bluuebunny/crossref_metadata_2025 huggingface dataset:
Salt-induced first-order structural transition in a DNA-interacting protein
Authors: Lu Yue , Lu Ying , Ma Jianbing , Li Jinghua , Huang Xingyuan , Jia Qi , Ma Dongfei , Liu Ming , Zhang Hao , Yu Xuan , Hu Shuxin , Li Yunliang , Xu Chunhua , Li Ming
Published: April 2021

Thermodynamics and structural transitions on protein surfaces remain relatively understudied and poorly understood. Wrapping of DNA on proteins provides a paradigm for studying protein surfaces. We used magnetic tweezers to investigate a prototypical DNA-interacting protein, i.e., the single-stranded DNA binding protein (SSB). SSB binds DNA with distinct binding modes the mechanism of which is still elusive. The measured thermodynamic parameters relevant to the SSB-DNA complex are salt-dependent and discontinuous at the bind-mode transitions. Our data indicate that free SSB undergoes salt-induced first-order structural transitions. The conclusion was supported by the infrared spectroscopy of SSB in salt solutions. Ultrafast infrared spectroscopy further suggests that the transitions are correlated with surface salt bridges. Our work not only unravels a long-standing mystery of the different binding site sizes of SSB, but also would inspire interests in thermodynamics of protein surfaces.
Discovery of a Covalent FEM1B Recruiter for Targeted Protein Degradation Applications
Authors: Henning Nathaniel J. , Manford Andrew G. , Spradlin Jessica N. , Brittain Scott M. , McKenna Jeffrey M. , Tallarico John A. , Schirle Markus , Rape Michael , Nomura Daniel K.
Published: April 2021

Proteolysis Targeting Chimeras (PROTACs), heterobifunctional compounds that consist of protein-targeting ligands linked to an E3 ligase recruiter, have arisen as a powerful therapeutic modality for targeted protein degradation (TPD). Despite the popularity of TPD approaches in drug discovery, only a small number of E3 ligase recruiters are available for the >600 E3 ligases that exist in human cells. Here, we have discovered a cysteine-reactive covalent ligand, EN106, that targets FEM1B, an E3 ligase recently discovered as the critical component of the cellular response to reductive stress. By targeting Cys186 in FEM1B, EN106 disrupts recognition of the key reductive stress substrate of FEM1B, FNIP1. We further establish that EN106 can be used as a covalent recruiter for FEM1B in TPD applications, in which we demonstrate that a PROTAC linking EN106 to the BET Bromodomain inhibitor JQ1 leads to specific FEM1B- and proteasome-dependent degradation of BRD4 in cells. Our study showcases a covalent ligand that targets a natural E3 ligase-substrate binding site and highlights the utility of covalent ligand screening in expanding the arsenal of E3 ligase recruiters that can be deployed for TPD applications.
Dendritic inhibition by Shh signaling-dependent stellate cell pool is critical for motor learning
Authors: Li Wen , Chen Lei , Fleming Jonathan T. , Brignola Emily , Zavalin Kirill , Lagrange Andre H. , Rex Tonia S. , Heiney Shane A. , Wojaczynski Gregory J. , Medina Javier F. , Chiang Chin
Published: April 2021

Cerebellar inhibitory interneurons are important regulators of neural circuit activity for diverse motor and non-motor functions. The molecular layer interneurons (MLI), consisting of basket cells (BCs) and stellate cells (SCs), provide dendritic and somatic inhibitory synapses onto Purkinje cells, respectively. They are sequentially generated in an inside-out pattern from Pax2+ immature interneurons which migrate from the prospective white matter to the ML of the cortex. However, little is known as to how MLI subtype identities and pool sizes are determined, nor are their contributions to motor learning well understood. Here, we show that GABAergic progenitors fated to generate both BCs and SCs respond to the Shh signal. Conditional abrogation of Shh signaling inhibited proliferation of GABAergic progenitors and reduced the number of Pax2+cells, whereas persistent Shh pathway activation increased their numbers. These changes, however, did not affect early-born BC numbers but selectively altered the SC pool size. Moreover, genetic depletion of GABAergic progenitors when BCs are actively generated also resulted in a specific reduction of SCs, suggesting that the specification of MLI subtypes is independent of Shh signaling and their birth order and likely occurs after Pax2+cells settle into their laminar positions in an inside-out sequence. Mutant mice with reduced SC numbers displayed decreased dendritic inhibitory synapses and neurotransmission onto Purkinje cells, resulting in an impaired acquisition of eyeblink conditioning. These findings also reveal an essential role of Shh signaling-dependent SCs in regulating inhibitory dendritic synapses and motor learning.
Short‐term multimodal prehabilitation improves functional capacity for colorectal cancer patients prior to surgery
Authors: Suen Michael , Liew Andre , Turner Jane D. , Khatri Sonia , Lin Yanlan , Raso Kristy L. , Vardy Janette L.
Published: April 2021

Aim

Evaluate feasibility and outcomes of a multimodal prehabiliation program in patients with stage I‐III colorectal cancer (CRC) awaiting surgery.

Methods

Patients scheduled for elective CRC resection at Concord Repatriation General Hospital were recruited from pre‐admission clinic between January and November 2018. Participants received a 2‐4 week prehabilitation program consisting of supervised exercise sessions, nurse‐led phone support, and written nutritional information. Participants were assessed at baseline, pre‐surgery, and 4 weeks post‐surgery.

Results

Twenty‐two patients participated in the program: 55% male; median age 73 (56‐86) years. Six (28%) required an interpreter. At baseline, 19 of 22 (86%) had at least one comorbidity. Median intervention length was 11.5 days (range 7‐29). Participants attended 79% of scheduled exercise sessions (range 33‐100%, mean 3.5 sessions) and 66% of nurse support calls (range 0‐100%, mean 2.6 sessions). Between baseline and pre‐surgery, participants reported increasing mean unsupervised moderate‐intensity aerobic exercise from 17 (range 0‐210) to 73 minutes/week (range 0–276) and mean vigorous‐intensity aerobic exercise from 0 to 24 minutes/week (range 0‐300). Resistance exercise sessions increased from 0.6 to 2.6 times/week. Mean 6‐minute walk test distance increased by 48 meters (435‐483 m) and 30‐second "sit to stand" by 1.6 repetitions. Small improvements were seen in global quality of life and fatigue. Nutritional status and body composition remained unchanged. All participants were satisfied/strongly satisfied with the program and would recommend it to others.

Conclusion

Our multimodal prehabilitation program was feasible in CRC patients inclusive of those from non‐English speaking backgrounds, with improvement in functional capacity before CRC surgery.
Incorporation of eribulin in the systemic treatment of metastatic breast cancer patients in Australia
Authors: Chan Arlene , Lomma Christopher , Chih HuiJun , Blackely Elizabeth , Woodward Natasha , Tsoi Daphne , Cheong Kerry , Chipman Mitchell , Redfern Andrew
Published: April 2021

Purpose

Review of utilization and efficacy of eribulin in Australian metastatic breast cancer (MBC) patients.

Methods

Retrospective review of consecutive MBC patients treated with eribulin in tertiary Australian BC centers. Key inclusion criteria included eribulin administration in nonclinical trial setting from October 2014 onwards, known duration of MBC systemic treatments administered and known follow‐up date after eribulin. Cox regression model was used to assess survival.

Results

Study population comprised 266 patients from eight centers treated between October 2014 and May 2018. Median age at time of MBC diagnosis was 54 years with 18% of patients having de novo MBC. Seventy‐six percent had hormone receptor positive (HRp) disease, 19% triple negative (TN) and 5% HER2‐positive. CNS involvement was present in 36% of patients. Eribulin was most frequently given as third‐line chemotherapy (36%), with no prior anthracycline exposure in 14% of total population. Eribulin was given more frequently as ≤third‐line chemotherapy than > third‐line in patients with TN disease, ≥ two metastatic sites or CNS disease. Median overall survival (OS) from eribulin administration was 9.2 (95% CI [8.0, 10.3]) months.

Conclusion

Similar efficacy was demonstrated for eribulin when given in the first‐line to beyond the fifth line of chemotherapy in all subtypes of MBC.
A prospective, real‐world, clinical pharmacokinetic study to inform lacosamide dosing in critically ill patients undergoing continuous venovenous haemofiltration (PADRE‐02)
Authors: Kalaria Shamir N. , Armahizer Michael , McCarthy Paul , Badjatia Neeraj , Gobburu Jogarao V. , Gopalakrishnan Mathangi
Published: April 2021

Aims

Although the use of continuous renal replacement therapy (CRRT) has increased, limited dosing information exists on the effect of CRRT on antiepileptic drug pharmacokinetics. The objectives of this practice‐based study are to evaluate the pharmacokinetics of lacosamide and recommend individualized dosing recommendations in critically ill patients receiving continuous venovenous haemofiltration (CVVH).

Methods

Seven patients receiving lacosamide and CVVH in a neurocritical care unit were enrolled. Pre‐filter, post‐filter and ultrafiltrate samples were obtained at baseline, right after the completion of the infusion, and up to six additional sampling time points post‐administration. Patient‐specific flow rates and clinical measures were also collected simultaneously at the time of sampling. Plasma concentrations were measured using a validated high‐performance liquid chromatography with ultraviolet radiation detection (HPLC‐UV) bioanalytical method. Non‐compartmental analysis was utilized to characterize the pharmacokinetics of lacosamide.

Results

The observed mean sieving coefficient for lacosamide was 0.80 ± 0.10, suggesting high removal of lacosamide. Concentrations measured in six out of seven patients were observed to be outside the therapeutic range (5–12 mg/L). The estimated average volume of distribution was found to be similar to healthy patients (0.58 L/kg). The mean bias and precision of the estimated total clearance was −2.53% and 14.9%, respectively. Simulations of various doses suggest that effluent flow rate‐based dosing regimens could be used to individualize lacosamide therapeutics.

Conclusions

CVVH clearance contributed a major fraction of the total lacosamide clearance in neurocritically ill patients. Given that drug clearance increases with higher effluent flow rates, lacosamide dosing regimens should be increased to match exposures observed in patients with normal renal function.
Economic evaluation of remdesivir for the treatment of severe COVID‐19 patients in China under different scenarios
Authors: Jiang Yawen , Cai Dan , Chen Daqin , Jiang Shan , Si Lei , Wu Jing
Published: April 2021

Aims

The present study aimed to evaluate the cost‐effectiveness of the 5‐day remdesivir regimen compared with standard of care among severe COVID‐19 patients in China, the evidence on which is essential to inform the necessity of securing access to remdesivir.

Methods

A dynamic transmission model that extended the susceptible–exposed–infected–recovered framework by incorporating asymptomatic, presymptomatic and waiting‐to‐be‐diagnosed patients was constructed to conduct the cost‐effectiveness analysis from the healthcare system perspective. To estimate epidemic parameters, the model was first calibrated to the observed epidemic curve in Wuhan from 23 January to 19 March 2020. Following the calibration, the infected compartment was replaced by 3 severity‐defined health states to reflect differential costs and quality of life associated with disease gravity. Costs and quality‐adjusted life year (QALY) outcomes of 9 million simulated people were accrued across time to evaluate the incremental cost‐effectiveness ratio of remdesivir. As robustness checks, an alternative modelling technique using decision tree, additional epidemic scenarios representing different epidemic intensities, and 1‐way parameter variations were also analysed.

Results

Remdesivir treatment cost CN¥97.93 million more than standard of care. Also, the net QALY gain from 5‐day remdesivir treatment was 6947 QALYs. As such, the incremental cost‐effectiveness ratio was CN¥14 098/QALY, substantially lower than the gross domestic product per capita threshold. The peak daily number of severe cases was 19% lower in the remdesivir treatment strategy. Overall, results were robust in alternative scenarios and sensitivity analyses.

Conclusion

Given the cost‐effectiveness profile, access to remdesivir for severe COVID‐19 patients in China should be considered.
Excellent overall and chronic graft‐versus‐host‐disease‐free event‐free survival in Fanconi anaemia patients undergoing matched related‐ and unrelated‐donor bone marrow transplantation using alemtuzumab–Flu–Cy: the UK experience
Authors: Bernard Fanette , Uppugunduri Chakradhara Rao S , Meyer Stefan , Cummins Michelle , Patrick Katharine , James Beki , Skinner Roderick , Tewari Sanjay , Carpenter Ben , Wynn Robert , Veys Paul , Amrolia Persis ,   the UK Paediatric BMT group
Published: April 2021

Haematopoietic stem cell transplantation (HSCT) remains the only curative option in Fanconi anaemia (FA). We analysed the outcome of children transplanted for FA between 1999 and 2018 in the UK. A total of 94 transplants were performed in 82 patients. Among the donors, 51·2% were matched related donors (MRD) while the remainder were alternative donors. Most patients received a fludarabine–cyclophosphamide (Flu–Cy)‐based conditioning regimen (86·6%) and in vivo T‐cell depletion with alemtuzumab (69·5%). Five‐year overall survival (OS) was 85·4% [70·4–93.2] with MRD, 95·7% [72·9–99.4] with matched unrelated donors (MUD), 44·4% [6·6–78.5] with mismatched unrelated donors (MMUD) and 44·4% [13·6–71.9] with mismatched related donors (MMRD) (P < 0·001). Other factors significantly impacting OS were pre‐transplant bone marrow status, source of stem cells, cytomegalovirus (CMV) serostatus, preparation with Flu–Cy, use of total body irradiation (TBI) and alemtuzumab as serotherapy. In multivariate analysis, absence of myelodysplastic syndrome (MDS) or leukaemia, bone marrow as source of stem cells, cytomegalovirus (CMV) other than +/− (Recipient/Donor) and Flu–Cy were protective factors for five‐year OS. Five‐year chronic graft‐versus‐host‐disease (cGVHD)‐free event‐free survival was 75·4% with the same risk factors except for CMV serostatus. Five‐year non‐relapse mortality was 13·8% [7·3–22.3]. Only five patients (6·1%) developed grade II–IV acute GVHD and two patients chronic GVHD. These data confirm the excellent outcome of matched related or unrelated HSCT in children with FA.
Family cohesion and attention deficit exert an influence on visits to the dentist in early adolescence
Authors: Moura Mirella de Fátima Liberato de , Firmino Ramon Targino , Neves Érick Tássio Barbosa , Paiva Saul Martins , Ferreira Fernanda Morais , Granville‐Garcia Ana Flávia
Published: April 2021

Objectives

To determine whether family environment, signs of attention deficit/hyperactivity disorder (ADHD) and oral health literacy (OHL) are associated with visits to the dentist in adolescents.

Methods

A school‐based cross‐sectional study was conducted with a representative sample of 448 12‐year‐old adolescents enrolled at schools in the city of Cajazeiras, Brazil. The adolescents answered a validated questionnaire addressing family cohesion and adaptability (FACES III), an OHL measure (Brazilian Rapid Estimate of Adult Literacy in Dentistry [BREALD‐30]) and a questionnaire addressing the history of visits to the dentist and previous toothache experience. The parents answered a questionnaire addressing sociodemographic characteristics. Parents and teachers answered the inattention and hyperactivity/impulsivity subscales of the Swanson, Nolan & Pelham (SNAP‐IV) questionnaire for the detection of signs of ADHD. Multiple Poisson regression with robust variance was used for data analysis (α = 5%).

Results

The prevalence of having visited a dentist some time in life was higher among adolescents with enmeshed (PR = 1.08; 95% CI: 1.01‐1.15) and connected (PR = 1.06; 95% CI: 1.01‐1.13) families and those with attention deficit according to parents' reports (PR = 1.09; 95% CI: 1.04‐1.14). A family income higher than the Brazilian minimum wage (PR = 1.06; 95% CI: 1.01‐1.12) and toothache in the previous six months (PR = 1.05; 95% CI: 1.01‐1.11) were also associated with the outcome.

Conclusion

Family cohesion and attention deficit according to parental reports influenced visits to the dentist among adolescents. In contrast, OHL was not associated with the outcome.
Heterogeneous price effects and increased price dispersion from quantity‐based congestion management
Authors: Lee Sunhyung , Liu Zexuan , Yu Haojun
Published: April 2021

We examine the effects of quantity‐based approaches to airport congestion management such as slot restrictions on price dispersion and on‐time performance. From the evidence at Newark Liberty International Airport, we find that slot restrictions increase price dispersion and improve on‐time performance. Price dispersion originates from heterogeneous price effects, as ticket prices for high‐value passengers increase more than that for low‐value passengers. Our novel finding is that the share of passengers who have purchased tickets at a top‐end price increase despite the price hike. We use various empirical specifications and an analysis on leads and lags of the policy for robustness.
Cortico‐subcortical functional connectivity modifications in fatigued multiple sclerosis patients treated with fampridine and amantadine
Authors: Rocca Maria A. , Valsasina Paola , Colombo Bruno , Martinelli Vittorio , Filippi Massimo
Published: April 2021

Background and purpose

Fatigue in multiple sclerosis (MS) is common and disabling; medication efficacy is still not fully proven. The aim of this study was to investigate 4‐week modifications of fatigue severity in 45 relapsing‐remitting MS patients after different symptomatic treatments, and changes in concomitant resting state (RS) functional connectivity (FC).

Methods

Patients were randomly, blindly assigned to treatment with fampridine (n = 15), amantadine (n = 15) or placebo (n = 15), and underwent clinical assessment and 3‐Tesla RS functional magnetic resonance imaging at baseline (t0) and after 4 weeks (w4) of treatment. Fifteen healthy controls (HCs) were also studied. Changes in modified fatigue impact scale (MFIS) score and network RS FC were assessed.

Results

In MS, abnormalities of network RS FC at t0 did not differ between treatment groups and correlated with fatigue severity. At w4, global scores and subscores on the MFIS decreased in all groups, with no time‐by‐treatment interaction. At w4, all patient groups had changes in RS FC in several networks, with significant time‐by‐treatment interactions in basal ganglia, sensorimotor and default‐mode networks in fampridine‐treated patients versus the other groups, and in frontoparietal network in amantadine‐treated patients. In the fampridine group, RS FC changes correlated with concurrently decreased MFIS score (r range = −0.75 to 0.74, p range = 0.003–0.05).

Conclusions

Fatigue improved in all MS groups, independently of treatment. Concomitant RS FC modifications were located in sensorimotor, inferior frontal and subcortical regions for fampridine‐ and amantadine‐treated patients, and in associative sensory cortices for placebo‐treated patients.
The effects of exchange listing on market quality: Evidence from over‐the‐counter uplistings
Authors: Davis Ryan , Griffith Todd , Roseman Brian , Yildiz Serhat
Published: April 2021

We study the effects of exchange uplisting from the modern over‐the‐counter (OTC) markets on liquidity, volatility, and price discovery. In a series of difference‐in‐differences tests, we find that for a sample of OTC treatment firms that uplist to the NASDAQ, New York Stock Exchange (NYSE), or NYSE MKT, relative to matched control firms, liquidity improves dramatically after listing. We also show that price discovery improves for treatment firms vis‐à‐vis control firms after listing. The results contribute to the discussion surrounding the facilitation of capital formation and offer important insights to investors, managers, and exchange officials.
Tectonic setting and formation of the Setouchi volcanic rocks in the western Seto Inland Sea, Japan
Authors: Sato Daisuke , Haji Toshiki
Published: April 2021

The Setouchi volcanic rocks include high‐Mg andesites (HMAs) and garnet‐bearing dacite–rhyolite, and are sporadically distributed along the Median Tectonic Line, Japan. New U–Pb zircon ages and geological and geochemical data are presented for those rocks in the Western Setouchi region (W‐Setouchi). Previous studies referred to the altered andesite in the W‐Setouchi as “pre‐Setouchi volcanic rocks.” However, on the basis of the new U–Pb age (14.4 Ma ± 0.3 Ma) and geochemical characteristics, we redefine it as the Jikamuro Formation, part of the Setouchi volcanic rocks. Incompatible elements are more enriched in the Jikamuro Formation rocks than in the Setouchi HMAs. The characteristic element compositions may be explained by mixing of compositionally different magmas, including subducted sediment melts, plus a contribution from crustal contamination. A stress‐inversion technique with Bingham distribution method was applied to the orientations of felsic and mafic dikes within the Setouchi volcanic rocks, and indicates paleo‐stress conditions during the period of Setouchi volcanism in the W‐Setouchi. The analysis reveals NNW‐extensional stresses and a strike‐slip stress. We infer that the former represents extensional conditions during the main period of volcanism and the latter represents a stress transition during the most recent period of volcanism (after 12 Ma).
Laboratory simulation of longitudinally cracked teeth using the step‐stress cyclic loading method
Authors: Lin F. , Ordinola‐Zapata R. , Xu H. , Heo Y.C. , Fok A.
Published: April 2021

Aim

To simulate in a laboratory setting longitudinal cracking in root filled premolar teeth, using cyclic mechanical fatigue.

Methodology

Mesial‐occlusal‐distal (MOD) cavities were prepared in twenty root filled, single‐rooted, mandibular premolars restored with fibre posts and resin composites. The samples were randomly divided into two groups based on the loading approaches: static loading with a crosshead speed of 0.5 mm/min and step‐stress cyclic loading (1 Hz) with increasing amplitude. The loads and numbers of cycles to failure were recorded. Micro‐CT was also used to identify the fracture modes. Statistical analysis was performed using Student's t‐test. The level of significance was set at 0.05.

Results

The mean fracture loads for the static loading and cyclic loading groups were 769 ± 171 N and 720 ± 92 N, respectively. There was no significant difference between the two groups (P > 0.05). The proportions of longitudinal, cuspal and mixed‐mode fractures under cyclic loading were 50%, 20% and 30%, respectively. Longitudinal fractures occurred with larger numbers of cycles and higher average loads per cycle compared with the other fractures. Static loading produced only cuspal fractures.

Conclusions

Longitudinally cracked premolar teeth with root fillings were successfully produced using the step‐stress cyclic loading method. This provides a more clinically representative methodology for studying cracked teeth in a laboratory setting.
Heparin dosage, level, and resistance in SARS‐CoV2 infected patients in intensive care unit
Authors: Novelli Chiara , Borotto Erika , Beverina Ivo , Punzi Veronica , Radrizzani Danilo , Brando Bruno
Published: April 2021

Introduction

Patients with COVID‐19 frequently exhibit a hypercoagulable state with high thrombotic risk, particularly those admitted to intensive care units (ICU). Thromboprophylaxis is mandatory in these patients; nevertheless, thrombosis still occurs in many cases. Thus, the problem of assessing an adequate level of anticoagulation in ICU patients becomes evident during the COVID‐19 pandemic. The aim of this study was to evaluate the heparin resistance and the efficacy of heparin monitoring using an anti‐Xa activity assay.

Methods

Thirty‐seven heparin‐treated patients admitted to ICU for SARS‐CoV‐2 pneumonia were retrospectively studied for antifactor Xa activity (anti‐Xa), activated partial thromboplastin time (APTT), Antithrombin, Fibrinogen, D‐Dimer, Factor VIII, von Willebrand Factor, and the total daily amount of heparin administered. The correlation between APTT and anti‐Xa was evaluated for unfractionated heparins (UFH). The correlations between the daily dose of UFH or the dosage expressed as IU/kg b.w. for low molecular weight heparin (LMWH) and anti‐Xa were also evaluated.

Results

Twenty‐one patients received calcium heparin, 8 sodium heparin, and 8 LMWH. A moderate correlation was found between APTT and anti‐Xa for UFH. APTT did not correlate with coagulation parameters. 62% of UFH and 75% of LMWH treated patients were under the therapeutic range. About 75% of patients could be considered resistant to heparin.

Conclusions

SARS‐COV2 pneumonia patients in ICU have frequently heparin resistance. Anti‐Xa seems a more reliable method to monitor heparin treatment than APTT in acute patients, also because the assay is insensitive to the increased levels of fibrinogen, FVIII, and LAC that are common during the COVID‐19 inflammatory state.
Glass particle contamination threat in nursing practice: A pilot study
Authors: Erkoc Hut Arzu , Yazici Zihni A.
Published: April 2021

Aim

The aim of this study was to determine the level of glass particle contamination from medical ampoules during breakage in nursing practice and their removal by filtration.

Design

Glass medical ampoules were broken‐open as instructed and contamination was assessed microscopically.

Methods

Three types of medial ampoules (A, B, C) were used. Dispensation of contents was carried out using 21 or 22 G needles, with and without syringe‐filters. Particles were determined by light microscopy. This study was conducted between April 2018 and January 2020.

Results

Glass particles of 0.94–90.70 µm were detected in 94% of all samples. There were 48, 162 and 201 glass particles in groups, A, B and C, respectively. Filtration had no effect in group A but was effective up to 85% in the other groups.

Conclusion

This study confirms that ampoule contents are contaminated with glass particles during the opening procedure, which varies with make and content. Syringe‐filter use can be up to 85% effective in their removal.

Impact

Use of syringe‐filter can decrease glass particle contamination up to 85%. Innovative nursing studies are needed to minimize or completely avoid particule contamination.
A prospective evaluation of the impact of individual RF applications for slow pathway ablation for AVNRT: Markers of acute success
Authors: Sugumar Hariharan , Chieng David , Prabhu Sandeep , Voskoboinik Aleksandr , Anderson Robert D , Al‐Kaisey Ahmed , Lee Geoffrey , McLellan Alex J , Morton Joseph B , Taylor Andrew J , Ling Liang‐Han , Kalman Jonathan M , Kistler Peter M
Published: April 2021

Background

Catheter ablation is highly effective for atrioventricular nodal re‐entrant tachycardia (AVNRT). Generally junctional rhythm (JR) is an accepted requirement for successful ablation however there is a lack of detailed prospective studies to determine the characteristics of JR and the impact on slow pathway conduction.

Methods

Multicentre prospective observational study evaluating the impact of individual radiofrequency (RF) applications in typical AVNRT (slow/fast). Characteristics of JR during ablation were documented and detailed testing was performed after every RF application to determine outcome. Procedural success was defined as ≤1 AV nodal echo.

Results

Sixty‐seven patients were included (mean age 53 ± 18years, 57% female and a history of SVT 2.9 ± 4.7 years). RF (50w, 60°) ablation for AVNRT was applied in 301 locations with JR in 178 (59%). Successful slow pathway modification was achieved in 66 (99%) patients with slow pathway block in 30 (46%). Success was associated with JR in all patients. Success was achieved in six patients with RF < 10 s. There was no significant difference in the CL of JR during RF between effective (587 ± 150 ms) versus ineffective (611 ± 193 ms, p = .4) applications. Inadvertent junctional beat‐atrial (JA) block with immediate termination of RF was observed in 19 (28%) patients with AVNRT no longer inducible in 14 (74%). Freedom from SVT was achieved in 66 (99%) patients at a mean follow up of 15 ± 6 months.

Conclusion

In this prospective study, JR was required during RF for acute success in AVNRT. Cycle length of JR during RF was not predictive of success. Although unintended JA block during faster JR was associated with slow pathway block, this is a precursor to fast pathway block and should not be intentionally targeted.
Minimally decremental atriofascicular accessory pathway with bidirectional conduction
Authors: Vijayaraman Pugazhendhi
Published: April 2021

Atriofacicular pathways of Mahaim type are typically decrementally conducting accessory pathways without retrograde conduction properties, located on the right ventricular free wall at the tricuspid annulus. We report a patient with an atriofascicular pathway with minimal anterograde decremental conduction. Both long and short V‐H antidromic atriofascicular reentrant tachycardias were induced and mechanism confirmed with electrophysiologic testing. Additionally, orthodromic atriofascicular reentrant tachycardia with narrow and right bundle branch block morphologies were inducible. Mahaim pathway was successfully ablated with elimination of both antidromic and orthodromic tachycardias.
Twists and turns of land reform in Latin America: From predatory to intermediate states?
Authors: Botella‐Rodríguez Elisa , González‐Esteban Ángel Luis
Published: April 2021

Land reform has significantly evolved over time in Latin America. In the early decades of the 20th century, the ‘agrarian question’ involved different national paths of agrarian capitalism and their contributions to industrialization. Later in the century, agriculture played a secondary role, while market‐led reforms were implemented from the early 1990s in the region. The agrarian question is now related to a new range of global and national inequalities, whereas the land problem remains unresolved. This paper deals with the role of the state and social dynamics in understanding the twists and turns of Latin America's land reforms from the 1900s to the Global Era.
Multiple meanings of history in restoration
Authors: Case Madelon F. , Hallett Lauren M.
Published: April 2021

In ecological restoration, the role ofhistorical fidelityin restoration references has long been both a foundational concept and a frequent source of debate. However, this is not the only role that history plays. History in the sense ofhistorical knowledgecan inform goal‐setting and provide tools for success. History in the sense ofhistorical events(what has happened in a place) in many ways determines the goals and trajectories of restoration, and to what extent a historical reference is knowable and applicable. Here, we discuss a conceptual framework for how these forms of “history” interact, and particularly the underappreciated ways in which historical events shape the aspirations and limitations of restoration. We propose that considering legacies of historical events in the who, when, and where of restoration will be crucial to informing appropriate restoration goals for the future.
A successful method of transplanting adult Ecklonia radiata kelp, and relevance to other habitat‐forming macroalgae
Authors: Layton Cayne , Cameron Matthew J. , Shelamoff Victor , Tatsumi Masayuki , Wright Jeffrey T. , Johnson Craig R.
Published: April 2021

The ability to successfully transplant adult kelp has applications not only for ecological experiments, but also for habitat conservation and restoration projects. However, approaches to the long‐term transplanting of adult kelp (especially for stalked or ‘stipitate’ species), and the communication of these methods, has been relatively haphazard, often due to poor results and excessive mortality. Here, we provide a brief communication to describe a method to effectively transplant the stipitate kelp Ecklonia radiata—the most widespread and abundant kelp in Australasia—and which allowed the transplanting of >1,000 adult kelp over 1.5 ha. We also discuss additional observations relevant to the success of transplanting kelp (such as donor age/size), and the applicability of this method to other habitat‐forming macroalgae. Our method involved securing the adult Ecklonia to the substratum using large bands made from recycled rubber, which held the holdfast firmly but gently against the substratum. Re‐attachment of the adult kelp typically occurred within 3–6 weeks, while rates of survivorship were approximately 75% and not affected by the density nor size of the transplanted patch. This method could also readily be adapted to suit different substratum types and other species of kelp and habitat‐forming algae. Ultimately, this transplanting method adds to the collection of effective techniques for restoring habitat‐forming macroalgae, especially for stipitate species where few methods have been communicated.
Likelihood-Free Parameter Estimation for Dynamic Queueing Networks: Case Study of Passenger Flow in an International Airport Terminal
Authors: Ebert Anthony , Dutta Ritabrata , Mengersen Kerrie , Mira Antonietta , Ruggeri Fabrizio , Wu Paul
Published: April 2021

Dynamic queueing networks (DQN) model queueing systems where demand varies strongly with time, such as airport terminals. With rapidly rising global air passenger traffic placing increasing pressure on airport terminals, efficient allocation of resources is more important than ever. Parameter inference and quantification of uncertainty are key challenges for developing decision support tools. The DQN likelihood function is, in general, intractable and current approaches to simulation make likelihood-free parameter inference methods, such as approximate Bayesian computation (ABC), infeasible since simulating from these models is computationally expensive. By leveraging a recent advance in computationally efficient queueing simulation, we develop the first parameter inference approach for DQNs. We demonstrate our approach with data of passenger flows in a real airport terminal, and we show that our model accurately recreates the behaviour of the system and is useful for decision support. Special care must be taken in developing the distance for ABC since any useful output must vary with time. We use maximum mean discrepancy, a metric on probability measures, as the distance function for ABC. Prediction intervals of performance measures for decision support tools are easily constructed using draws from posterior samples, which we demonstrate with a scenario of a delayed flight.
On an averaged model for immiscible two‐phase flow with surface tension and dynamic contact angle in a thin strip
Authors: Lunowa Stephan B. , Bringedal Carina , Pop Iuliu Sorin
Published: April 2021

We consider a model for the flow of two immiscible fluids in a two‐dimensional thin strip of varying width. This represents an idealization of a pore in a porous medium. The interface separating the fluids forms a freely moving interface in contact with the wall and is driven by the fluid flow and surface tension. The contact‐line model incorporates Navier‐slip boundary conditions and a dynamic and possibly hysteretic contact angle law. We assume a scale separation between the typical width and the length of the thin strip. Based on asymptotic expansions, we derive effective models for the two‐phase flow. These models form a system of differential algebraic equations for the interface position and the total flux. The result is Darcy‐type equations for the flow, combined with a capillary pressure–saturation relationship involving dynamic effects. Finally, we provide some numerical examples to show the effect of a varying wall width, of the viscosity ratio, of the slip boundary condition as well as of having a dynamic contact angle law.
Low ferritin levels appear to be associated with worsened health in male repeat blood donors
Authors: Palokangas Elina , Lobier Muriel , Partanen Jukka , Castrén Johanna , Arvas Mikko
Published: April 2021

Background and objectives

Frequent blood donation depletes iron stores of blood donors. Iron depletion may lead to anaemia, but the health effects of iron depletion without anaemia in healthy blood donors are not well understood. We studied in the FinDonor cohort whether worsening of self‐rated health of blood donors during the study period was associated with biomarkers for iron levels or other self‐reported changes in lifestyle.

Materials and methods

We included 1416 participants from the cohort who answered an 89‐item questionnaire on their health and lifestyle during their enrolment visit and again at the end of the study. We performed multivariate logistic regression to test if blood donation‐related factors affected the probability of reporting worsened health. To set these findings into a more holistic context of health, we subsequently analysed all other questionnaire items with a data‐driven exploratory analysis.

Results

We found that donation frequency in men and post‐menopausal women and ferritin level only in men was associated negatively with worsened health between questionnaires. In the exploratory analysis, stable physical condition was the only questionnaire item that was associated negatively with worsened health in both women and men.

Conclusion

Our results suggest that low ferritin level is associated with worsened health even in non‐anaemic repeat donors, although we find that when health is analysed more holistically, ferritin and other factors primarily related to blood donation lose their importance.
Evaluation of a collaborator objective structured clinical examination (COSCE) in postgraduate medical education
Authors: Curran Vernon , Reid Adam , Coombs Heidi , Pike Pam , Farrell James , McPherson Ian , O'Dea Jennifer , Curtis Bryan , Trahey Julia
Published: April 2021

Background: Effective intra- and interprofessional collaboration abilities are necessary for safe and effective medical care, however such roles are often informally taught in postgraduate medical education with lack of opportunity for practice and feedback. The Objective Structured Clinical Encounter (OSCE) is a common approach in medical education. Adaptations of the OSCE have been found useful in the assessment of collaborator competencies amongst interprofessional student groups and assessment of intrinsic roles, like collaboration.Objective: The purpose of this study was to evaluate the effectiveness of a Collaborator Objective Structured Clinical Encounter (COSCE) as a method of formative assessment on collaborator competencies for postgraduate trainees. Methods: This study involved a one group, pretest-posttest evaluation conducted in 2018. PGY1 residents completed a Team Skills Scale immediately before and after COSCE participation, completed an evaluation survey to report satisfaction, and were assessed by facilitators and peer assessors using a COSCE rubric.Results: Residents reported significant improvement in their pre (N=35) to post-team skills (N=37) scores and an overall positive level of satisfaction with the COSCE experience (N=37/39, 94.9% response rate). Transfer of care skills (e.g., handover) demonstrated the lowest performance scores across all COSCE stations. Peer assessor (N = 204) and facilitator scores (N = 47) also indicated a moderate level of interrelatedness. Conclusion: A COSCE is a feasible method of formative assessment, fostering reflection and learning, and providing feedback on collaborator skills early in postgraduate medical education. Peer assessment may also hold promise as a formative assessment method on intra- and interprofessional collaboration.
Reflections on practice: A virally-infected curriculum must adapt or suffer!
Authors: Cobbold Christian , Wright Louise
Published: April 2021

Viruses are recognised for their ability to induce genetic evolution and cause disease. SARS-CoV-2 has catalysed rapid evolutionary changes in the delivery of preclinical teaching of the Griffith University medical program across diverse sites by inducing the use of progressive student feedback to enhance active learning in an online flipped format. These COVID-induced adaptations in medical education delivery, innovation and fast-tracked modernisation are, unlike viral infection, a curve that we embrace and do not want to squash.
Contextual prominence in vowel perception: Testing listener sensitivity to sonority expansion and hyperarticulation
Authors: Steffman Jeremy
Published: April 2021

High front vowels have been shown to undergo two competing forms of acoustic (and articulatory) modulation due to prosodic prominence—(1) hyperarticulation: more extreme high/front articulations under prominence and (2) sonority expansion: more open articulations, allowing more energy to radiate from the mouth. This study explores how these effects translate into listeners' perception of the contrast between the vowels /i/ and /ɪ/. Results show that listeners uniformly expect a hyperarticulated vowel (acoustically) under prominence, and adjust categorization of an F1/F2 continuum accordingly. Results are discussed in relation to production findings and possible accounts of why listeners favor hyperarticulation in perception.
Parity-preserving and magnetic field–resilient superconductivity in InSb nanowires with Sn shells
Authors: Pendharkar M. , Zhang B. , Wu H. , Zarassi A. , Zhang P. , Dempsey C. P. , Lee J. S. , Harrington S. D. , Badawy G. , Gazibegovic S. , Op het Veld R. L. M. , Rossi M. , Jung J. , Chen A.-H. , Verheijen M. A. , Hocevar M. , Bakkers E. P. A. M. , Palmstrøm C. J. , Frolov S. M.
Published: April 2021

Move aside, aluminum

Some of the most promising schemes for quantum information processing involve superconductors. In addition to the established superconducting qubits, topological qubits may one day be realized in semiconductor-superconductor heterostructures. The superconductor most widely used in this context is aluminum, in which processes that cause decoherence are suppressed. Pendharkar
et al.
go beyond this paradigm to show that superconducting tin can be used in place of aluminum (see the Perspective by Fatemi and Devoret). The authors grew nanowires of indium antimonide, which is a semiconductor, and coated them with a thin layer of tin without using cumbersome epitaxial growth techniques. This process creates a well-defined, “hard” superconducting gap in the nanowires, which is a prerequisite for using them as the basis for a potential topological qubit.

Science
, this issue p.
508
; see also p.
464
Decoupling transcription factor expression and activity enables dimmer switch gene regulation
Authors: Ricci-Tam C. , Ben-Zion I. , Wang J. , Palme J. , Li A. , Savir Y. , Springer M.
Published: April 2021

Circuit design for control of metabolism

A transcriptional control mechanism in yeast that allows cells to respond to changes in nutrient concentrations works very much like a household light-dimmer switch. That is, the system separately controls whether gene expression is “on” or “off” and the extent of gene expression. The galactose-responsive pathway is activated when yeast need to switch from metabolizing glucose to metabolizing galactose. Ricci-Tam
et al.
found that, rather than using two separate elements for the switch and dimmer controls, yeast use a single transcription factor, Gal4p, separately regulating its abundance (through transcriptional regulation) and its catalytic activity (through interaction with a protein-binding partner). Such regulation may be common and can allow responses to the environment on physiological and evolutionary time scales.

Science
, this issue p.
292
Materials challenges and opportunities for quantum computing hardware
Authors: de Leon Nathalie P. , Itoh Kohei M. , Kim Dohun , Mehta Karan K. , Northup Tracy E. , Paik Hanhee , Palmer B. S. , Samarth N. , Sangtawesin Sorawis , Steuerman D. W.
Published: April 2021

Combatting noise on the platform

The potential of quantum computers to solve problems that are intractable for classical computers has driven advances in hardware fabrication. In practice, the main challenge in realizing quantum computers is that general, many-particle quantum states are highly sensitive to noise, which inevitably causes errors in quantum algorithms. Some noise sources are inherent to the current materials platforms. de Leon
et al.
review some of the materials challenges for five platforms for quantum computers and propose directions for their solution.

Science
, this issue p.
eabb2823
Realization of an ideal Weyl semimetal band in a quantum gas with 3D spin-orbit coupling
Authors: Wang Zong-Yao , Cheng Xiang-Can , Wang Bao-Zong , Zhang Jin-Yi , Lu Yue-Hui , Yi Chang-Rui , Niu Sen , Deng Youjin , Liu Xiong-Jun , Chen Shuai , Pan Jian-Wei
Published: April 2021

A minimal Weyl semimetal

Many compounds have now been identified as Weyl semimetals, materials with an unusual electronic band structure characterized by the so-called Weyl points. Weyl points always appear in pairs, but the solid-state materials studied so far have at least four. Wang
et al.
engineered a Weyl semimetallic state with the minimum number of Weyl points (two) in a gas of ultracold atoms trapped in an optical lattice (see the Perspective by Goldman and Yefsah). To do that, the researchers had to create three-dimensional spin-orbit coupling in this system. The relative simplicity of the resulting band structure will make it easier to observe the unusual effects associated with this state.

Science
, this issue p.
271
; see also p.
234
Gapped magnetic ground state in quantum spin liquid candidate κ-(BEDT-TTF)
2
Cu
2
(CN)
3
Authors: Miksch Björn , Pustogow Andrej , Rahim Mojtaba Javaheri , Bardin Andrey A. , Kanoda Kazushi , Schlueter John A. , Hübner Ralph , Scheffler Marc , Dressel Martin
Published: April 2021

A gapped spin liquid

Quantum spin liquids avoid conventional magnetic ordering down to the lowest temperatures. Among the candidates for this state of matter, organic salts such as κ-(BEDT-TTF)
2
Cu
2
(CN)
3
have been prominent. Miksch
et al.
studied this material using electron spin resonance to elucidate the nature of its ground state. Instead of the expected gapless state, the temperature dependence of spin susceptibility suggests the formation of a spin gap.

Science
, this issue p.
276
Metagenomic analysis reveals global-scale patterns of ocean nutrient limitation
Authors: Ustick Lucas J. , Larkin Alyse A. , Garcia Catherine A. , Garcia Nathan S. , Brock Melissa L. , Lee Jenna A. , Wiseman Nicola A. , Moore J. Keith , Martiny Adam C.
Published: April 2021

Genomes reveal nutrient stress patterns

Within the surface ocean, nitrogen, iron, and phosphorous can all be limiting nutrients for phytoplankton depending on location. Ustick
et al.
used the prevalence of
Prochlorococcus
genes involved in nutrient acquisition to develop maps of inferred nutrient stress across the global ocean (see the Perspective by Coleman). They found broad patterns of limitation consistent with an Earth system model and nutrient addition experiments. Leveraging metagenomic data in this manner is an appealing approach that will help to expand our understanding of the biogeochemistry in the vast open ocean.

Science
, this issue p.
287
; see also p.
239