expected, the proportion of household injuries such as accidental ingestion and burns showed a significant increase (p=0.01 and p=0.002 respectively). The proportion of children from outside of our local boroughs was surprisingly higher in 2020 (p=0.03).

The findings show that the number of cases triggering a safeguarding review has dropped during lockdown and raises concerns about vulnerable children who remain hidden. The findings also suggest an increased severity of safeguarding presentations, supporting our fears that the implications of lockdown on vulnerable children is yet to be realised.
Sex differences in mapping and rhythm outcomes of a repeat atrial fibrillation ablation
Authors: Pak Hui-Nam , Park Je-Wook , Yang Song-Yi , Kim Min , Yu Hee Tae , Kim Tae-Hoon , Uhm Jae-Sun , Joung Boyoung , Lee Moon-Hyoung
Published: January 2021

Objective

The risk of procedure-related complications and rhythm outcomes differ between men and women after atrial fibrillation catheter ablation (AFCA). We evaluated whether consistent sex differences existed in mapping and rhythm outcomes in repeat ablation procedures.

Methods

Among 3282 patients in the registry, we analysed 443 consecutive patients (24.6% female, 58.5±10.3 years old, 61.5% with paroxysmal atrial fibrillation) who underwent a second AFCA. We compared the clinical factors, mapping, left atrial (LA) pressure, complications and long-term clinical recurrences after propensity score matching.

Results

LA volume index (43.1±18.6 vs 35.8±11.6 mL/m2, p<0.001) was higher, but LA dimension (40.0±6.8 vs 41.6±6.3 mm, p=0.018), LA voltage (0.94±0.55 vs 1.20±0.68 mV, p=0.002) and pericardial fat volume (89.5±43.1 vs 122.1±53.9 cm3, p<0.001) were lower in women with repeat ablation than in their male counterparts. Pulmonary vein (PV) reconnections were lower (58.7% vs 74.9%, p=0.001), but the proportion of extra-PV triggers (27.5% vs 17.0%, p=0.026) and elevated LA pulse pressures (79.7% vs 63.7%, p=0.019) was significantly higher in women than in men. There was no significant sex difference in the rate of procedure-related complications (4.6% vs 4.2%, p=0.791). During a 31-month (8–60) median follow-up, clinical recurrences were significantly higher in women after both the de novo procedure (log-rank p=0.039, antiarrhythmic drug (AAD)-free log-rank p<0.001) and the second procedure (log-rank p=0.006, AAD-free log-rank p=0.093). Female sex (HR 1.51, 95% CI 1.06 to 2.15, p=0.023), non-paroxysmal atrial fibrillation (HR 1.78, 95% CI 1.30 to 2.34, p<0.010) and extra-PV triggers (HR 1.88, 95% CI 1.28 to 2.75, p=0.001) were independently associated with clinical recurrences after repeat procedures.

Conclusions

During repeat AFCA procedures, PV reconnections were lower in women than in men, and the existence of extra-PV triggers and an LA pressure elevation were more significant, which resulted in poor rhythm outcomes.

Trial registration number

NCT02138695.
Biologic subtypes of melanoma predict survival benefit of combination anti-PD1+anti-CTLA4 immune checkpoint inhibitors versus anti-PD1 monotherapy
Authors: Rose April A N , Armstrong Susan M , Hogg David , Butler Marcus O , Saibil Samuel D , Arteaga Diana P , Pimentel Muniz Thiago , Kelly Deirdre , Ghazarian Danny , King Ian , Kamil Zaid Saeed , Ross Kendra , Spreafico Anna
Published: January 2021

Purpose

Anti-programmed cell death protein 1 (PD1)±anti-cytotoxic T-lymphocyte associated protein 4 (CTLA4) immune checkpoint inhibitors (ICIs) are standard therapeutic options for metastatic melanoma. We assessed whether biologic subtype according to primary tumor type or genomic subtype can function as predictive biomarkers for anti-PD1±anti-CTLA4 ICI in patients with advanced melanoma.

Methods

We performed a single-center retrospective cohort analysis of patients who received anti-PD1±anti-CTLA4 ICI for advanced melanoma between 2012 and 2019. Primary tumor type,BRAFandNRASmutation status, and other covariates were abstracted from chart review. Log-rank tests and multivariable Cox regression models were used to assess differences in clinical progression-free (cPFS) and overall survival (OS).

Results

We identified 230 patients who received 249 lines of anti-PD1±anti-CTLA4 ICI for unresectable or metastatic disease. Of these patients, 74% were cutaneous, 11% mucosal, 8% unknown primary and 7% acral.BRAFandNRASmutations were identified in 35% and 28% of patients, respectively. In multivariable analyses of the entire cohort, acral or mucosal primary tumor type, >3 metastatic sites, elevated LDH were predictive of shorter cPFS and OS. Combination ICI therapy was associated with longer cPFS (HR 0.57, 95% CI 0.38 to 0.86, p=0.007) and OS (HR 0.42, 95% CI 0.28 to 0.65, p<0.001). Combination ICI was significantly associated with longer OS in unknown primary and mucosal melanoma. There was a non-significant trend toward longer OS with anti-PD1+anti-CTLA4 in cutaneous melanoma, but not in acral melanoma. In multivariable analyses, combination ICI was associated with longer OS inNRAS(HR 0.24, 95% CI 0.10 to 0.62, p=0.003, n=69) andBRAFV600E/K (HR 0.47, 95% CI 0.24 to 0.90, p=0.024, n=86) mutant melanoma but notBRAF/NRASwild-type (n=94) melanoma.

Conclusions

In our cohort, primary melanoma tumor type and genomic subtype were independent predictive markers of cPFS and OS for patients with metastatic melanoma receiving anti-PD1 ICI. Primary tumor type and genomic subtype—including NRAS—should be further evaluated in prospective clinical trials to determine their value as predictive markers. Biologic subtypes may facilitate clinical decision-making when recommending combination ICI treatment (anti-PD1±anti-CTLA4) versus anti-PD1 alone for patients with metastatic melanoma.
Preclinical PET imaging with the novel human antibody89Zr-DFO-REGN3504 sensitively detects PD-L1 expression in tumors and normal tissues
Authors: Kelly Marcus P , Makonnen Sosina , Hickey Carlos , Arnold T Cody , Giurleo Jason T , Tavaré Richard , Danton Makenzie , Granados Christian , Chatterjee Ishita , Dudgeon Drew , Retter Marc W , Ma Dangshe , Olson William C , Thurston Gavin , Kirshner Jessica R
Published: January 2021

Background

Programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) blocking antibodies including cemiplimab have generated profound clinical activity across diverse cancer types. Tumorous PD-L1 expression, as assessed by immunohistochemistry (IHC), is an accepted predictive marker of response to therapy in some cancers. However, expression is often dynamic and heterogeneous, and therefore not reliably captured by IHC from tumor biopsies or archival samples. Thus, there is significant need for accurate whole-body quantification of PD-L1 levels.

Methods

We radiolabeled the novel human anti-PD-L1 antibody REGN3504 with zirconium-89 (89Zr) using the chelator p-SCN-Bn-Deferoxamine to enable non-invasive immuno-positron emission tomography (immuno-PET) of PD-L1 expression. PET imaging assessed the localization of89Zr-REGN3504 to multiple human tumor xenografts. Mice genetically humanized for PD-1 and PD-L1 were used to assess the biodistribution of89Zr-REGN3504 to normal tissues and the estimated human radiation dosimetry of89Zr-REGN3504 was also determined. Pharmacokinetics of REGN3504 was assessed in monkeys.

Results

Clear localization of89Zr-REGN3504 to human tumor xenografts was observed via PET imaging and ex vivo biodistribution studies demonstrated high (fourfold to sixfold) tumor:blood ratios.89Zr-REGN3504 specifically localized to spleen and lymph nodes in the PD-1/PD-L1 humanized mice.89Zr-REGN3504 immuno-PET accurately detected a significant reduction in splenic PD-L1 positive cells following systemic treatment with clodronate liposomes. Radiation dosimetry suggested absorbed doses would be within guidelines for other89Zr radiolabeled, clinically used antibodies. Pharmacokinetics of REGN3504 was linear.

Conclusion

This work supports the clinical translation of89Zr-REGN3504 immuno-PET for the assessment of PD-L1 expression. Future clinical studies will aim to investigate the utility of89Zr-REGN3504 immuno-PET for predicting and monitoring response to anti-PD-1 therapy.
Changes in emotions and perceived stress following time spent in an artistically designed multisensory environment
Authors: Cavanagh Bliss , Haracz Kirsti , Lawry Miranda , Wales Kylie , James Carole
Published: January 2021

Self-management strategies that enhance positive emotions are considered most effective to cope with stress and maintain good mental health and well-being. An artistically designed multisensory environment, The Sensory-Art Space (SAS), was installed in a university in NSW Australia as a new self-management intervention. The design of the SAS was informed by evidence regarding the benefits of viewing art, experiencing nature and accessing sensory rooms.

A pilot pre–post intervention study measured changes in affect and perceived stress in 224 participants who spent time in the SAS. Descriptive statistics were completed on the individual affective states, and paired sample t-tests were used to determine changes in Positive and Negative Affect (PANAS-X) and perceived stress (Visual Analogue Scale).

The Wilcoxon signed-rank test showed that negative affect reduced, z=−10.23 (p<0.001), and positiveaffect increased, z=−2.57 (p=0.01), following spending time in the SAS. In addition, stress levels reduced after time spent in the SAS, z=−11.29 (p<0.0001).

Self-management benefits were found following time in the SAS and future implications for public health and well-being are discussed.
Experimental evaluation of direct thromboaspiration efficacy according to the angle of interaction between the aspiration catheter and the clot
Authors: Bernava Gianmarco , Rosi Andrea , Boto José , Hofmeister Jeremy , Brina Olivier , Reymond Philippe , Muster Michel , Yilmaz Hasan , Kulcsar Zsolt , Carrera Emmanuel , Bouri Mohamed , Lovblad Karl-Olof , Machi Paolo
Published: January 2021

Background

Successful direct thromboaspiration (DTA) is related to several factors such as clot consistency, size, and location. It has also been demonstrated recently that the angle of interaction (AOI) formed by the aspiration catheter and the clot is related to DTA efficacy. The aims of this study were three-fold: (a) to confirm the clinical finding that the AOI formed by the aspiration catheter and the clot influence DTA efficacy; (b) to evaluate to what extent this influence varies according to differences in clot consistency and size; and (c) to validate stent retriever thrombectomy as an effective rescue treatment after DTA failure in the presence of an unfavorable AOI.

Methods

A rigid vascular phantom designed to reproduce a middle cerebral artery trifurcation anatomy with three M2 segments forming different angles with M1 and thrombus analog of different consistencies and sizes was used.

Results

DTA was highly effective for AOIs >125.5°, irrespective of thrombus analog features. However, its efficacy decreased for acute AOIs. Rescue stent retriever thrombectomy was effective in 92.6% of cases of DTA failure.

Conclusions

This in vitro study confirmed that the AOI formed by the aspiration catheter and the thrombus analog influenced DTA efficacy, with an AOI >125.5° related to an effective DTA. Stent retriever thrombectomy was an effective rescue treatment after DTA failure, even in the presence of an unfavorable AOI.
Geometric variations associated with posterior communicating artery aneurysms
Authors: Zhang Jian , Can Anil , Lai Pui Man Rosalind , Mukundan, Jr. Srinivasan , Castro Victor M , Dligach Dmitriy , Finan Sean , Gainer Vivian , Shadick Nancy , Savova Guergana , Murphy Shawn N , Cai Tianxi , Weiss Scott T , Du Rose
Published: January 2021

Background

Hemodynamic stress, conditioned by the morphology of the surrounding vasculature, plays an important role in aneurysm formation. Our goal was to identify image-based location-specific parameters that are associated with posterior communicating artery (PCoA) aneurysms.

Methods

Three-dimensional morphological parameters obtained from CT angiography or digital subtraction angiography from 187 patients with unilateral PCoA aneurysms, diagnosed at the Brigham and Women’s Hospital and Massachusetts General Hospital between 1990 and 2016, were evaluated. In order to control for genetic and clinical risk factors, we chose the contralateral unaffected PCoA as a control group. We examined diameters and angles of the surrounding parent and daughter vessels. Univariable and multivariable statistical analyses were performed to determine statistical significance. Sensitivity analyses with small aneurysms (≤5 mm) only and an unmatched analysis of 432 PCoA aneurysms and 197 control patients without PCoA aneurysms were also performed.

Results

In a multivariable conditional logistic regression model we showed that smaller diameter size ratio (OR 1.45×10−5, 95% CI 1.12×10−7to 1.88×10−3) and larger daughter-daughter angle (OR 1.04, 95% CI 1.02 to 1.07) were significantly associated with PCoA aneurysm presence after correcting for other variables. In subgroup analyses of small aneurysms (≤5 mm) and in an unmatched analysis the significance and direction of these results were preserved.

Conclusions

Larger daughter-daughter angles and smaller diameter size ratio are significantly associated with the presence of PCoA aneurysms. These simple parameters can be utilized to guide the risk assessment for the formation of PCoA aneurysms in high risk patients.
Association of device type, flavours and vaping behaviour with tobacco product transitions among adult electronic cigarette users in the USA
Authors: Harlow Alyssa F , Fetterman Jessica L , Ross Craig S , Robertson Rose Marie , Bhatnagar Aruni , Benjamin Emelia J , Stokes Andrew C
Published: January 2021

Background

Few studies assess whether electronic cigarette (e-cigarette) device characteristics or flavours impact longitudinal patterns of cigarette and e-cigarette use.

Design

We examined data from waves 2–4 of the Population Assessment of Tobacco and Health Study (2014–2018). Among adult (≥18 years) current e-cigarette users at wave 2 who were current smokers (dual users; n=1759) and former smokers (exclusive e-cigarette users; n=470), we classified participants into four use patterns at wave 3 (~12 months later) and wave 4 (~24 months later): (1) dual use of e-cigarettes and cigarettes; (2) exclusive cigarette smoking; (3) exclusive e-cigarette use; (4) non-use of both products. We used multinomial logistic regression to assess correlates of changing use patterns at 24 months, relative to no change, adjusting for sociodemographic factors.

Results

At 24 months, 26.5% of baseline exclusive e-cigarette users, and 9% of baseline dual users, abstained from both vaping and smoking. Participants who vaped non-tobacco flavours (vs tobacco flavours), and used refillable tank or modifiable devices (vs disposable, cartridges and other devices) were less likely to transition to non-use of both products and to exclusive cigarette smoking. Baseline daily vaping (vs non-daily) was positively associated with exclusive e-cigarette use at 24 months for baseline daily cigarette smokers, but negatively associated with exclusive e-cigarette use and non-use of both products at 24 months for baseline non-daily smokers.

Conclusions

Non-tobacco flavours, daily vaping and modifiable e-cigarette devices may help some smokers abstain from cigarette smoking via transitioning to exclusive e-cigarette use, but are also associated with ongoing exclusive e-cigarette use.