bluuebunny/crossref_metadata_2025 huggingface dataset:
Spray‐dried plasma: A post‐traumatic blood “bridge” for life‐saving resuscitation
Authors: Popovsky Mark A. , White Nathan
Published: July 2021

Massive bleeding remains a major source of morbidity and mortality worldwide. Recent studies have shed light on the pathophysiology of traumatic‐induced coagulopathy and the central role of endotheliopathy. Transfusion therapy has changed dramatically in the last decade with use of red cells and plasma in a 1:1 ratio. The use of early transfusion increases the likelihood of a favorable outcome. Early intervention‐preferably less than 60 min of injury‐is a major factor in improved survival. Experience with dried plasma products—lyophilized or freeze‐dried—in Europe and South Africa has demonstrated both safety and efficacy. Dry plasma products are not available in the United States but several products are in development. Spray‐dried plasma contains clinically meaningful levels of coagulation activity and in vitro data suggest robust ability to generate thrombus. The decentralized, blood‐center based manufacturing model of spray‐dried plasma offers advantages for availability to meet routine and extraordinary demands.
Cold‐stored leukoreduced whole blood: Extending the time between donation and filtration has minimal impact on in vitro quality
Authors: Schubert Peter , Chen Zhongming , Bhakta Varsha , Culibrk Brankica , Wambolt Richard , Sheffield William P. , Devine Dana V. , McTaggart Ken
Published: July 2021

Background

Leukoreduced whole blood (LR‐WB) has received renewed attention as alternative to component‐based transfusion in trauma. According to the manufacturer's instructions, leukoreduction should be carried out within 8 h after collection. This study assessed impact of (1) WB collection bag, (2) LR filtration, and (3) timing of filtration on in vitro quality.

Study Design and Methods

WB collected into different vendor bags was held at room temperature for <8 h or >16 h but <24 h prior to LR. In vitro quality was assessed before and after filtration, and throughout 3 weeks of storage at 4°C. Cell count and hemoglobin levels were determined by hematology analyzer, platelet activation, and responsiveness to ADP by surface expression of P‐selectin by flow cytometry, hemolysis by HemoCue, and metabolic parameters by blood gas analyzer. Hemostatic properties were assessed by rotational thromboelastometry. Plasma protein activities and clotting times were determined by automated coagulation analyzer or quantitative immunoblotting.

Results

Bag type had no impact on WB in vitro quality. LR by filtration had some impact, but is aligned with data in the literature. The time between donation and filtration resulted in some statistically significant differences in metabolic activity, platelet yield, platelet activation, and factor protein activity initially; however, these differences in in vitro quality attributes decreased throughout 21‐day cold storage.

Conclusion

WB hold time showed only a minor impact on WB in vitro quality, so it may be possible for blood processing facilities to explore extended hold times prior to filtration in order to provide greater operational flexibility.
Hipertensión Arterial, Diabetes Mellitus y factores de riesgo cardiovasculares en trabajadores de una plaza de mercado de un municipio de Antioquia, Colombia, 2017-2018
Authors: Vasquez Daniel , Garzón Duque María Osley
Published: July 2021

Introducción. Enfermedades como la diabetes mellitus y la hipertensión arterial son cada vez más frecuentes a nivel mundial con importantes costos sociales asociados. Objetivo. Evaluar la prevalencia de hipertensión y diabetes en los trabajadores de la plaza de mercado de un municipio de Antioquia, Colombia y los factores de riesgo asociados. Metodología. Se llevó a cabo un estudio observacional de tipo transversal analítico en un censo de 194 trabajadores de los cuales 152 tuvieron evaluación médico-laboral y encuesta de datos sociodemográficos y laborales. Se hizo una estandarización previa de los evaluadores con control de calidad del dato y análisis univariado y bivariado de los datos con IC 95%. Resultados. El 57% era mujer, 73,4% ganaba menos de un salario mínimo mensual legal vigente, 65,8% laboraba entre 9 y 12 horas y 11,9% entre 13 y 18 horas al día. El 62,4% no realizaba actividad física y 67,0% prefería los alimentos fritos. Un 20,9% tenía hipertensión arterial y se asoció con el estado civil, edad, antigüedad en el oficio, presión sistólica al momento de la evaluación, antecedente familiar y sexo. Un 9,2% tenía diabetes mellitus y esto se asoció con el estado civil, edad y presión sistólica al momento de la evaluación. Conclusiones. Se encuentra una población trabajadora informal con alta carga de enfermedad y de factores de riesgo que evidencian la necesidad de políticas públicas y programas enfocados específicamente en sus riesgos y estilos de vida.
The Unified Theory of Tubesheet Design—Part II: Supplement to the Theoretical Analysis
Authors: Zhu Hong-Song , Zhai Jinguo
Published: July 2021

The theoretical foundation of the unified theory of tubesheet (TS) design for fixed TS heat exchangers (HEXs), floating head, and U-tube HEXs are presented in Part I, in which only the most important equations are addressed to show the main points of the theory. The equations, conclusions, and other aspects referenced in Part I are presented or proved in this paper as Part II to supplement the theoretical analysis in Part I.
Multiobjective Optimization of a Novel Solar Tower-Based Gas Turbine-Driven Multi-Generation Plant With Energy, Exergy, Economic, and Environmental Impact Analysis
Authors: Colakoglu Mert , Durmayaz Ahmet
Published: July 2021

In this study, a novel solar tower-based gas turbine-driven multi-generation plant is proposed and analyzed in detail with energy, exergy, economic, and environmental impact analysis. A multiobjective optimization is performed by incorporating all performance indicators simultaneously. The proposed plant consists of an intercooling-regenerative-reheat solarized gas turbine cycle as the primary power cycle of a multi-generation plant for the first time. Two organic Rankine cycles are used to utilize waste heat of intercooling section and exhaust of gas turbine. To produce the multi-generation products of power, cooling, industrial process heating, fresh water, floor heating, green hydrogen, domestic hot water, hot air for food drying, and greenhouse heating, power cycles are integrated with a multi-effect desalination, a double-effect absorption refrigeration cycle, an electrolyzer, a drying hot air unit, a greenhouse heater, and an industrial process heater. A rigorous parametric analysis is performed to reveal the effects of variations of decision variables on the plant performance. At the optimum conditions, energy efficiency, exergy efficiency, average unit product exergy cost, and emission savings values are determined as 57.23%, 40.7%, 0.08315 $/kWh, and 948.7 kg CO2/h, respectively. Moreover, proposed plant can produce 1962 kW power and 3.353 kg/h hydrogen in addition to other utilities with a system cost rate of 0.05134 $/s and 3226 kW exergy destruction rate.
Three-Dimensional Simulation of Vapor Bubble Growth in Superheated Water Due to the Convective Action by an Interface Tracking Method
Authors: Sharif Syed Ahsan , Ho Mark Kai Ming , Timchenko Victoria , Yeoh Guan Heng
Published: July 2021

In this paper, the growth of a rising vapor bubble in superheated water was numerically studied using an advanced interface tracking method, called the intersection marker (ISM) method. The ISM method is a hybrid Lagrangian–Eulerian front-tracking algorithm that can model an arbitrary three-dimensional (3D) surface within an array of cubic control volumes (CCV). The ISM method has cell-by-cell remeshing capability that is volume conservative, maintains surface continuity, and is suited for tracking interface deformation in multiphase flow simulations. This method was previously used in adiabatic bubble rise simulation with no heat and mass transfers to or from the bubble were considered. This work will extend the ISM method's application to simulate vapor bubble growth in superheated water with the inclusion of additional physics, such as the convective heat transfer mechanism and the phase-change. Coupled with an in-house variable-density and variable-viscosity single-fluid flow solver, the method was used to simulate vapor bubble growth due to the convective action. The forces such as the surface tension and the buoyancy were included in the momentum equation. The source terms for the mass transfer were also modeled in the computational fluid dynamics governing equations to simulate the growth. Bubble properties such as size, shape, velocity, drag coefficient, and convective heat transfer coefficient were predicted. Effects of surface tension and temperature on the bubble characteristic were also discussed. Obtained numerical results were compared against the analytical and past works and found to be in good agreement.
Patterns and Reduced-Order Reconstruction of Impinging Wiping Jet Pressure Profile Fluctuation Using Proper Orthogonal Decomposition
Authors: Phan Le Quang , Johnstone Andrew D. , Kosasih Buyung , Renshaw Wayne
Published: July 2021

Wiping jet impingement pressure is important in controlling the coating mass (thickness) and influencing the smoothness of the thin metallic coating produced in continuous galvanizing lines (CGLs). However, the fluctuation of the impingement pressure profile that directly impacts the coating smoothness has not been adequately understood. To study key features of the impingement pressure fluctuation, the instantaneous impingement pressure profiles obtained from large eddy simulations (LES) were analyzed using proper orthogonal decomposition (POD). Dominant fluctuation modes of pressure profiles can be differentiated based on the energy contents of the modes corresponding to different jet types, namely, mixing, nonmixing, and transitional mixing jet. The dominant modes of mixing jets in the wiping region contain comparable strength of all modes (flapping, pulsing, and out-of-phase multipulsing). Nonmixing jets do not show discernable fluctuation modes, and transitional mixing jets show pulsing and flapping modes only. Additionally, instantaneous maximum pressure gradients and their locations were determined from the reduced-order reconstructions of the pressure profiles. From the analysis, frequency spectra of the magnitude and location fluctuations of the maximum pressure gradients associated with each of the jet types can be clearly distinguished. This is the knowledge that may be helpful for CGL operators in the operation of wiping jets.
Cracking Pattern of Indented Ice Sheet Bending Failures
Authors: Xu Ning , Zhang Haisheng , Wang Yihe
Published: July 2021

Ice sheet bending failures have been investigated extensively for ice loads on conical offshore structures and icebreakers in arctic regions. Most previous theoretical studies focus on bending failures of semi-infinite level ice, ice wedges, or finite-sized rectangular ice floes. For indented ice sheet bending failures, analytical ice load models have been developed by assuming a radial-before-circumferential cracking pattern. Recently, real-time simulations of ice-structure interactions are gaining increasing traction due to their great application potential. The analytical or semi-analytical models implemented into the real-time simulator significantly influence the accuracy of real-time simulations. Against this backdrop, the cracking pattern assumption needs to be more critically examined, and the criterion for cracking pattern determinations is in demand for utilizing different models for different cracking patterns in real-time simulations. Motivated by this need, the current paper establishes the cracking pattern determination criterion for indented ice sheet bending failures, based on the theory of plates on elastic foundations and normalized formulae. It is found that large indentation lengths and radii of structure waterline curvature induce a circumferential-before-radial cracking pattern. Conversely, small indentation lengths and radii of structure waterline curvature result in a radial-before-circumferential cracking pattern.
A New Method for Prediction of the Acoustic Performance and Design Parameter Sensitivity Analysis of Multi-Chamber Perforated Resonators With an Irregular Cross Section
Authors: Guo Rong , Sun Zanzan , Huang Zhen , Luo Rui
Published: July 2021

Aiming at reducing the high-amplitude and wide-frequency noise in charged air intake system of the powertrain, this paper proposes a new method for predicting the acoustic characteristics of an irregular cross-section multi-chamber perforated resonator under flow conditions. By this method, the presence of three-dimensional sound waves and the effects of higher-order modes are considered, and the acoustic performance of the resonator can be evaluated through the computation of transmission loss. Moreover, by discretizing the cross-section of the perforated resonator and extracting node information, this method can solve the acoustic characteristics of the perforated resonator with any cross section. Based on the transfer matrix method, the quadrupole parameters of each chamber are obtained. Then, the acoustic characteristics of the multi-chamber perforated resonator could be calculated. The theoretical prediction data and the experimental data have been compared, and the results show good agreement within the entire frequency range, which verifies the accuracy of the theoretical prediction approach. Based on this prediction approach, the influence of section ratio, structure parameters, and inlet flowrate on the acoustic characteristics of the resonator is explored. The results show that when the structural parameters change, the peak resonance frequency of the resonator will have a regular shift. With the increase of the inlet flowrate, the main frequency band of sound attenuation will decrease significantly. The theoretical method developed in this work can be used for the calculation and optimization of multi-chamber resonators in various applications.
Early Specialization and Critical Periods in Acquiring Expertise: A Comparison of Traditional Versus Detection Talent Identification in Team GB Cycling at London 2012
Authors: Staff Toby , Gobet Fernand , Parton Andrew
Published: July 2021

The aim of this study was to compare two methodologies employed by the British Cycling talent identification program. Specifically, the authors investigated cyclists selected to represent GB cycling team at the London 2012 Olympics using (a) a traditional talent identification methodology (British Cycling Olympic Development Program), where selection is based upon race results and (b) a detection talent identification methodology (U.K. Sport Talent Team Program), which is a multi-Olympic event initiative that identifies athletic potential from physical and skill-based tests. To facilitate this comparison, the authors calculated the speed with which expertise was acquired. A Mann–WhitneyUtest (U = 16.0,p = .031) indicated that the speed of acquiring expertise was quicker in detection talent identification (Mdn = 5.4) than traditional talent identification (Mdn = 7.2). Practice started later with detection talent identification than with traditional talent identification (14.12 years vs. 11.23 years, respectively), which affected the period to excellence. Thus, detection talent identification resulted in an absence of early specialization, which suggests a critical period for attaining cycling expertise. The authors hypothesize a genetic basis of talent and propose that critical periods are important in detection talent identification programs.
An ancestral recombination graph of human, Neanderthal, and Denisovan genomes
Authors: Schaefer Nathan K. , Shapiro Beth , Green Richard E.
Published: July 2021

A new heuristic ARG inference tool maps archaic hominin admixture and highlights genomic regions unique to modern humans.
Noninvasive quantitative assessment of collagen degradation in parchments by polarization-resolved SHG microscopy
Authors: Schmeltz Margaux , Robinet Laurianne , Heu-Thao Sylvie , Sintès Jean-Marc , Teulon Claire , Ducourthial Guillaume , Mahou Pierre , Schanne-Klein Marie-Claire , Latour Gaël
Published: July 2021

Conservation state of medieval parchments is noninvasively assessed by advanced quantitative nonlinear optical microscopy.
Analog memristive synapse based on topotactic phase transition for high-performance neuromorphic computing and neural network pruning
Authors: Mou Xing , Tang Jianshi , Lyu Yingjie , Zhang Qingtian , Yang Siyao , Xu Feng , Liu Wei , Xu Minghong , Zhou Yu , Sun Wen , Zhong Yanan , Gao Bin , Yu Pu , Qian He , Wu Huaqiang
Published: July 2021

Memristor with topotactic phase transition demonstrates controllable analog switching and implements neural network pruning.
Systematic review of ecological momentary assessment (EMA) studies of five public health-related behaviours: review protocol
Authors: Kwasnicka Dominika , Kale Dimitra , Schneider Verena , Keller Jan , Yeboah-Asiamah Asare Bernard , Powell Daniel , Naughton Felix , ten Hoor Gill A , Verboon Peter , Perski Olga
Published: July 2021

Introduction

Ecological momentary assessment (EMA) involves repeated, real-time assessments of phenomena (eg, cognitions, emotions, behaviours) over a period of time in naturalistic settings. EMA is increasingly used to study both within-person and between-person processes. We will review EMA studies investigating key health behaviours and synthesise: (1) study characteristics (eg, frequency of assessments, adherence, incentives), (2) associations between psychological predictors and behaviours and (3) moderators of adherence to EMA protocols.

Methods and analysis

This review will focus on EMA studies conducted across five public health behaviours in adult, non-clinical populations: movement behaviour (including physical activity and sedentary behaviour), dietary behaviour, alcohol consumption, tobacco smoking and preventive sexual health behaviours. Studies need to have assessed at least one psychological or contextual predictor of these behaviours. Studies reporting exclusively on physiological outcomes (eg, cortisol) or those not conducted under free-living conditions will be excluded. We will search OVID MEDLINE, Embase, PsycINFO and Web of Science using terms relevant to EMA and the selected health behaviours. Reference lists of existing systematic reviews of EMA studies will be hand searched. Identified articles will be screened by two reviewers. This review is expected to provide a comprehensive summary of EMA studies assessing psychological or contextual predictors of five public health behaviours.

Ethics and dissemination

The results will be disseminated through peer-reviewed publications and presentations. Data from included studies will be made available to other researchers. No ethics are required.

PROSPERO registration number

CRD42020168314.
Longitudinal pre-exposure prophylaxis (PrEP) acceptability, initiation and adherence among criminal justice-involved adults in the USA: the Southern PrEP Cohort Study (SPECS) protocol
Authors: LeMasters Katherine , Oser Carrie , Cowell Mariah , Mollan Katie , Nowotny Kathryn , Brinkley-Rubinstein Lauren
Published: July 2021

Introduction

HIV prevalence among criminal justice (CJ)-involved adults is five times higher than the general population. Following incarceration, CJ-involved individuals experience multilevel barriers to HIV prevention. Pre-exposure prophylaxis (PrEP) is a widely available, daily medication efficacious in preventing HIV. Little is known about PrEP knowledge, acceptability, initiation and sustained use among CJ-involved persons or about how these outcomes vary by multilevel factors. The Southern Pre-Exposure Prophylaxis Study (SPECS) will investigate barriers and facilitators for PrEP initiation and sustained use among CJ-involved adults, building a foundation for PrEP interventions for this underserved population.

Methods and analysis

SPECS uses a mixed-methods sequential design, including a multisite, prospective cohort study in three southern states—North Carolina, Florida and Kentucky—and subsequent qualitative interviews. HIV-negative adults clinically indicated for PrEP with CJ-involvement in the past year (n=660; 220 per site)—will be recruited for four quantitative interviews separated by 6 months, with 18 months of follow-up. Interviews will measure CJ involvement, substance use, sexual behaviours, PrEP acceptability and use, healthcare access and utilisation, support systems and psychological and emotional well-being. We will estimate probabilities of PrEP acceptability and use in a CJ-involved population using descriptive and multivariable analyses. After the follow-up, a subsample that never initiated PrEP, initiated but did not sustain PrEP or sustained PrEP will be asked to participate in a qualitative interview to contextualise their experiences and decisions around PrEP. An inductive approach will guide qualitative analyses.

Ethics and dissemination

PrEP initiation and sustained use rates are unknown among CJ-involved adults. This research will identify individual, social and structural factors that predict PrEP initiation and use. Data generated from the study have the potential to guide research and the development and tailoring of PrEP interventions to CJ-involved populations and provide context to HIV-related outcomes for those with CJ experiences.
Quality of care for peripheral intravenous catheters (PIVCs) in Nepal: a cross-sectional study on feasibility and inter-rater agreement of the Peripheral Intravenous Catheters-mini Questionnaire (PIVC-miniQ) in a tertiary care hospital
Authors: Shrestha Sulekha , Vieler Johannes , Haug Nikolai Juliussen , Afset Jan Egil , Høvik Lise Husby , Lydersen Stian , Gustad Lise Tuset
Published: July 2021

Objectives

There is a lack of data regarding the quality of peripheral intravenous catheter (PIVC)-related care from low-income and middle-income countries, even though the use of PIVCs may lead to local or severe systemic infections. Our main objective was to assess the feasibility and inter-rater agreement on the PIVC-mini Questionnaire (PIVC-miniQ) in a tertiary care hospital in Nepal.

Design

We performed an observational cross-sectional quantitative study using the PIVC-miniQ to collect information on PIVC quality.

Setting

Secondary care in a Nepalese hospital. All patients with PIVCs in selected wards were included in the study and PIVCs were assessed independently by two raters. Eight Nepalese nurses, one Nepalese student and three Norwegian students participated as raters.

Primary and secondary outcome measures

The intraclass correlation coefficient (ICC), positive, negative, absolute agreement, Scott’s pi and sum score were calculated using PIVC-miniQ. We also aimed to describe PIVC quality of care, as it is important to prevent PIVC-associated complications such as phlebitis or catheter-associated bloodstream infections.

Results

A total of 390 patients (409 PIVCs) were included in the study. The ICC between raters was 0.716 for Nepalese raters, 0.644 for Norwegian raters and 0.481 for the pooled data. The most frequently observed problems associated with PIVCs were blood in the intravenous line (51.5%), pain and tenderness on palpation (43.4%), and fixation with opaque tape (38.5%). The average sum score was 3.32 deviations from best practice for PIVCs fixed with non-sterile opaque tape and 2.37 for those fixed with transparent dressing (p<0.001).

Conclusion

The PIVC-miniQ is a feasible and reliable tool for nurses assessing PIVC quality in hospitalised patients in Nepal. The study revealed gaps in PIVC quality and care that could be improved by providing transparent PIVC dressings for all patients and requiring all PIVC insertions to be documented in patient charts.
Mediating role of coping styles on anxiety in healthcare workers victim of violence: a cross-sectional survey in China hospitals
Authors: Ma Yuanshuo , Wang Yongchen , Shi Yu , Shi Lei , Wang Licheng , Li Zhe , Li Guoqiang , Zhang Yafeng , Fan Lihua , Ni Xin
Published: July 2021

Objective

The purposes of this study were to evaluate the rate of workplace violence in county hospitals in China and its impact on healthcare workers and to explore the relationship between hospital violence, coping styles and anxiety to provide effective procedures for reducing anxiety among healthcare workers.

Methods

The study used stratified sampling to select 1200 healthcare workers from 30 county hospitals in China to conduct a questionnaire survey. Of these, 1030 were valid questionnaires, and the effective response rate was 85.83%. We collected demographic characteristics of our participants and administered the following scales to them: Workplace Violence, Trait Coping Style, Self-rating Anxiety. Data were statistically analysed.

Results

The results showed that 67.28% of healthcare workers in county hospitals in China had experienced workplace violence in the previous 12 months, with prevalent verbal violence (66.12%) followed by physical violence (15.24%). Workplace violence in hospitals was negatively related to positive coping (r=−0.091, p<0.01) but positively related to negative coping (r=0.114, p<0.001) and anxiety (r=0.298, p<0.001). Positive and negative coping was negatively (r=−0.085, p<0.01) and positively (r=0.254, p<0.001) associated with anxiety respectively. Positive and negative coping influenced both hospital workplace violence and anxiety in healthcare workers who were victims of violence. Compared with positive coping, the mediating effect of negative coping was stronger (95% CI −0.177 to –0.006).

Conclusions

The incidence of workplace violence among healthcare workers in county-level hospitals in China is relatively high, and there is a correlation between hospital violence, coping styles and anxiety. Positive and negative coping play a mediating role in the impact of hospital violence on healthcare workers’ anxiety. Therefore, hospital administrators should actively promote healthcare workers’ transition to positive coping strategies and minimise the negative impact of anxiety on them.
Cross-sectional study of preprints and final journal publications from COVID-19 studies: discrepancies in results reporting and spin in interpretation
Authors: Bero Lisa , Lawrence Rosa , Leslie Louis , Chiu Kellia , McDonald Sally , Page Matthew J , Grundy Quinn , Parker Lisa , Boughton Stephanie , Kirkham Jamie J , Featherstone Robin
Published: July 2021

Objective

To compare results reporting and the presence of spin in COVID-19 study preprints with their finalised journal publications.

Design

Cross-sectional study.

Setting

International medical literature.

Participants

Preprints and final journal publications of 67 interventional and observational studies of COVID-19 treatment or prevention from the Cochrane COVID-19 Study Register published between 1 March 2020 and 30 October 2020.

Main outcome measures

Study characteristics and discrepancies in (1) results reporting (number of outcomes, outcome descriptor, measure, metric, assessment time point, data reported, reported statistical significance of result, type of statistical analysis, subgroup analyses (if any), whether outcome was identified as primary or secondary) and (2) spin (reporting practices that distort the interpretation of results so they are viewed more favourably).

Results

Of 67 included studies, 23 (34%) had no discrepancies in results reporting between preprints and journal publications. Fifteen (22%) studies had at least one outcome that was included in the journal publication, but not the preprint; eight (12%) had at least one outcome that was reported in the preprint only. For outcomes that were reported in both preprints and journals, common discrepancies were differences in numerical values and statistical significance, additional statistical tests and subgroup analyses and longer follow-up times for outcome assessment in journal publications.

At least one instance of spin occurred in both preprints and journals in 23/67 (34%) studies, the preprint only in 5 (7%), and the journal publications only in 2 (3%). Spin was removed between the preprint and journal publication in 5/67 (7%) studies; but added in 1/67 (1%) study.

Conclusions

The COVID-19 preprints and their subsequent journal publications were largely similar in reporting of study characteristics, outcomes and spin. All COVID-19 studies published as preprints and journal publications should be critically evaluated for discrepancies and spin.
Individualized genetic makeup that controls natural killer cell function influences the efficacy of isatuximab immunotherapy in patients with multiple myeloma
Authors: Sun Haibo , Martin Thomas G , Marra John , Kong Denice , Keats Jonathon , Macé Sandrine , Chiron Marielle , Wolf Jeffrey L , Venstrom Jeffrey M , Rajalingam Raja
Published: July 2021

Background

Phase IIb clinical trial with isatuximab (Isa)-lenalidomide (Len)-dexamethasone (Dex) showed an improved progression-free survival (PFS) in patients with relapsed or refractory multiple myeloma (RRMM), but the efficacy varied by patient. Antibody-dependent cell-mediated cytotoxicity (ADCC) by natural killer (NK) cells plays a crucial role in arbitrating antitumor activities of therapeutic-antibodies. We tested if patient-specific genetic makeup known to set NK cell functional threshold influence response to Isa-Len-Dex therapy.

Methods

We characterized 57 patients with RRMM receiving Isa-Len-Dex for polymorphisms of killer-cell immunoglobulin-like receptors (KIR), human leukocyte antigen (HLA) class I, and FCGR3A loci. In vitro ADCC assay, coincubating primary NK cells expressing specific KIR repertoire with multiple myeloma cell lines (MM cells) expressing selected HLA class I ligands, was used to confirm the identified genetic correlatives of clinical response.

Results

Patients with KIR3DL2+ and its cognate-ligand HLA-A3/11+ had superior PFS than patients missing this combination (HR=0.43; p=0.02), while patients carrying KIR2DL1+ and HLA-C2C2+ compared with to patients missing this pair showed short PFS (HR=3.54; p=0.05). Patients with KIR3DL2+ and HLA-A3/11+ plus high-affinity FCGR3A-158V allele showed the most prolonged PFS (HR=0.35; p=0.007). Consistent with these clinical data, mechanistic experiments demonstrated that NK cells expressing KIR3DL2 trigger greater ADCC when MM cells express HLA-A3/11. Inversely, NK cells expressing KIR2DL1 do not kill if MM cells express the HLA-C2C2 ligand. NK cells expressing high-affinity FCGR3A-158VV-induced greater ADCC compared with those with low-affinity FCGR3A-158FF.

Conclusions

Our results suggest that KIR3DL2+ and HLA-A3/11+ with FCGR3A-158V markers lead to enhanced Isa-dependent NK-mediated cytolysis against MM cells and results in improved PFS in patients with RRMM treated by Isa-Len-Dex. Moreover, the presence of KIR2DL1+ and HLA-C2C2+ identifies patients who may have a lower response to Isa-Len-Dex therapy linked to a reduced NK-mediated ADCC. These biomarkers could potentially identify, via precision medicine, patients more likely to respond to Isa-Len-Dex immunotherapy.

Trial registration number

NCT01749969.
#3083 Fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): an interoceptive predictive coding model of pain and fatigue expression
Authors: Sharp Harriet , Themelis Kristy , Amato Marisa , Barritt Andrew , Davies Kevin , Harrison Neil , Garfinkel Sarah , Critchley Hugo , Eccles Jessica
Published: July 2021

Introduction

The aetiology and pathophysiology of fibromyalgia and ME/CFS are poorly characterised but altered inflammatory, autonomic and interoceptive processes have been implicated. Interoception has been conceptualised as a predictive coding process; where top-down prediction signals compare to bottom-up afferents, resulting in prediction error signals indicating mismatch between expected and actual bodily states. Chronic dyshomeostasis and elevated interoceptive prediction error signals have been theorised to contribute to the expression of pain and fatigue in fibromyalgia and ME/CFS.

Objectives/Aims

To investigate how altered interoception and prediction error relates to baseline expression of pain and fatigue in fibromyalgia and ME/CFS and in response to an inflammatory challenge.

Methods

Sixty-five patients with fibromyalgia and/or ME/CFS diagnosis and 26 matched controls underwent baseline assessment: self-report questionnaires assessing subjective pain and fatigue and objective measurements of pressure-pain thresholds. Participants received injections of typhoid (inflammatory challenge) or saline (placebo) in a randomised, double-blind, crossover design, then completed heartbeat tracking task (assessing interoceptive accuracy). Porges Body Questionnaire assessed interoceptive sensibility. Interoceptive prediction error (IPE) was calculated as discrepancy between objective accuracy and subjective sensibility.

Results

Patients with fibromyalgia and ME/CFS had significantly higher IPE (suggesting tendency to over-estimate interoceptive ability) and interoceptive sensibility, despite no differences in interoceptive accuracy. IPE and sensibility correlated positively with all self-report fatigue and pain measures, and negatively with pain thresholds. Following inflammatory challenge, IPE correlated negatively with the mismatch between subjective and objective measures of pain induced by inflammation.

Conclusions

This is the first study to reveal altered interoception processes in patients with fibromyalgia and ME/CFS, who are known to have dysregulated autonomic function. Notably, we found elevated IPE in patients, correlating with their subjective experiences of pain and fatigue. We hypothesise a predictive coding model, where mismatch between expected and actual internal bodily states (linked to autonomic dysregulation) results in prediction error signalling which could be metacognitively interpreted as chronic pain and fatigue. Our results demonstrate potential for further exploration of interoceptive processing in patients with fibromyalgia and ME/CFS, aiding understanding of these poorly defined conditions and providing potential new targets for diagnostic and therapeutic intervention.
Thrombectomy for secondary distal, medium vessel occlusions of the posterior circulation: seeking complete reperfusion
Authors: Meyer Lukas , Stracke Christian Paul , Wallocha Marta , Broocks Gabriel , Sporns Peter B , Piechowiak Eike I , Kaesmacher Johannes , Maegerlein Christian , Dorn Franziska , Zimmermann Hanna , Naziri Weis , Abdullayev Nuran , Kabbasch Christoph , Behme Daniel , Jamous Ala , Maus Volker , Fischer Sebastian , Möhlenbruch Markus , Weyland Charlotte Sabine , Langner Soenke , Meila Dan , Miszczuk Milena , Siebert Eberhard , Lowens Stephan , Krause Lars Udo , Yeo Leonard LL , Tan Benjamin YQ , Gopinathan Anil , Gory Benjamin , Arenillas Juan F , Navia Pedro , Raz Eytan , Shapiro Maksim , Arnberg Fabian , Zeleňák Kamil , Martínez-Galdámez Mario , Kastrup Andreas , Papanagiotou Panagiotis , Kemmling Andre , Psychogios Marios N , Andersson Tommy , Chapot René , Fiehler Jens , Hanning Uta
Published: July 2021

Background

Whether to approach distal occlusions endovascularly or not in medium-sized vessels secondary to proximal large vessel occlusion stroke remains unanswered.

Objective

To investigates the technical feasibility and safety of thrombectomy for secondary posterior circulation distal, medium vessel occlusions (DMVO).

Methods

TOPMOST (Treatment fOr Primary Medium vessel Occlusion STroke) is an international, retrospective, multicenter, observational registry of patients treated for distal cerebral artery occlusions. This study subanalysis endovascularly treated occlusions of the posterior cerebral artery in the P2 and P3 segment secondary preprocedural or periprocedural thrombus migration between January 2014 and June 2020. Technical feasibility was evaluated with the modified Thrombolysis in Cerebral Infarction (mTICI) scale. Procedural safety was assessed by the occurrence of symptomatic intracranial hemorrhage (sICH) and intervention-related serious adverse events.

Results

Among 71 patients with secondary posterior circulation DMVO who met the inclusion criteria, occlusions were present in 80.3% (57/71) located in the P2 segment and in 19.7% (14/71) in the P3 segment. Periprocedural migration occurred in 54.9% (39/71) and preprocedural migration in 45.1% (32/71) of cases. The first reperfusion attempt led in 38% (27/71) of all cases to mTICI 3. On multivariable logistic regression analysis, increased numbers of reperfusion attempts (adjusted odds ratio (aOR)=0.39, 95% CI 0.29 to 0.88, p=0.009) and preprocedural migration (aOR=4.70, 95% CI,1.35 to 16.35, p=0.015) were significantly associated with mTICI 3. sICH occurred in 2.8% (2/71).

Conclusion

Thrombectomy for secondary posterior circulation DMVO seems to be safe and technically feasible. Even though thrombi that have migrated preprocedurally may be easier to retract, successful reperfusion can be achieved in the majority of patients with secondary DMVO of the P2 and P3 segment.
Effect of quitting smoking on health outcomes during treatment for tuberculosis: secondary analysis of the TB & Tobacco Trial
Authors: Siddiqi Kamran , Keding Ada , Marshall Anna-Marie , Dogar Omara , Li Jinshuo , Huque Rumana , Fatima Razia , Khan Amina , Elsey Helen , Gabe Rhian , Kotz Daniel , Sheikh Aziz
Published: July 2021

Background

Despite treatment, patients with tuberculosis (TB) who smoke have poorer outcomes compared with non-smokers. It is unknown, however, if quitting smoking during the 6 months of TB treatment improves TB outcomes.

Methods

The TB & Tobacco Trial was a double-blind, placebo-controlled randomised trial of cytisine for smoking cessation in 2472 patients with pulmonary TB in Bangladesh and Pakistan. In a secondary analysis, we investigated the hypothesis that smoking cessation improves health outcomes in patients during the TB treatment course. The outcomes included an eight-point TB clinical score, sputum conversion rates, chest X-ray grades, quality of life (EQ-5D-5L), TB cure plus treatment completion rates and relapse rates. These were compared between those who stopped smoking and those who did not, using regression analysis.

Results

We analysed the data of 2273 (92%) trial participants. Overall, 25% (577/2273) of participants stopped smoking. Compared with non-quitters, those who quit had better TB cure plus treatment completion rates (91% vs 80%, p<0.001) and lower TB relapse rates (6% vs 14%, p<0.001). Among quitters, a higher sputum conversion rate at week 9 (91% vs 87%, p=0.036), lower mean TB clinical scores (−0.20 points, 95% CI −0.31 to −0.08, p=0.001) and slightly better quality of life (mean EQ-5D-5L 0.86 vs 0.85, p=0.015) at 6 months were also observed. These differences, except quality of life, remained statistically significant after adjusting for baseline values, trial arm and TB treatment adherence rates.

Conclusion

Patients with TB who stop smoking may have better outcomes than those who don’t. Health professionals should support patients in stopping smoking.
Does pay-for-performance improve patient outcomes in acute exacerbation of COPD admissions?
Authors: Stone Philip W , Adamson Alexander , Hurst John R , Roberts C Michael , Quint Jennifer K
Published: July 2021

Background

The COPD Best Practice Tariff (BPT) is a pay-for-performance scheme in England that incentivises review by a respiratory specialist within 24 hours of admission and completion of a list of key care components prior to discharge, known as a discharge bundle, for patients admitted with acute exacerbation of COPD (AECOPD). We investigated whether the two components of the COPD BPT were associated with lower 30-day mortality and readmission in people discharged following AECOPD.

Methods

Longitudinal study of national audit data containing details of AECOPD admissions in England and Wales between 01 February 2017 and 13 September 2017. Data were linked with national admissions and mortality data. Mixed-effects logistic regression, using a random intercept for hospital to adjust for clustering of patients, was used to determine the relationship between the COPD BPT criteria (combined and separately) and 30-day mortality and readmission. Models were adjusted for age, sex, socioeconomic status, length of stay, smoking status, Charlson comorbidity index, mental illness and requirement for oxygen or noninvasive ventilation during admission.

Results

28 345 patients discharged from hospital following AECOPD were included. 37% of admissions conformed to the two COPD BPT criteria. No relationship was observed between BPT conforming admissions and 30-day mortality (OR: 1.09 (95% CI 0.92 to 1.29)) or readmissions (OR: 0.96 (95% CI 0.90 to 1.02)). No relationship was observed between either of the individual COPD BPT components and 30-day mortality or readmissions. However, a specialist review at any time during admission was associated with lower inpatient mortality (OR: 0.69 (95% CI 0.58 to 0.81)).

Conclusion

Completion of the combined COPD BPT criteria does not appear associated with a reduction in 30-day mortality or readmission. However, specialist review was associated with reduced inpatient mortality. While it is difficult to argue that discharge bundles do not improve care, this analysis questions whether the pay-for-performance model improves mortality or readmissions.
Impact of standardised packaging in the UK on warning salience, appeal, harm perceptions and cessation-related behaviours: a longitudinal online survey
Authors: Moodie Crawford , Best Catherine , Hitchman Sara C , Critchlow Nathan , MacKintosh Anne-Marie , McNeill Ann , Stead Martine
Published: July 2021

Introduction

In the UK, since 20 May 2017, tobacco companies must sell cigarettes and rolling tobacco in standardised packs.

Methods

Three waves of a longitudinal online survey with smokers (≥16) before standardised packaging (wave 1 (W1): April to May 2016) and after standardised packaging (wave 2 (W2): September to November 2017; wave 3 (W3): May to July 2019). Of the 6233 smokers at W1, 4293 responded at W2 and 3175 at W3. We explored smokers’ response to warning salience, appeal (appeal, quality, value, satisfaction and taste compared with a year ago), harm (harmfulness compared with a year ago, harm compared with other brands and whether some brands have more harmful substances), and quit plans, attempts and quitting.

Results

Compared with W1, the proportions noticing warnings first on packs, and rating cigarettes/rolling tobacco less appealing and worse value than a year ago, were higher at W2 and W3. Disagreeing that some brands contain more harmful substances was higher at W2. Interactions between social grade and survey wave for warning salience, and each appeal and harm outcome, were non-significant. Smokers switching from not noticing warnings first at W1 to noticing warnings first at W2, or who had a lower composite appeal score at W2, were more likely to plan to quit and to have made a quit attempt at W2. Smokers who switched to disagreeing that some brands contain more harmful substances at W2, after giving a different response at W1, were more likely to quit at W3.

Conclusions

Standardised packaging appears to be having the intended impacts.
Solitons to the derivative nonlinear Schrödinger equation: Double Wronskians and reductions
Authors: Liu Shu-Zhi , Wu Hua
Published: July 2021

In this paper, we derive solutions to the derivative nonlinear Schrödinger equation, which are associated to real and complex discrete eigenvalues of the Kaup–Newell spectral problem. These solutions are obtained by investigating double Wronskian solutions of the coupled Kaup–Newell equations and their reductions by means of bilinear method and a reduction technique. The reduced equations include the derivative nonlinear Schrödinger equation and its nonlocal version. Some obtained solutions allow not only periodic behavior, but also solitons on periodic background. Dynamics are illustrated.
Equilibrium analysis of an immersed rigid leaflet by the virtual element method
Authors: Beirão da Veiga L. , Canuto C. , Nochetto R. H. , Vacca G.
Published: July 2021

We study, both theoretically and numerically, the equilibrium of a hinged rigid leaflet with an attached rotational spring, immersed in a stationary incompressible fluid within a rigid channel. Through a careful investigation of the properties of the domain functional describing the angular momentum exerted by the fluid on the leaflet (which depends on both the leaflet angular position and its thickness), we identify sufficient conditions on the spring stiffness function for the existence (and uniqueness) of equilibrium positions. This study resorts to techniques from shape differential calculus. We propose a numerical technique that exploits the mesh flexibility of the Virtual Element Method (VEM). A (polygonal) computational mesh is generated by cutting a fixed background grid with the leaflet geometry, and the problem is then solved with stable VEM Stokes elements of degrees [Formula: see text] and [Formula: see text] combined with a bisection algorithm. We prove quasi-optimal error estimates and present a large array of numerical experiments to document the accuracy and robustness with respect to degenerate geometry of the proposed methodology.
DYNAMIC BIOREACTOR MODEL TO MIMIC EARLY CARDIAC FIBROSIS IN DIABETES
Authors: MARSH SPENCER , RAUDAT MADELINE , LEFEBER BETHANY , HERNDON LAURA BETH , HERBERT HOWARD , MCCALLUM LAURA , SIMIONESCU AGNETA
Published: July 2021

In clinical diabetic cardiomyopathy, hyperglycemia and dyslipidemia induce tissue injury, activation of cardiac fibroblasts and interstitial and perivascular fibrosis. Myofibroblasts repair the injured tissue by increasing collagen deposition in the cardiac interstitium and suppressing the activity of matrix metalloproteinases. The goal of this study was to find an ideal model to mimic the effect of high glucose concentration on human cardiac fibroblast activation. The profibrotic role of the transforming growth factor-[Formula: see text] (TGF-[Formula: see text]) and the protective modulation of nitric oxide were examined in two-dimensional and three-dimensional cell culture models, as well as tissue engineering models, that involved the use of cardiac fibroblasts cultured within myocardial matrix scaffolds mounted in a bioreactor that delivered biochemical and mechanical stimuli. Results showed that high glucose levels were potent pro-fibrotic stimuli. In addition, high glucose levels in concert with TGF-[Formula: see text] constituted very strong signals that induced human cardiac fibroblast activation. Cardiac fibroblasts cultured within decellularized myocardial scaffolds and exposed to biochemical and mechanical stimuli represented an adequate model for this pathology. In conclusion, the bioreactor platform was instrumental in establishing an in vitro model of early fibrosis; this platform could be used to test the effects of various agents targeted to mitigate the fibrotic processes.