bluuebunny/crossref_metadata_2025 huggingface dataset:
Bilateral internal thoracic artery coronary grafting: risks and benefits in elderly patients
Authors: Zhou Zhuoming , Fu Guangguo , Huang Suiqing , Chen Sida , Liang Mengya , Wu Zhongkai
Published: December 2021

Aims

Whether bilateral internal thoracic artery (BITA) grafting benefits elderly patients in coronary artery bypass grafting (CABG) remains unclear since they tend to have a limited life expectancy and severe comorbidities. We aim to evaluate the outcomes of BITA vs. single internal thoracic artery (SITA) grafting in elderly patients.

Methods and results

A meta-analysis was performed by database searching until May 2021. Studies comparing BITA and SITA grafting among elderly patients were included. One randomized controlled trial, nine propensity score matching, and six unmatched studies were identified, with a total of 18 146 patients (7422 received BITA grafting and 10 724 received SITA grafting). Compared with SITA grafting, BITA grafting had a higher risk of deep sternal wound infection (DSWI) [odds ratio: 1.67; 95% confidence interval (CI): 1.22–2.28], and this risk could not be significantly reduced by the skeletonization technique. Meanwhile, BITA grafting was associated with a higher long-term survival [hazard ratio: 0.83; 95% CI: 0.77–0.90], except for the octogenarian subgroup. Reconstructed Kaplan–Meier survival curves revealed 4-year, 8-year, and 12-year overall survival rates of 85.5%, 66.7%, and 45.3%, respectively, in the BITA group and 79.3%, 58.6%, and 34.9%, respectively, in the SITA group. No significant difference was observed in early mortality, perioperative myocardial infarction, perioperative cerebral vascular accidents, or re-exploration for bleeding.

Conclusion

Compared with SITA grafting, BITA grafting could provide a long-term survival benefit for elderly patients, although this benefit remained uncertain in octogenarians. Meanwhile, elderly patients who received BITA were associated with a higher risk of DSWI and such a risk could not be eliminated by the skeletonization technique.
The Forgotten Liberal Social Reform? Marriage with a Deceased Wife’s Sister, Political Nonconformity and the New Liberalism in Edwardian Britain
Authors: Barrie David G
Published: December 2021

This article examines why Victorian Britain’s longest-running political controversy—the sixty-four-year campaign to legalise marriage between a widower and his deceased wife’s sister—was finally resolved in 1907. It explores why the Liberal government decided to support reform, what strategies it adopted and how it was able to force a deceased wife’s sister bill through an intransigent House of Lords that had, for more than half a century, succeeded in blocking similar bills. The article recognises that a multitude of factors—social, theological, imperial and legal—shaped opinion on the issue. Nonetheless, it argues that the Liberal government’s backing for marriage with a deceased wife’s sister (MDWS) should be viewed, in terms of its hegemonic public presentation, as the forgotten Liberal social reform. In keeping with the emerging New Liberalism, MDWS was packaged primarily as a social relief measure that spoke to the Liberal Party’s growing interest in the poor, child welfare, social justice, women’s rights and state support for workers. The commitment to easing the plight of those affected by the existing prohibition was real, but behind the public rhetoric lay a desire to stem nonconformist discontent among the Liberal Party’s electoral base, and an evolving constitutional crisis between the houses of parliament which gave the issue greater symbolic significance. For many peers, reform had become more than just palatable or desirable. It was necessary in the light of a change in colonial marriage law that had sought to address colonial grievances, promote imperial unity and better safeguard inherited wealth and social status.
Subduction earthquake sequences in a non-linear visco-elasto-plastic megathrust
Authors: Dal Zilio Luca , Lapusta Nadia , Avouac Jean-Philippe , Gerya Taras
Published: December 2021

We present a 2-D thermomechanical computational framework for simulating earthquake sequences in a non-linear visco-elasto-plastic compressible medium. The method is developed for a plane-strain problem and incorporates an invariant formulation of the classical rate- and state-dependent friction law and an adaptive time-stepping, which allows the time step to vary by many orders of magnitude during a simulation. Long-term tectonic convergence is imposed by displacing a boundary at a constant rate, whereas temperature-dependent viscosity is solved using a rapidly converging Newton–Raphson scheme. The 2-D volume is discretized using finite differences on a fully staggered grid and marker-in-cell techniques. An adaptive free-surface approximation is used to modulate the air viscosity with the time step, which allows stresses to vanish on the free surface during the propagation of fast slipping events. We present a set of increasingly complex models in which we investigate how inertia, radiation damping, thermally activated non-linear rheology and off-megathrust splay-fault events affect sequences of seismic and aseismic slip on a simplified subduction megathrust. The new method provides a unique computational framework to analyse earthquake sequences and to connect forearc deformation with the dynamic properties of the megathrust, thus providing a physical link between observations spanning from slow interseismic strain accumulation to localized coseismic slip of individual earthquakes and post-seismic viscoelastic relaxation.
Dose- and LET-dependent changes in mouse skin contracture up to a year after either single dose or fractionated doses of carbon ion or gamma rays
Authors: Ando Koichi , Yoshida Yukari , Hirayama Ryoichi , Koike Sachiko , Matsufuji Naruhiro
Published: December 2021

Time dependence of relative biological effectiveness (RBE) of carbon ions for skin damage was investigated to answer the question of whether the flat distribution of biological doses within a Spread-Out Bragg peak (SOBP) which is designed based on in vitro cell kill could also be flat for in vivo late responding tissue. Two spots of Indian ink intracutaneously injected into the legs of C3H mice were measured by calipers. An equieffective dose to produce 30% skin contraction was calculated from a dose–response curve and used to calculate the RBE of carbon ion beams. We discovered skin contraction progressed after irradiation and then reached a stable/slow progression phase. Equieffective doses decreased with time and the decrease was most prominent for gamma rays and least prominent for 100 keV/μm carbon ions. Survival parameter of alpha but not beta in the linear-quadratic model is closely related to the RBE of carbon ions. Biological doses within the SOBP increased with time but their distribution was still flat up to 1 year after irradiation. The outcomes of skin contraction studies suggest that (i) despite the higher RBE for skin contracture after carbon ions compared to gamma rays, gamma rays can result in a more severe late effect of skin contracture. This is due to the carbon effect saturating at a lower dose than gamma rays, and (ii) the biological dose distribution throughout the SOBP remains approximately the same even one year after exposure.
Bayesian Inference for Estimating Subset Proportions using Differentially Private Counts
Authors: Li Linlin , Reiter Jerome P
Published: December 2021

Recently, several organizations have considered using differentially private algorithms for disclosure limitation when releasing count data. The typical approach is to add random noise to the counts sampled from, for example, a Laplace distribution or symmetric geometric distribution. One advantage of this approach, at least for some differentially private algorithms, is that analysts know the noise distribution and hence have the opportunity to account for it when making inferences about the true counts. In this article, we present Bayesian inference procedures to estimate the posterior distribution of a subset proportion, that is, a ratio of two counts, given the released values. We illustrate the methods under several scenarios, including when the released counts come from surveys or censuses. Using simulations, we show that the Bayesian procedures can result in accurate inferences with close to nominal coverage rates.
The role ofAUX1during lateral root development in the domestication of the model C4 grassSetaria italica
Authors: Tang Sha , Shahriari Mojgan , Xiang Jishan , Pasternak Taras , Igolkina Anna , Aminizade Somayeh , Zhi Hui , Gao Yuanzhu , Roodbarkelari Farshad , Sui Yi , Jia Guanqing , Wu Chuanyin , Zhang Linlin , Zhao Lirong , Li Xugang , Meshcheryakov Georgy , Samsonova Maria , Diao Xianmin , Palme Klaus , Teale William
Published: December 2021

C4 photosynthesis increases the efficiency of carbon fixation by spatially separating high concentrations of molecular oxygen from Rubisco. The specialized leaf anatomy required for this separation evolved independently many times. The morphology of C4 root systems is also distinctive and adapted to support high rates of photosynthesis; however, little is known about the molecular mechanisms that have driven the evolution of C4 root system architecture. Using a mutant screen in the C4 model plant Setaria italica, we identify Siaux1-1 and Siaux1-2 as root system architecture mutants. Unlike in S. viridis, AUX1 promotes lateral root development in S. italica. A cell by cell analysis of the Siaux1-1 root apical meristem revealed changes in the distribution of cell volumes in all cell layers and a dependence of the frequency of protophloem and protoxylem strands on SiAUX1. We explore the molecular basis of the role of SiAUX1 in seedling development using an RNAseq analysis of wild-type and Siaux1-1 plants and present novel targets for SiAUX1-dependent gene regulation. Using a selection sweep and haplotype analysis of SiAUX1, we show that Hap-2412TT in the promoter region of SiAUX1 is an allele which is associated with lateral root number and has been strongly selected for during Setaria domestication.
Acquired Factor VIII Inhibitors: A Case Study
Authors: Walradth Eric A
Published: December 2021

The physiology of hemostasis is one of high complexity that involves the initiation, amplification, and propagation of the many moving parts of the hemostatic system and its regulatory mechanisms. It is imperative that clinical laboratory professionals have a strong understanding of the many intricacies of the physiology of coagulation and its in vitro testing. An elongated activated partial thromboplastin time can have several causes, and the correct cause must be elucidated in a timely manner for proper treatment. A mixing study with normal pooled plasma should be performed to evaluate for the presence of an inhibitor vs factor deficiency. Factor inhibitors, specifically factor VIII in this case study, should be titered so that the clinician can decide which treatment may work best for the patient. Continued monitoring of factor levels and inhibitor titers should be conducted to follow the resolution or progression of inhibitor presence.
The Air Force Visiting Surgeon Program: Development, Outcomes, and Future Application
Authors: Fox Justin P , Latham Kerry P
Published: December 2021

Introduction

Active duty service members and their families have limited access to subspecialty surgical care when assigned OCONUS. To address this issue, the Air Force Visiting Surgeon Program (VSP) was created to push subspecialty care to these locations. Visiting Surgeon Program was accomplished using temporary duty (TDY) orders. We conducted this 12-year review, 2009-2021, of the program to assess objective measures of impact, identify key lessons learned, and consider the program’s future.

Materials and Methods

In 2009, the senior author, Col Latham, performed a cost analysis of plastic surgery care provided at OCONUS installations and found that TRICARE Overseas often paid rates substantially higher than a TDY assignment for a single procedure. To improve beneficiaries’ access to care while providing a cost savings to the health care system, 2-week plastic surgery missions were proposed to interested OCONUS military treatment facilities (MTFs). Ultimately, four sites selected to host the program in Alaska, Italy, England, and Japan. These sites were selected based on patient volumes, operating room capacity, and local command and surgeon support. By 2015, the Air Force formalized the program via Air Force Instruction 44-102 which outlined roles and responsibilities of MTF Commanders; established points of contact; and instituted key safety measures.

Results

To date, 58 missions have been completed by 21 surgeons through the VSP at Aviano Air Base (Italy; 24.1%), Joint Base Elmendorf-Richardson (Alaska; 31.0%), Royal Air Force Lakenheath (England; 27.6%), and Yokota Air Base (Japan; 17.2%). While primarily an Air Force program, 17% (10/58) of missions were supported Army or Navy surgeons. Overall, 2,000 patient consultations and 865 surgical cases were performed avoiding $6.7 million in cost. In addition to direct beneficiary care, the VSP also contributed to the participating surgeon and host surgical teams mission readiness.

Conclusions

The VSP provides a template to make select subspecialty surgical care available in a cost-effective manner across the military health system, while also providing a model for the forward deployment of military plastic surgeons and triservice collaboration.
Supernovae in colliding-wind binaries: observational signatures in the first year
Authors: Pejcha Ondřej , Calderón Diego , Kurfürst Petr
Published: December 2021

When a core-collapse supernova (SN) explodes in a binary star system, the ejecta might encounter an overdense shell, where the stellar winds of the two stars previously collided. In this work, we investigate effects of such interactions on SN light curves on time-scales from the early flash ionization signatures to approximately one year after the explosion. We construct a model of the colliding-wind shell in an orbiting binary star system and we provide an analytical expression for the shell thickness and density, which we calibrate with three-dimensional adaptive mesh refinement hydrodynamical simulations probing different ratios of wind momenta and different regimes of radiative cooling efficiency. We model the angle-dependent interaction of SN ejecta with the circumstellar medium and estimate the shock radiative efficiency with a realistic cooling function. We find that the radiated shock power exceeds typical Type IIP SN luminosity only for double red supergiant binaries with mass ratios q ≳ 0.9, wind mass-loss rates $\dot{M}\gtrsim 10^{-4}\, \rm M_\odot \, \text{yr}^{-1}$, and separations between about 50 and 1500 au. The required $\dot{M}$ increases for binaries with smaller q or primaries with faster wind. We estimate that ≪1 per cent of all collapsing massive stars satisfy the conditions on binary mass ratio and separation. Recombination luminosities due to colliding wind shells are at most a factor of 10 higher than for an otherwise unperturbed constant-velocity wind, but higher densities associated with wind acceleration close to the star provide much stronger signal.
The discovery of rest-frame UV colour gradients and a diversity of dust morphologies in bright z ≃ 7 Lyman-break galaxies
Authors: Bowler R A A , Cullen F , McLure R J , Dunlop J S , Avison A
Published: December 2021

We present deep ALMA dust continuum observations for a sample of luminous (MUV < −22) star-forming galaxies at z ≃ 7. We detect five of the six sources in the far-infrared (FIR), providing key constraints on the obscured star formation rate (SFR) and the infrared-excess-β (IRX–β) relation without the need for stacking. Despite the galaxies showing blue rest-frame ultraviolet (UV) slopes (β ≃ −2) we find that 35–75 per cent of the total SFR is obscured. We find the IRX–β relation derived for these z ≃ 7 sources is consistent with that found for local starburst galaxies. Using our relatively high-resolution (FWHM $\simeq 0.7\, {\rm arcsec}$) observations we identify a diversity of dust morphologies in the sample. We find both compact emission that appears offset relative to the unobscured components and extended dust emission that is co-spatial with the rest-frame UV light. In the majority of the sources, we detect strong rest-frame UV colour gradients (with up to Δβ ≃ 0.7–1.4) as probed by the multiband UltraVISTA ground-based data. The observed redder colours are spatially correlated with the location of the FIR detection. Our results show that even in bright Lyman-break galaxies at z ≃ 7 the peak of the star formation is typically hosted by the fainter, redder, regions in the rest-frame UV, which have an obscured fraction of fobs ≥ 0.8. As well as demonstrating the importance of dust obscured star formation within the Epoch of Reionization, these observations provide an exciting taster of the rich spatially resolved data sets that will be obtained from JWST and high-resolution ALMA follow-up at these redshifts.
Constraining spinning primordial black holes with global 21-cm signal
Authors: Natwariya Pravin Kumar , Nayak Alekha C , Srivastava Tripurari
Published: December 2021

We study the upper projected bounds on the dark matter fraction in the form of the primordial black holes (PBHs) with a non-zero spin by using the absorption feature in the global 21-cm signal at redshift z ≈ 17. The mass and spin are fundamental properties of a black hole, and they can substantially affect the evaporation rate of the black hole. The evaporating black hole can inject energy into the intergalactic medium and heat the gas. Subsequently, it can modify the absorption amplitude in the global 21-cm signal. Therefore, the absorption feature in the 21-cm signal can provide a robust bound on PBHs. We analyse the projected constraints on the dark matter fraction in the form of both spinning and non-spinning PBHs. The constraints are more stringent for spinning PBHs than non-spinning ones. We also compare these bounds with other observations and find the most stringent lower constraint on PBHs mass, which is allowed to constitute the entire dark matter to 6.7 × 1017 g for extremal spinning PBHs.
DNA repair and response to sperm DNA damage in oocytes and embryos, and the potential consequences in ART: a systematic review
Authors: Newman H , Catt S , Vining B , Vollenhoven B , Horta F
Published: December 2021

Sperm DNA damage is considered a predictive factor for the clinical outcomes of patients undergoing ART. Laboratory evidence suggests that zygotes and developing embryos have adopted specific response and repair mechanisms to repair DNA damage of paternal origin. We have conducted a systematic review in accordance with guidelines from Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) to identify and review the maternal mechanisms used to respond and repair sperm DNA damage during early embryonic development, how these mechanisms operate and their potential clinical implications. The literature search was conducted in Ovid MEDLINE and Embase databases until May 2021. Out of 6297 articles initially identified, 36 studies were found to be relevant through cross referencing and were fully extracted. The collective evidence in human and animal models indicate that the early embryo has the capacity to repair DNA damage within sperm by activating maternally driven mechanisms throughout embryonic development. However, this capacity is limited and likely declines with age. The link between age and decreased DNA repair capacity could explain decreased oocyte quality in older women, poor reproductive outcomes in idiopathic cases and patients who present high sperm DNA damage. Ultimately, further understanding mechanisms underlying the maternal repair of sperm DNA damage could lead to the development of targeted therapies to decrease sperm DNA damage, improved oocyte quality to combat incoming DNA insults or lead to development of methodologies to identify individual spermatozoa without DNA damage.
Modeling of 3D trajectory of Hayabusa2 re-entry based on acoustic observations
Authors: Nishikawa Yasuhiro , Yamamoto Masa-yuki , Sansom Eleanor K , Devillepoix Hadrien A R , Towner Martin C , Hiramatsu Yoshihiro , Kawamura Taichi , Fujita Kazuhisa , Yoshikawa Makoto , Ishihara Yoshiaki , Hamama Islam , Segawa Norihisa , Kakinami Yoshihiro , Katao Hiroshi , Inoue Yuichiro , Bland Philip A
Published: December 2021

On 2020 December 5 at 17:28 UTC, Japan Aerospace Exploration Agency’s Hayabusa2 sample return capsule (SRC) re-entered Earth’s atmosphere. The capsule passed through the atmosphere at supersonic speeds, emitting sound and light. The inaudible sound was recorded by infrasound sensors installed by Kochi University of Technology and Curtin University. Based on analysis of the recorded infrasound, the trajectory of the SRC in two cases, one with constant-velocity linear motion and the other with silent flight, could be estimated with an accuracy of ${0{_{.}^{\circ}}5}$ in elevation and 1° in direction. A comparison with optical observations suggests a state of flight in which no light is emitted but sound is emitted. In this paper, we describe the method and results of the trajectory estimation.
Counseling Veterans with Chronic Pain During the COVID-19 Pandemic: A Secondary Analysis of a Randomized Controlled Trial
Authors: Lazar Christina M , Rosen Marc I , Sellinger John , Mattocks Kristin , Navarra Lisa , Ross Kimberly A , Martino Steve
Published: December 2021

Introduction

Veterans with chronic pain could be vulnerable during the COVID-19 pandemic. We qualitatively explored the impact of the COVID-19 pandemic on a sample of veterans receiving brief counseling focused on pain management in an ongoing clinical trial and discuss how the pandemic affected the process of motivating veterans with chronic pain to engage in interdisciplinary multimodal pain treatment at the Department of Veteran Affairs.

Methods

Segments of audio-recorded counseling sessions containing content about the pandemic were transcribed and coded to identify key concepts emerging from individual counselor–participant transactions. Themes that emerged were examined with constant comparison analysis.

Results

Three major themes emerged. 1) The pandemic caused a disruption in pain management service delivery, resulting in changes to the way veterans receive services or manage their pain symptoms. 2) The pandemic offered opportunities for resilience and personal growth as veterans with chronic pain reflected on their lives and personal goals. 3) The pandemic brought veterans’ mental health issues to the forefront, and these should be addressed as part of a comprehensive pain management approach.

Discussion

Discussion of the COVID-19 pandemic during pain treatment counseling sessions highlighted negative and positive ways participants were affected by the pandemic. These discussions provided counselors with a unique opportunity to facilitate behavior change by focusing on characteristics of resilience to motivate individuals with chronic pain to adapt and adopt positive behaviors and outlooks to improve their pain experience and quality of life.

Conclusions

Counselors can leverage feelings of resilience and personal growth to motivate veterans’ use of adaptive coping skills and a wider array of pain management services.
Finite Element Comparison of the Spring Distraction System and the Traditional Growing Rod for the Treatment of Early Onset Scoliosis
Authors: Lemans Justin V.C. , Kodigudla Manoj K. , Kelkar Amey V. , Jayaswal Daksh , Castelein René M. , Kruyt Moyo C. , Goel Vijay K. , Agarwal Aakash
Published: December 2021

Study Design.

Finite element analysis (FEA).

Objective.

The aim of this study was to determine biomechanical differences between traditional growing rod (TGR) and spring distraction system (SDS) treatment of early-onset scoliosis.

Summary of Background Data.

Many “growth-friendly” implants like the TGR show high rates of implant failure, spinal stiffening, and intervertebral disc (IVD) height loss. We developed the SDS, which employs continuous, dynamic forces to mitigate these limitations. The present FEA compares TGR and SDS implantation, followed by an 18-month growth period.

Methods.

Two representative, ligamentous, scoliotic FEA models were created for this study; one representing TGR and one representing SDS. initial implantation, and up to 18 months of physeal spinal growth were simulated. The SDS model was continuously distracted over this period; the TGR model included two additional distractions following index surgery. Outcomes included differences in rod stress, spinal morphology and iVD stress-shielding.

Results.

Maximum postoperative von Mises stress was 249MPa for SDS, and 205MPa for TGR. During the 6-month TGR distraction, TGR rod stress increased over two-fold to a maximum stress of 417MPa, compared to a maximum of 262 MPa in the SDS model at 6-month follow-up. During subsequent follow-up periods, TGR rod stress remained consistently higher than stresses in the SDS model. Additional lengthenings in the TGR model led to a smaller residual curve (16.08) and higher T1-S1 growth (359 mm) at 18-month follow-up compared to the SDS model (26.98, 348 mm). During follow-up, there was less stress-shielding of the IVDs in the SDS model, compared to the TGR model. At 18-month follow-up, upper and lower IVD surfaces of the SDS model were loaded more in compression than their TGR counterparts (mean upper: +112 ± 19N; mean lower: +100 ± 17N).

Conclusion.

In the present FEA, TGR treatment resulted in slightly larger curve correction compared to SDS, at the expense of increased IVD stress-shielding and a higher risk of rod fractures.

Level of Evidence.

N/A
lncRNA Nuclear Factor of Activated T Cells Knockdown Alleviates Hypoxia/Reoxygenation-induced Cardiomyocyte Apoptosis by Upregulating HIF-1α Expression
Authors: Deng Xiaofeng , Liu Yongqing , Xu Zesheng , Wang Zichao
Published: December 2021

Acute myocardial infarction (AMI) has become the most common cause of death in the developed countries. However, its pathogenesis is poorly understood. Increasing studies have revealed that lncRNAs are important modulators of AMI development. This study aimed to explore the function of lncRNA noncoding repressor of nuclear factor of activated T cells (NRON) in hypoxia/reoxygenation (H/R)-stimulated H9c2 cells. NRON expression in peripheral blood of AMI patients and H/R-stimulated H9c2 cells was measured by quantitative real-time polymerase chain reaction. H9c2 cells were transfected with si-NRON or cotransfected with si-NRON and si-hypoxia-inducible factor-1 alpha (HIF-1α). The viability and apoptosis of these cells were evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assay and flow cytometer, respectively. In addition, HIF-1α, AKT/mTOR signal pathways and ERK1/2 were detected by western blot. NRON knockdown in the myocardial infarction mouse model was conducted through adeno-associated virus injection, and cardiac function was evaluated by motion-mode echocardiography. The results showed that NRON was highly expressed in peripheral blood of AMI patients and H/R-stimulated H9c2 cells. NRON knockdown promoted cell viability and inhibited cell apoptosis of H/R-stimulated H9c2 cells. Meanwhile, NRON knockdown also significantly attenuated heart damage and improved cardiac function in an AMI mouse model. Furthermore, compared with si-normal control, NRON knockdown increased the levels of HIF-1α, p-AKT, p-mTOR, and p-ERK1/2. HIF-1α knockdown reversed the effects of NRON knockdown in H/R-stimulated-H9c2 cells damage. Overall, our study revealed that NRON knockdown alleviated H/R-induced cardiomyocyte apoptosis by upregulating HIF-1α expression, suggesting that NRON might be a novel therapeutic target for AMI.
Add-on Therapy With Sacubitril/Valsartan and Clinical Outcomes in CRT-D Nonresponder Patients
Authors: Russo Vincenzo , Ammendola Ernesto , Gasperetti Alessio , Bottino Roberta , Schiavone Marco , Masarone Daniele , Pacileo Giuseppe , Nigro Gerardo , Golino Paolo , Lip Gregory Y. H. , D'Andrea Antonello , Boriani Giuseppe , Proietti Riccardo
Published: December 2021

No data on the add-on sacubitril/valsartan (S/V) therapy among cardiac resynchronization therapy with a defibrillator (CRT-D) nonresponder patients are currently available in literature. We conducted a prospective observational study including 190 CRT-D nonresponder patients with symptomatic heart failure with reduced ejection fraction despite the optimal medical therapy from at least 1 year. The primary endpoint was the rate of additional responders (left ventricular end-systolic volume reduction >15%) at 12 months from the introduction of S/V therapy. At the end of the 12 months follow-up, 37 patients (19.5%) were deemed as “additional responders” to the combination use of CRT + S/V therapy. The only clinical predictor of additional response was a lower left ventricular ejection fraction [OR 0.881 (0.815–0.953), P = 0.002] at baseline. At 12 months follow-up, there were significant improvements in heart failure (HF) symptoms and functional status [New York Heart Association 2 (2–3) vs. 1 (1–2), P < 0.001; physical activity duration/day: 10 (8–12) vs. 13 (10–18) hours, P < 0.001]. Compared with the 12 months preceding S/V introduction, there were significant reductions in the rate of HF rehospitalization (35.5% vs. 19.5%, P < 0.001), in atrial tachycardia/atrial fibrillation burden [6.0 (5.0–8.0) % vs. 0 (0–2.0) %, P < 0.001] and in the proportions of patients experiencing ventricular arrhythmias (21.6% vs. 6.3%; P < 0.001). Our results indicate that S/V add-on therapy in CRT-D nonresponder patients is associated with 19.5% of additional responders, a reduction in HF symptoms and rehospitalizations, AF burden, and ventricular arrhythmias.
Technical Aspects of Flow Cytometry-based Measurable Residual Disease Quantification in Acute Myeloid Leukemia: Experience of the European LeukemiaNet MRD Working Party
Authors: Tettero Jesse M. , Freeman Sylvie , Buecklein Veit , Venditti Adriano , Maurillo Luca , Kern Wolfgang , Walter Roland B. , Wood Brent L. , Roumier Christophe , Philippé Jan , Denys Barbara , Jorgensen Jeffrey L. , Bene Marie C. , Lacombe Francis , Plesa Adriana , Guzman Monica L. , Wierzbowska Agnieszka , Czyz Anna , Ngai Lok Lam , Schwarzer Adrian , Bachas Costa , Cloos Jacqueline , Subklewe Marion , Fuering-Buske Michaela , Buccisano Francesco
Published: December 2021

Measurable residual disease (MRD) quantified by multiparameter flow cytometry (MFC) is a strong and independent prognostic factor in acute myeloid leukemia (AML). However, several technical factors may affect the final read-out of the assay. Experts from the MRD Working Party of the European LeukemiaNet evaluated which aspects are crucial for accurate MFC-MRD measurement. Here, we report on the agreement, obtained via a combination of a cross-sectional questionnaire, live discussions, and a Delphi poll. The recommendations consist of several key issues from bone marrow sampling to final laboratory reporting to ensure quality and reproducibility of results. Furthermore, the experiences were tested by comparing two 8-color MRD panels in multiple laboratories. The results presented here underscore the feasibility and the utility of a harmonized theoretical and practical MFC-MRD assessment and are a next step toward further harmonization.
Recordkeeping Error or Strategic Seasonal Substitution?
Authors: Raymond Benjamin
Published: December 2021

Objective:

I compare the seasonal patterns observed in the Survey of Occupational Injuries and Illnesses (SOII) to claims data from the IBM® MarketScan® Research Databases.

Methods:

I construct monthly injury rates and claims rates by supplementing occupational injuries and other claims data with hours data from the Current Population Survey and estimate seasonal effects using an Unobservable Components Model.

Results:

While workers’ compensation data and the SOII display similar seasonal patterns, the year-end decline in the MarketScan data is 1/3 to 1/2 the magnitude observed in the SOII. Short-term disability and private health insurance claims display seasonal patterns inversely related to occupational injuries.

Conclusions:

Part of the year-end decline in occupational injuries observed in the SOII is likely due to recordkeeping error. There is also some evidence of strategic seasonal substitution between various health-compensation alternatives.
Effects of Sleep, Exercise, and Leadership Support on Resilience in Frontline Healthcare Workers During the COVID-19 Pandemic
Authors: Kaye-Kauderer Halley , Loo George , Murrough James W. , Feingold Jordyn H. , Feder Adriana , Peccoralo Lauren , Ripp Jonathan , Pietrzak Robert H.
Published: December 2021

Objective:

To evaluate the direct and interacting effects of personal and systemic factors that contribute to psychological distress among frontline healthcare workers (FHCWs) during the COVID-19 pandemic.

Methods:

Data were collected using a hospital-wide, cross-sectional survey. A multivariable binary logistic regression and relative importance analysis was conducted to identify factors associated with screening positive for C19-distress.

Results:

A total of 1005 (39.0%, 95%CI - 37.1–40.9%) out of 2579 FHCWs met the prespecified cutoff values for significant symptoms of C19-distress. Fewer sleep hours and lower perceptions of leadership support explained the majority of variance (19.4% relative variance explained [RVE]) in C19-distress, followed by team camaraderie (6.4% RVE), physical exercise (4.9% RVE), and engagement in hobbies (3.2% RVE).

Conclusion:

These results underscore the importance of restorative behaviors as potential targets to help decrease distress and promote resilience in FHCWs.
The Effect of Abuse and Mistreatment on Healthcare Providers (TEAM)
Authors: Pinkhasov Aaron , Filangieri Carole , Rzeszut Mary , Wilkenfeld Marc , Akerman Meredith , Divers Jasmin , Oliveras Jessica , Bostwick J. Michael , Svoronos Alexander , Peltier Morgan R.
Published: December 2021

Objective:

Aggression from patients and families on health care providers (HCP) is common yet understudied. We measured its prevalence and impact on HCPs in inpatient and outpatient settings.

Methods:

Four thousand six hundred seven HCPs employed by a community teaching hospital received an anonymous survey with results analyzed.

Results:

Of 1609 HCPs (35%) completing the survey, 88% of inpatient staff reported experiencing different types of aggression compared to 82% in outpatient setting. Almost half did not report it to their supervisor. Younger staff were more likely to report abuse. Negative impacts on productivity and patient care were reported. A third of all responders’ indicated negative effects on mental health.

Conclusions:

Despite negative impacts on staff wellbeing and productivity, patient/family aggression toward HCPs is highly prevalent and underreported. Our healthcare system needs measures to address staff security and wellness.
Do Not Forget About the Ticks: An Unusual Cause of Fever, GI Distress, and Cytopenias in a Child With ALL
Authors: Ungar Stephanie P. , Varkey Joyce , Pierro Joanna , Raetz Elizabeth , Ratner Adam J.
Published: December 2021

We report the case of a 5-year-old male with B-cell acute lymphoblastic leukemia in remission, receiving maintenance chemotherapy, who presented with fever, emesis, diarrhea, headache, and lethargy. He developed rapidly progressive cytopenias and was found to have acute human granulocytic anaplasmosis as well as evidence of past infection with Babesia microti. The case highlights the need to maintain a broad differential for infection in children undergoing chemotherapy or other immunosuppressive therapies with possible or known tick exposure.
Fludarabine-based Reduced Intensity Conditioning for Allogeneic Hematopoietic Stem Cell Transplantation in a Pediatric Patient With Bone Marrow Failure Syndrome Type 3
Authors: Barhoom Dima , Mohseni Rashin , Behfar Maryam , Hamidieh Amir A.
Published: December 2021

Bone marrow failure syndrome (BMFS) type 3 is a rare genetic heterogeneous disorder, considered to be one of Inherited BMFSs related to ribosomopathies. It caused by a novel Homozygous variant in DNAJC21 gene, which affects cytoplasmic maturation of 60S ribosomal, leading to increase cell death, and inhibits cellular proliferation causing shwachman-diamond Syndrome-like syndrome. Only 15 cases of BMFS type 3 have been published in the literature. Therefore, the full phenotypic spectrum and the experience of hematopoietic stem cell transplantation (HSCT) are limited. Herein, we report an uncomplicated HSCT from human leukocyte antigen-identical sibling for a BMFS-3 patient at 22 months of age, who suffered from chronic diarrhea, severe failure to thrive and cytopenia required transfusions. We used a reduced intensity conditioning regimen including fludarabine, low-dose cyclophosphamide, and antithymocyte globulin with cyclosporine for prevent graft versus host disease. This regimen was safe and sufficient to achieve rapid engraftment without significant toxicity. Although, Mixed chimerism between 80% and 90% was observed since day +30, she gained 2 kg during 12 months post-transplant and no need for transfusions has been reported any more. Thus, we recommend HSCT with fludarabine-based reduced intensity conditioning regimen in this syndrome as progressive cytopenia occurs and an human leukocyte antigen-matched family donor is available.
Persistent Symptoms, Lyme Disease, and Prior Trauma
Authors: Mustafiz Fayel , Moeller James , Kuvaldina Maria , Bennett Clair , Fallon Brian A.
Published: December 2021

One prior study suggests that traumatic events before Lyme disease play an important role in symptom severity. We examined this hypothesis among 60 individuals with persistent symptoms after Lyme disease using validated measures of trauma history, mental and physical symptoms, and functional status. Analysis of variance with Tukey-Kramer multiple comparisons test revealed that a greater number of traumatic events were significantly associated with greater symptom severity on the scales of mood (stress, depression, and anxiety), cognition, multisystem symptom burden, and functional status (mental and physical), but not on measures of pain and fatigue. The effect sizes—meaningful but not large (0.17–0.29)—were mostly produced by comparison with individuals reporting multiple prior traumatic events, representing half of the posttreatment Lyme disease syndrome (PTLDS) group. In conclusion, although PTLDS may be exacerbated by past trauma, trauma plays a role in only a subgroup of PTLDS. Whether addressing prior trauma can improve outcomes in this subgroup requires study.
A Stroke Alert With Unexpected Outcome
Authors: Gritsch David , Harahsheh Ehab , Mbonde Amir , Mangipudi Kartik , Dawit Sara , Noe Katherine H. , Demaerschalk Bart M.
Published: December 2021

Introduction:

Observational studies have suggested that intravenous (IV) thrombolysis may be unfavorable in patients with high-grade gliomas. However, current literature on thrombolysis outcomes in patients with primary brain tumors is largely limited to case reports and may be influenced by publication bias.

Case Report:

A 69-year-old male presented with acute left hemiplegia, left hemisensory loss, neglect, dysarthria and right gaze preference (National Institutes of Health Stroke Scale 22). An emergent noncontrast head computerized tomography showed hypoattenuation in the right parietal lobe of unclear chronicity and IV thrombolysis with tissue plasminogen activator was administered within the 4.5 hour window. Following IV thrombolysis, a computerized tomography angiogram of the head and neck revealed no large vessel occlusion. However, a marginally enhancing, and centrally nonenhancing mass within the right parietal lobe associated with vasogenic edema was elucidated. Subsequently, the patient developed abnormal left hemibody tonic-clonic motor activity, left gaze preference and left-beating nystagmus concerning for focal motor status epilepticus. An emergent electroencephalogram, following administration of IV levetiracetam, showed right hemispheric electrographic seizures and right hemispheric periodic lateralized epileptiform discharges. Brain magnetic resonance imaging with gadolinium revealed 2.5 cm ring-enhancing mass in the right parietal lobe. The patient underwent right sided craniotomy with resection of the mass and pathology revealed Glioblastoma.

Conclusion:

We report a case of thrombolysis administered in a patient with high-grade glioma with no apparent complications.
Split Buccal Fat Flap in Modified Furlow Palatoplasty: Surgical Technique and Early Result
Authors: Denadai Rafael , Lo Lun-Jou
Published: December 2021

Encouraging results have been described for the use of pedicled buccal fat pad flap in primary cleft palate repair. This retrospective study describes the surgical technique and early results of a technical innovation utilizing the split buccal fat flaps in modified Furlow palatoplasty with small double-opposing Z-plasty. This technique introduces buccal fat tissue for coverage of lateral denuded palate surfaces to reduce the bone exposure and scar formation to potentially attenuate maxillary growth interference and for reinforcement of the palatal areas of high tension or with incomplete closure to decrease the risk of postoperative dehiscence and oronasal fistula formation. Consecutive nonsyndromic patients (n = 56) with cleft palate were treated with this method, all of whom demonstrated fast mucosalization of lateral palatal recipient regions within 3 weeks postoperatively and showed no fistula with 12 months’ follow-up. Of 19 patients (33.9 percent) who underwent auditory-perceptual assessment, 15 (78.9 percent) had normal resonance. Surgeons could add this alternative surgical maneuver to their armamentarium during the primary palatoplasty, in which coverage of lateral surfaces and reinforcement with fat tissue in the anterior soft palate space are of paramount relevance.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Quantitative Morphologic Analysis of Cranial Vault in Twist1 +/− Mice: Implications in Craniosynostosis
Authors: Nuri Takashi , Ota Masato , Ueda Koichi , Iseki Sachiko
Published: December 2021

Background:

The haploinsufficiency in the TWIST1 gene encoding a basic helix-loop-helix transcription factor is a cause of one of the craniosynostosis syndromes, Saethre-Chotzen syndrome. Patients with craniosynostosis usually require operative release of affected sutures, which makes it difficult to observe the long-term consequence of suture fusion on craniofacial growth.

Methods:

In this study, we performed quantitative analysis of morphologic changes of the skull in Twist1 heterozygously–deleted mice (Twist1
+/−) with micro–computed tomographic images.

Results:

In Twist1
+/− mice, fusion of the coronal suture began before postnatal day 14 and progressed until postnatal day 56, during which morphologic changes occurred. The growth of the skull was not achieved by a constant increase in the measured distances in wild type mice; some distances in the top-basal axis were decreased during the observation period. In the Twist1
+/− mouse, growth in the top-basal axis was accelerated and that of the frontal cranium was reduced. In the unicoronal suture fusion mouse, the length of the zygomatic arch of affected side was shorter in the Twist1
+/− mouse. In one postnatal day 56 Twist1
+/− mouse with bilateral coronal suture fusion, asymmetric zygomatic arch length was identified.

Conclusion:

The authors’results suggest that measuring the length of the left and right zygomatic arches may be useful for early diagnosis of coronal suture fusion and for estimation of the timing of synostosis, and that more detailed study on the growth pattern of the normal and the synostosed skull could provide prediction of the risk of resynostosis.

Clinical Relevance Statement:

The data from this study can be useful to better understand the cranial growth pattern in patients with craniosynostosis.
Stress-Related Inflammation and Social Withdrawal in Mothers of a Child With Cancer: A 1-Year Follow-Up Study
Authors: Lindsay Emily K. , Inagaki Tristen K. , Walsh Catherine P. , Messay Berhane , Ewing Linda J. , Marsland Anna L.
Published: December 2021

Objective

Acute inflammation-induced sickness behavior involves changes in social behavior that are believed to promote recovery. Whether chronic inflammation can influence social behaviors in ways that promote recovery is unknown. In a sample of mothers of a child with cancer, this report explores the relationship between inflammation that accompanies the stress of diagnosis and changes in social network, cancer-related stress, and inflammation across 1 year. Three hypotheses tested whether a) initial levels of stress associate with initial levels of inflammation, b) initial levels of inflammation predict social network changes over time, and c) social network changes over time buffer changes in stress and inflammation over time.

Methods

Cancer-related stress (Impact of Events Scale), social network (social roles and contacts from the Social Network Inventory), and systemic inflammation (circulating interleukin [IL]-6) were assessed in 120 mothers three times after their child’s cancer diagnosis: after diagnosis (T1), 6-month follow-up (T2), and 12-month follow-up (T3).

Results

Consistent with predictions, greater cancer-related stress after diagnosis (T1) was associated with higher IL-6 after diagnosis (T1; b = 0.014, standard error [SE] = 0.01, p = .008). In turn, higher IL-6 after diagnosis (T1) was associated with a decrease in social roles over time (T1 ➔ T3; B = −0.030, SE = 0.01, p = .041). Finally, dropping social roles over time (T1 ➔ T3) was associated with decreases in cancer-related stress (B = 25.44, SE = 12.31, p = .039) and slower increases in IL-6 (B = 1.06, SE = 0.52, p = .040) over time.

Conclusions

This study provides a first indication that chronic stress–related systemic inflammation may predict changes in social behavior that associate with stress recovery and slower increases in inflammation in the year after a major life stressor.
Robert McNeill Alexander. 7 July 1934—21 March 2016
Authors: Alexander Gordon
Published: December 2021

Neill Alexander graduated in natural sciences at the University of Cambridge in 1955. After a PhD at Cambridge and a lecturership at the University College of North Wales in Bangor, he was appointed to the chair of the Department of Pure and Applied Zoology at the University of Leeds in 1969. At that stage, he switched his research interests abruptly from fishes to the mechanics of legged locomotion. He conducted experiments with a variety of mammals, calculating forces, stresses and strains in muscle fibres, bones and tendons. His speciality became the application of mathematical models to animal locomotion, including repurposing the Froude number, devised by the Victorian engineer William Froude (FRS 1870) for use with ships, to estimate the speed of dinosaurs based on the spacing of their fossil footprints. Subsequent work included modelling the optimization of mammal performance and the minimization of energy costs. In 1992, following an announcement that London Zoo would have to close as a result of shortage of funds, Neill was appointed secretary of the Zoological Society of London. During the period of his secretaryship, the Society's finances recovered, with both its zoos (London and Whipsnade) breaking even in 1993 and the Society returning a surplus in each subsequent year. Neill was awarded the CBE in 2000. The National Portrait Gallery holds his portrait by John Arnison.