bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalent and incident anaemia in PARADIGM-HF and effect of sacubitril/valsartan
Authors: Curtain J , Adamson C , Jhund P S , Desai A S , Lefkowitz M P , Rizkala A R , Rouleau J L , Swedberg K , Zile M R , Solomon S D , Packer M , McMurray J J V
Published: October 2022

Background

Anaemia is common in patients with HFrEF and is associated with poor clinical outcomes. Although they reduce rates of mortality and heart failure hospitalization, renin-angiotensin (RAS) blockers lower haemoglobin and may induce anaemia. Concomitant neprilysin inhibition might ameliorate this effect of RAS blockers.

Purpose

We investigated the effect of sacubitril/valsartan compared with enalapril on clinical outcomes, according to anaemia status, and on haemoglobin levels in PARADIGM-HF.

Methods

Patient characteristics and clinical outcomes were compared between patients with and without anaemia (defined as haemoglobin <120 g/L in women and <130 g/L in men) at baseline. We investigated the effect of randomized treatment (sacubitril/valsartan or enalapril) on clinical outcomes according to anaemia status at screening. We also examined the effect of treatment on change in haemoglobin from baseline and on the incidence of anaemia. The primary endpoint in PARADIGM-HF was the composite of heart failure hospitalization or cardiovascular death.

Results

Of 8239 participants with a baseline haemoglobin measurement, 1677 (20.4%) were anaemic. Compared to those without anaemia, patients with anaemia had a more severe heart failure profile, worse kidney function, greater neurohormonal derangement and worse clinical outcomes. Sacubitril/valsartan, compared to enalapril, reduced the risk of the primary endpoint similarly in patients with anaemia (HR 0.84, 95% CI 0.71–1.00) and without anaemia (HR 0.78, 95% CI 0.71–0.87), p-value for interaction=0.478. Between baseline and 12 months, haemoglobin decreased by 1.5 (95% CI 1.7 to 1.2) g/L with sacubitril/valsartan compared with 2.3 (2.6 to 2.0) g/L with enalapril group: mean difference 0.8 (95% CI 0.5 to 1.2) g/L, p<0.001. The between-treatment difference apparent by 12 months, persisted up to 36 months. Patients assigned to sacubitril/valsartan were less likely to develop new anaemia at 12 months [321 of 2806 (11.4%)] compared to patients randomized to enalapril [440 of 2384 (15.6%)], odds ratio 0.70 (95% CI 0.60–0.81), p<0.001.

Conclusions

Compared to enalapril, sacubitril/valsartan reduced mortality and hospitalization in HFrEF patients with and without anaemia. Haemoglobin decreased less with sacubitril/valsartan and the incidence of new anaemia was lower in the sacubitril/valsartan group compared with the enalapril group.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): PARADIGM-HF was funded by Novartis.
Effects of sodium glucose cotransporter 2 inhibitors on the risk of hyperkalemia in patients on mineralocorticoid receptor antagonist: a systematic review and meta-analysis
Authors: Cordovez R A B , Denila R A , Rivera K , Patricio M
Published: October 2022

Background

Occurrence of hyperkalemia has been a great limitation in the full implementation of a guideline-directed medical therapy especially in patients with heart failure. Recent developments have exhibited the positive role of SGLT2 inhibitors, not only on the cardiovascular outcomes but also conferred renal protection.

Purpose

We explored the effects of SGLT2i and MRA combination on the risk of developing hyperkalemia.

Methods

Randomized controlled trials on SGLT2i versus placebo in patients already on MRA regardless of heart failure status reporting outcomes of potassium homeostasis were searched using Pubmed, CENTRAL, and ScienceDirect. Outcome of interest was the effects on the risk of hyperkalemia. Pooled hazard ratios with 95% confidence intervals were used as effect estimates using fixed-effects model.

Results

Four studies were included with a total of 8,996 patients. There was a significant reduction on the risk of hyperkalemia in the MRA with SGLT2i group (HR 0.53, 95% CI 0.39–0.73, p<0.0001) compared to MRA without SGLT2i group.

Conclusion

SGLT2i provides significant risk reduction on the development of hyperkalemia in patients already on a mineralocorticoid receptor antagonist.

Funding Acknowledgement

Type of funding sources: None.
Omecamtiv mecarbil for the management of heart failure: a meta-analysis of randomized controlled trials
Authors: Silva M M C A , Fernandes A , Hurtado V , Fernandes G , Cardoso R , Andersson C
Published: October 2022

Background

Omecamtiv mecarbil (OM) is a selective cardiac myosin activator that promotes contractility in patients with Heart Failure with Reduced Ejection Fraction (HFrEF). We aimed to study the clinical outcomes of OM in this population.

Methods

PubMed, Cochrane CENTRAL Registry of Controlled Trials, and ClinicalTrials.gov were searched for randomized controlled trials (RCTs) that compared OM with placebo for the management of HFrEF. Efficacy and safety data were summarized with odds ratios (OR) and a 95% confidence interval (CI) using a fixed-effect model predicting low heterogeneity between studies.

Results

Four RCTs were included, totalizing 9,364 patients, 4,779 treated with OM and 4,585 with placebo. Mean age ranged from 63–66 years, 15–22% female, ejection fraction 26–29%, ischemic etiology 53–66%. Length of follow up ranged from 1 to 21 months. There was no difference in the outcomes all cause death (OR 0.99, 95% CI 0.9–1.1, p=0.91), cardiovascular death (OR 1.01, 95% CI 0.91–1.12, p=0.87) and heart failure events or hospitalizations (OR 0.96, 95% CI 0.87–1.05, p=0.35), Figure.

Conclusion

In a meta-analysis of 4 RCTs, OM showed no difference compared with placebo in the risk of all-cause death, cardiovascular death, or heart failure events among patients with HFrEF.

Funding Acknowledgement

Type of funding sources: None.
Predictors of long-term prognosis based on measurements achieved after 9-week hybrid telerehabilitation in heart failure patients – a subanalyis of the TELEREH-HF RCT
Authors: Piotrowicz E , Pencina M , Kowalik I , Orzechowski P , Banach M , Glowczynska R , Zareba W , Opolski G , Szalewska D , Pluta S , Kalarus Z , Irzmanski R , Piotrowicz R
Published: October 2022

Background

Predicting prognosis in heart failure (HF) is of major importance.

The purpose of the study was to define predictors influencing long-term cardiovascular mortality or HF hospitalization (“composite outcome”) based on clinical status and measurements obtained after the 9-week hybrid comprehensive telerehabilitation (HCTR) programme.

Methods

This analysis is based on TELEREH-HF multicenter, randomized trial that enrolled 850 HF patients (NYHA I-III; left ventricular ejection fraction [LVEF]≤40%). Patients were randomized 1:1 to 9-week HCTR plus usual care (development sample) or usual care only (validation sample) and followed for 12–24 months for development of the composite.

Results

The predictors of our composite were: non-ischaemic etiology of HF, diabetes, higher serum level of: N-terminal prohormone of brain natriuretic peptide, creatinine, and high-sensitivity C-Reactive Protein; low carbon dioxide output at peak exercise, high minute ventilation and breathing frequency at maximum effort in cardiopulmonary test; increase of delta of average heart rate in 24h-ECG Holter monitoring, lower LVEF and patients' non-adherence to HCTR. The model discrimination C-index=0.795 and decreased to 0.755 on validation (Table 1). The 2-year risk of the composite was 48% in the top tertile versus 5% in the bottom tertile (Figure 1).

Conclusion

Risk factors collected at the end of the 9-week telerehabilitaion period did an excellent job in stratifying patients based on their 2-year risk of the composite outcome. Patients in the top tertile had an almost ten-fold higher risk compared to patients in the bottom tertile. Adherence to treatment but not peakVO2 or quality of life were significantly associated with the outcome.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Centre for Research and Development, Warsaw, Poland
Evaluating systemic immune-inflammation index in patients with implantable cardioverter defibrillator for heart failure with reduced ejection fraction
Authors: Hayiroglu M , Cinar T , Cinier G , Pay L , Yumurtas A C , Tezen O , Eren S , Kolak Z , Cetin T , Cicek V , Tekkesin A I
Published: October 2022

Background

Pro-inflammatory pathways play a serious role in the follow-up of patients with intracardiac defibrillator (ICD) for heart failure reduced with ejection fraction (HFrEF). A newly defined index, which is named as systemic immune-inflammation index (SII), has been recently reported to have prognostic value in patients with cardiovascular disease.

Purpose

The aim of this investigation is to evaluate the value of SII in terms of its association with long-term mortality and appropriate ICD therapy during in 10-year follow-up.

Methods

This retrospective study included 1011 patients with ICD for HFrEF. The study population was divided into two groups according to optimal cut-off value of SII to predict long-term mortality. The long-term prognostic impact of SII on these patients were evaluated in terms of mortality and appropriate ICD therapy.

Results

A receiver operating characteristic curve analyses of systemic immune-inflammation index, platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio in long-term mortality and appropriate intracardiac defibrillator therapy for patients intracardiac defibrillator for heart failure reduced with ejection fraction were presented in Figure 1A and 1B respectively. The patients with higher SII had significantly higher long-term mortality and appropriate ICD therapy. After adjustment for all confounding factors, the long-term mortality had 5.1 higher rates at higher SII. (95% CI: 2.9–8.1). The long-term appropriate ICD therapy also had 2.0 higher rates at higher SII (95% CI: 1.4–3.0). Kaplan Meier survival analysis of patients according to the systemic immune-inflammation index was presented in Figure 2.

Conclusion

SII, calculated using neutrophil, platelet, and lymphocyte counts, may be an independent predictive marker for both long-term mortality and appropriate ICD therapy in patients with HFrEF.

Funding Acknowledgement

Type of funding sources: None.
Diabetes may modify the efficacy of primary prevention implantable cardioverter-defibrillators in non-ischemic systolic heart failure: an extended follow-up of the DANISH trial
Authors: N Doi S , Butt J H , Rorth R , Thune J J , Nielsen J C , Haarbo J , Eiskjaer H , Hassager C , Svendsen J H , Hofsten D E , Torp-Pedersen C , Pehrson S , Kristensen S L , Kober L
Published: October 2022

Background

Since patients with both diabetes and heart failure (HF) have a substantially worse prognosis than those with each of these alone, the efficacy of implantable cardioverter defibrillator (ICD) implantation in patients with systolic HF may be modified by diabetes status.

Purpose

In this extended follow-up analysis of the Danish Study to Assess the Efficacy of primary prevention of Implantable Cardioverter Defibrillators in Patients with Non-ischemic Systolic Heart failure on Mortality (DANISH), adding four years of additional follow-up, we examined the long-term effects of primary prophylactic ICD implantation, compared with usual clinical care, in patients with non-ischemic systolic HF according to diabetes status.

Methods

In DANISH, 1,116 patients with non-ischemic systolic HF were randomized to receive an ICD (N=556) or usual clinical care (N=550). Outcomes were analyzed according to diabetes status at baseline. The primary outcome was death from any cause. Secondary outcomes were cardiovascular death and sudden cardiovascular death.

Results

Of the 1,116 patients randomized in DANISH, 211 (18.9%) had diabetes at baseline (median age 64 year-old, 159 males, median left ventricular ejection fraction 25%). There was a statistically significant interaction between diabetes and the effect of ICD implantation on death from any cause and cardiovascular death. There was a trend toward a reduction in both outcomes with ICD implantation, compared with usual clinical care; in patients without diabetes (death from any cause, HR 0.81 [95% CI, 0.65–1.01]; cardiovascular death, HR 0.77 [0.59–1.01]), but not in those with diabetes (death from any cause, HR 1.19 [0.81–1.74]; cardiovascular death, HR 1.20 [0.79–1.82]) (P for interaction = 0.04 and 0.04 for death from any cause and cardiovascular death, respectively). Although there was no statistically significant interaction between diabetes and the effect of ICD implantation on sudden cardiovascular death, ICD implantation significantly reduced the rate of sudden cardiovascular death in patients without diabetes (HR 0.51 [0.31–0.85]), but not in those with diabetes (HR 0.91 [0.41–1.99]) (P for interaction = 0.15).

Conclusions

In patients with non-ischemic systolic HF, there was a significant interaction between diabetes and the effect of ICD implantation on death from any cause and cardiovascular death, suggesting that individuals without diabetes may derive greater benefit from ICD implantation.

Funding Acknowledgement

Type of funding sources: None.
Fusion CRT pacing: septal flash significance in super responder patients
Authors: Vacarescu C , Luca C T , Gaita D , Crisan S , Mornos C , Goanta E V , Lazar M A , Ionac I , Arnautu D A , Cozma D
Published: October 2022

Background

LV only CRT pacing is an option that may be considered to maximize response to CRT and at least as an alternative in non-responders to biventricular (BiV) pacing. However, criteria to best titrate therapy on an individual basis are lacking in fusion pacing. On the other hand, septal flash (SF) is a strong predictor of favorable response for patients (pts) with BiV pacing.

Purpose

To analyze the relationship between SF and the response to fusion CRT pacing.

Methods

Consecutive pts with exclusive fusion CRT-P were included. Right atrium/left ventricle leads DDD CRT pacing system were used in all patients. Prospective data were collected at every 6 months follow-up visits: device interrogation, exercise test, echocardiographic parameters. Exercise tests, device reprogramming and medication optimization were performed regular in order to maximize CRT response. Patients were divided in 2 groups: super-responders (SR) and responders (R). SRs were defined those with left ventricular end-systolic volume (LVESV) improvement ≥30% and stable ejection fraction (LVEF) ≥45%.

Results

69 pts with NYHA II–III heart failure and non-ischemic dilated cardiomyopathy were initially included. 5 pts were non responders and excluded (non LBBB, spontaneous QRS <149 ms). Final analyzed group had 64 pts (35 male) aged 60±12 y.o. The mean follow-up was 54±19 months; 22 pts (34%) were SRs. At baseline, SF was found in all SR pts and in 55% of R pts. SF was corrected post CRT in all patients, except one. For this patient (LV lead in a posterior branch of the coronary sinus – CS) the strategy included an upgrade to triple chamber device with a second lead in a lateral branch of the CS and became SR from R. Mitral regurgitation decreased in 38 patients (all SR, 40% R). Interesting, baseline left atrium volume and pulmonary sistolic artery pressure were smaller in SR versus R group, however SF did not corelate with LA volume/diastolic dysfunction.

Conclusions

Septal flash seems to be a strong predictor of super-response in patients with fusion CRT pacing. This finding could improve the selection of candidates for fusion CRT-P, however larger studies are needed to assess SF in this categories of patients.

Funding Acknowledgement

Type of funding sources: None.
Expansion and Neofunctionalization of Actinoporin-like Genes in Mediterranean Mussel (Mytilus galloprovincialis)
Authors: Koritnik Neža , Gerdol Marco , Šolinc Gašper , Švigelj Tomaž , Caserman Simon , Merzel Franci , Holden Ellie , Benesch Justin L P , Trenti Francesco , Guella Graziano , Pallavicini Alberto , Modica Maria Vittoria , Podobnik Marjetka , Anderluh Gregor
Published: October 2022

Pore-forming toxins are an important component of the venom of many animals. Actinoporins are potent cytolysins that were first detected in the venom of sea anemones; however, they are occasionally found in animals other than cnidarians and are expanded in a few predatory gastropods. Here, we report the presence of 27 unique actinoporin-like genes with monophyletic origin in Mytilus galloprovincialis, which we have termed mytiporins. These mytiporins exhibited a remarkable level of molecular diversity and gene presence–absence variation, which warranted further studies aimed at elucidating their functional role. We structurally and functionally characterized mytiporin-1 and found significant differences from the archetypal actinoporin fragaceatoxin C. Mytiporin-1 showed weaker permeabilization activity, no specificity towards sphingomyelin, and weak activity in model lipid systems with negatively charged lipids. In contrast to fragaceatoxin C, which forms octameric pores, functional mytiporin-1 pores on negatively charged lipid membranes were hexameric. Similar hexameric pores were observed for coluporin-26 from Cumia reticulata and a conoporin from Conus andremenezi. This indicates that also other molluscan actinoporin-like proteins differ from fragaceatoxin C. Although the functional role of mytiporins in the context of molluscan physiology remains to be elucidated, the lineage-specific gene family expansion event that characterizes mytiporins indicates that strong selective forces acted on their molecular diversification. Given the tissue distribution of mytiporins, this process may have broadened the taxonomic breadth of their biological targets, which would have important implications for digestive processes or mucosal immunity.
Explicit criteria for exponential stability in mean square of stochastic difference systems with delays
Authors: Trung Hieu Le , Huu anh Ngoc Pham , Bao Tran Thai , Dinh Huy Nguyen
Published: October 2022

By a novel approach, we present some new criteria for the exponential stability in mean square of solutions of non-linear stochastic difference systems with time-varying delays. A discussion of the obtained results is given. Illustrative examples and simulations are provided.
Multilevel quasi-interpolation
Authors: Franz Tino , Wendland Holger
Published: October 2022

Quasi-interpolation methods are well-established tools in multivariate approximation. They are efficient as they do not require, in contrast to interpolation, the solution of a linear system. Quasi-interpolations are often first studied on infinite grids. Here, it is usually required that the quasi-interpolation operator reproduces polynomials of a certain degree exactly. This degree corresponds to the approximation order of the quasi-interpolation process. Unfortunately, if a radial, compactly supported kernel is employed for building the quasi-interpolation operator, it is well known that polynomial reproduction is impossible in two or more dimensions. As such operators are numerically appealing and are frequently used in particle methods, we will, in this paper, look at such quasi-interpolation operators that do not reproduce polynomials and show that they lead, when employed in a multilevel scheme, to an efficient and converging approximation method.
The Cost of Resistance to Diamide Insecticide Varies With the Host Plant in Spodoptera frugiperda (Lepidoptera: Noctuidae)
Authors: Oliveira Padovez Fernando Elias , Hideo Kanno Rubens , Zaia Zambon Gustavo , Omoto Celso , Sartori Guidolin Aline
Published: October 2022

Fitness costs associated with insect resistance to insecticides can be exploited to implement resistance management programs. However, most of these studies are restricted to evaluating biological traits on artificial diets. Here, we investigated the fitness cost associated with chlorantraniliprole in Spodoptera frugiperda (J.E. Smith) feeding on corn, soybean, and cotton plants. We used a near-isogenic strain of S. frugiperda resistant to chlorantraniliprole (Iso-RR), a susceptible strain (SS), and heterozygotes strains (H1 and H2) to evaluate several biological and population growth parameters. Larval survival of the Iso-RR strain was on average 90% on corn, 65% on soybean, and 57% on cotton plants. Development time of the larval stage also differed among host plants, Iso-RR strain took on average 14, 17, and 26 days to reach the pupal stage on corn, soybean, and cotton plants respectively. Net reproductive rate, intrinsic rate of population increase, and finite rate of population increase were higher for Iso-RR strain feeding on corn plants than other host plants. The relative fitness, based on the intrinsic rate of population increase, of S. frugiperda resistant strain on corn, soybean, and cotton plants were 1.04, 0.85, and 0.88, respectively. Therefore, no fitness cost was observed for S. frugiperda feeding on corn plants, but a significant fitness cost was observed when this pest fed on soybean and cotton plants. We showed that the food source influences the fitness cost of S. frugiperda resistant to diamide. Such information may help to implement resistance management strategies based on each crop.
Schumpeter Lecture 2022: Job Search in the 21St Century
Authors: Kircher Philipp
Published: October 2022

Formal job search has undergone massive transformations in the last two decades with the move to online platforms. This makes more stages of the job search process observable, and allows researchers to intervene in this market and improve the design of the job search process and the information available in it. This paper showcases studies that illustrate the potential of analyzing online job search data and of intervening in the online job search process. It presents the current insights and some open questions and highlights conditions under which some of the recent interventions are likely to improve market outcomes overall, rather than improving only the outcomes for the treated individuals.
Genocide and Ukraine
Authors: Schabas William A
Published: October 2022

Allegations of genocide have been made on both sides during the armed conflict in Ukraine. This article reviews the claims, concluding that they appear to be inconsistent with the crime of genocide as defined in Article II of the 1948 Convention, as interpreted by the International Court of Justice, the ad hoc tribunals and the International Law Commission. Most of the claims appear to use the term genocide in a rhetorical sense, without serious concern for the legal issues. The available evidence does not permit inferences to be drawn that the punishable acts are committed with genocidal intent, to the exclusion of other reasonable explanations.
From West to East: Mercosur and Singapore agree on FTA
Authors: Carls Suelen , Amal Mohamed
Published: October 2022

Among the Mercosur countries (Argentina, Brazil, Paraguay and Uruguay), the free trade agreement between them and Singapore reveals Brazil’s clear interest in expanding economic and trade relations with key players in Asia, a highly dynamic trading area.
What Is the Appropriate Dose, Route, and Duration of Antibiotic Therapy for Pediatric Acute Hematogenous Osteomyelitis (AHO)? I Wish I Knew
Authors: Bradley John S
Published: October 2022

Treatment of pediatric AHO requires antibiotic/surgical management. Considerable clinical experience exists, but with current knowledge of antibiotic pharmacokinetics and pharmacodynamics, recommendations for dosages for old or new antibiotics should be based on current standards for drug development whenever possible.
Differential Effects on HbA1c Detection by HPLC and Capillary Electrophoresis in Five Types of Hb Variants in China
Authors: Wei Luo , Weifeng Zhang , Zuoliang Dong
Published: October 2022

Objective

Hemoglobin A1c (HbA1c) can be used to evaluate blood glucose control. Its measurement will be affected by many factors, but Hb variation is the most critical factor. This study aimed to explore the types of variants found in routine work and their impact on test results.

Methods

Samples with abnormal HbA1c chromatograms found in routine testing were tested with high-performance liquid chromatography (HPLC) and capillary electrophoresis (CE) and then further tested with polymerase chain reaction (PCR) and sequencing.

Results

Five recessive heterozygous mutations were identified after PCR and sequencing. Hb Riccarton-II (a mutation in the HBA2 gene), Hb E, Hb G-Coushatta, Hb G-Taipei, and Hb North Manchester (a mutation in the HbB gene) were identified. All HbA1c values of these variants detected by HLC-723 G8 (HPLC method) were lower than those of Sebia Capillarys 2 FP (C2FP, CE method) with P < .0001.

Conclusion

Five Hb mutations were identified in our routine HbA1c test, and their HPLC detection values were significantly lower than those obtained with the CE method.
A Decade of Surgery Aboard the U.S. Naval Ship COMFORT (T-AH 20)
Authors: Worlton Tamara J , Gunasingha Rathnayaka M K D , Atwood Rex , Johnson Mark , Uber Ian C
Published: October 2022

Introduction

The U.S. Naval Ship COMFORT has performed six humanitarian assistance and disaster relief mission since 2007. This paper describes the surgical volume per surgical specialty for five missions spanning 19 countries.

Materials and Methods

Raw surgical case logs were analyzed for total case volume, total operating days, unanticipated return to operating room, and percentage of pediatric cases (<18 years old) for each country visited.

Results

Total surgical volume for the five missions was 5,142. The countries most frequently visited were Columbia and Haiti with seven and five visits, respectively. General surgery, ophthalmology, and plastic surgery have had consistent volume over time. Orthopedic surgery volume has steadily decreased with the exception of the 2018 mission.

Conclusion

As volume in military treatment facilities declines, alternative sources of surgical volume for military surgeons are being examined. This paper highlights the historical volume which can inform future personnel planning requirements of U.S. Naval Ship COMFORT missions. With the exception of orthopedic surgery, surgical volume has remained consistent over the last decade. For future best practice, historical case data should be used to determine staffing needs on hospital ships and case logs and operating procedures and follow-up protocols should be standardized.
Self-Reported Health Care Avoidance Behavior in U.S. Military Pilots Related to Fear for Loss of Flying Status
Authors: Hoffman William R , Aden James K , Barbera Daniel , Tvaryanas Anthony
Published: October 2022

Introduction

U.S. military pilots are required to meet certain medical standards in order to maintain an active flying status. Military pilots face potential temporary or permanent loss of flying privileges in the setting of a new condition or symptom that does not meet required standards, which could result in negative social and occupational repercussions for the pilot. For this reason, it has been proposed that U.S. military pilots participate in health care avoidance behavior, but little evidence exists to characterize such a trend in this population.

Materials and Methods

We conducted a non-probabilistic Internet survey of the general population of U.S. pilots from November 1, 2019 through August 1, 2021. The current study is a sub-analysis of military pilots.

Results

A total of 4,320 pilots answered the informed consent question, and 264 selected one military pilot type and were included in this sub-analysis. There were 72% of military pilots who reported a history of health care avoidance behavior (n = 190), and no statistical difference was found between age groups, gender, and military pilot types. There were 55.5% of pilots who reported a history of seeking informal medical care (n = 147), 33.7% of pilots who have flown despite a new symptom they felt required medical evaluation, 42.5% of pilots who reported withholding information on aeromedical screening (n = 111), and 11.4% of pilots who reported a history of undisclosed prescription medication use (n = 30).

Conclusions

U.S. military pilots may participate in health care avoidance behavior because of fear for loss of flying status.
Do post-starburst galaxies host compact molecular gas reservoirs?
Authors: Sun Fengwu , Egami Eiichi
Published: October 2022

We analysed the high-resolution (up to ∼0.2 arcsec) ALMA CO (2–1) and 1.3 mm dust continuum data of eight gas-rich post-starburst galaxies (PSBs) in the local Universe, six of which had been studied by a recent work. In contrast to this study reporting the detections of extraordinarily compact (i.e. unresolved) reservoirs of molecular gas in the six PSBs, our visibility-plane analysis resolves the CO (2–1) emission in all eight PSBs with effective radii (Re, CO) of $0.8_{-0.4}^{+0.9}$ kpc, typically consisting of gaseous components at both circumnuclear and extended disc scales. With this new analysis, we find that the CO sizes of gas-rich PSBs are compact with respect to their stellar sizes (median ratio $=0.43_{-0.21}^{+0.27}$), but comparable to the sizes of the gas discs seen in local luminous infrared galaxies (LIRGs) and early-type galaxies. We also find that the CO-to-stellar size ratio of gas-rich PSBs is potentially correlated with the gas depletion time-scale, placing them as transitional objects between LIRGs and early-type galaxies from an evolutionary perspective. Finally, the star formation efficiency of the observed PSBs appear consistent with those of star-forming galaxies on the Kennicutt–Schmidt relation, showing no sign of suppressed star formation from turbulent heating.
Biochemical studies highlight determinants for metal selectivity in the Escherichia coli periplasmic solute binding protein NikA
Authors: Law Wayne W H , Kanelis Voula , Zamble Deborah B
Published: October 2022

Nickel is an essential micronutrient for the survival of many microbes. On account of the toxicity of nickel and its scarcity in the environment, microbes have evolved specific systems for uptaking and delivering nickel to enzymes. NikA, the solute binding protein for the ATP-binding cassette (ABC) importer NikABCDE, plays a vital role in the nickel homeostasis of Escherichia coli by selectively binding nickel over other metals in the metabolically complex periplasm. While the endogenous ligand for NikA is known to be the Ni(II)–(L-His)2 complex, the molecular basis by which NikA selectively binds Ni(II)–(L-His)2 is unclear, especially considering that NikA can bind multiple metal-based ligands with comparable affinity. Here we show that, regardless of its promiscuous binding activity, NikA preferentially interacts with Ni(II)–(L-His)2, even over other metal–amino acid ligands with an identical coordination geometry for the metal. Replacing both the Ni(II) and the L-His residues in Ni(II)–(L-His)2 compromises binding of the ligand to NikA, in part because these alterations affect the degree by which NikA closes around the ligand. Replacing H416, the only NikA residue that ligates the Ni(II), with other potential metal-coordinating amino acids decreases the binding affinity of NikA for Ni(II)–(L-His)2 and compromises uptake of Ni(II) into E. coli cells, likely due to altered metal selectivity of the NikA mutants. Together, the biochemical and in vivo studies presented here define key aspects of how NikA selects for Ni(II)–(L-His)2 over other metal complexes, and can be used as a reference for studies into the metal selectivity of other microbial solute binding proteins.
Confidence at the limits of human nested cognition
Authors: Recht Samuel , Jovanovic Ljubica , Mamassian Pascal , Balsdon Tarryn
Published: October 2022

Metacognition is the ability to weigh the quality of our own cognition, such as the confidence that our perceptual decisions are correct. Here we ask whether metacognitive performance can itself be evaluated or else metacognition is the ultimate reflective human faculty. Building upon a classic visual perception task, we show that human observers are able to produce nested, above-chance judgements on the quality of their decisions at least up to the fourth order (i.e. meta-meta-meta-cognition). A computational model can account for this nested cognitive ability if evidence has a high-resolution representation, and if there are two kinds of noise, including recursive evidence degradation. The existence of fourth-order sensitivity suggests that the neural mechanisms responsible for second-order metacognition can be flexibly generalized to evaluate any cognitive process, including metacognitive evaluations themselves. We define the theoretical and practical limits of nested cognition and discuss how this approach paves the way for a better understanding of human self-regulation.
Space-frequency-polarization-division multiplexed wireless communication system using anisotropic space-time-coding digital metasurface
Authors: Ke Jun Chen , Chen Xiangyu , Tang Wankai , Chen Ming Zheng , Zhang Lei , Wang Li , Dai Jun Yan , Yang Jin , Zhang Jun Wei , Wu Lijie , Cheng Qiang , Jin Shi , Cui Tie Jun
Published: October 2022

In the past few years, wireless communications based on digital coding metasurfaces have gained research interest owing to their simplified architectures and low cost. However, in most of the metasurface-based wireless systems, a single-polarization scenario is used, limiting the channel capacities. To solve the problem, multiplexing methods have been adopted, but the system complexity is inevitably increased. Here, a space-frequency-polarization-division multiplexed wireless communication system is proposed using an anisotropic space-time-coding digital metasurface. By separately designing time-varying control voltage sequences for differently oriented varactor diodes integrated on the metasurface, we achieve frequency-polarization-division multiplexed modulations. By further introducing different time-delay gradients to the control voltage sequences in two polarization directions, we successfully obtain space-frequency-polarization-division multiplexed modulations to realize a wireless communication system with a new architecture. The new communication system is designed with compact dual-polarized meta-elements, and can improve channel capacity and space utilization. Experimental results demonstrate the high-performance and real-time transmission capability of the proposed communication system, confirming its potential application in multiple-user collaborative wireless communications.
Smoking Behaviors Among Indigenous Pregnant People Compared to a Matched Regional Cohort
Authors: Rusk Ann M , Giblon Rachel E , Chamberlain Alanna M , Patten Christi A , Felzer Jamie R , Bui Yvonne T , Wi Chung-Il. , Destephano Christopher C , Abbott Barbara A , Kennedy Cassie C
Published: October 2022

Introduction

Smoking commercial tobacco products is highly prevalent in American Indian and Alaska Native (Indigenous) pregnancies. This disparity directly contributes to maternal and fetal mortality. Our objective was to describe cigarette smoking prevalence, cessation intervention uptake, and cessation behaviors of pregnant Indigenous people compared to sex and age-matched regional cohort.

Aims and Methods

Pregnancies from an Indigenous cohort in Olmsted County, Minnesota, identified in the Rochester Epidemiology Project, were compared to pregnancies identified in a sex and age-matched non-Indigenous cohort from 2006 to 2019. Smoking status was defined as current, former, or never. All pregnancies were reviewed to identify cessation interventions and cessation events. The primary outcome was smoking prevalence during pregnancy, with secondary outcomes measuring uptake of smoking cessation interventions and cessation.

Results

The Indigenous cohort included 57 people with 81 pregnancies, compared to 226 non-Indigenous people with 358 pregnancies. Smoking was identified during 45.7% of Indigenous pregnancies versus 11.2% of non-Indigenous pregnancies (RR: 3.25, 95% CI = 1.98–5.31, p ≤ .0001). Although there was no difference in uptake of cessation interventions between cohorts, smoking cessation was significantly less likely during Indigenous pregnancies compared to non-Indigenous pregnancies (OR: 0.23, 95% CI = 0.07–0.72, p = .012).

Conclusions

Indigenous pregnant people in Olmsted County, Minnesota were more than three times as likely to smoke cigarettes during pregnancy compared to the non-indigenous cohort. Despite equivalent uptake of cessation interventions, Indigenous people were less likely to quit than non-Indigenous people. Understanding why conventional smoking cessation interventions were ineffective at promoting cessation during pregnancy among Indigenous women warrants further study.

Implications

Indigenous pregnant people in Olmsted County, Minnesota, were greater than three times more likely to smoke during pregnancy compared to a regional age matched non-Indigenous cohort. Although Indigenous and non-Indigenous pregnant people had equivalent uptake of cessation interventions offered during pregnancy, Indigenous people were significantly less likely to quit smoking before fetal delivery. This disparity in the effectiveness of standard of care interventions highlights the need for further study to understand barriers to cessation in pregnant Indigenous people.
Citrullinated and carbamylated proteins in extracellular microvesicles from plasma of patients with rheumatoid arthritis
Authors: Ucci Federica M , Recalchi Serena , Barbati Cristiana , Manganelli Valeria , Capozzi Antonella , Riitano Gloria , Buoncuore Giorgia , Garofalo Tina , Ceccarelli Fulvia , Spinelli Francesca R , Balbinot Eugenia , Celia Alessandra Ida , Longo Agostina , Alessandri Cristiano , Misasi Roberta , Sorice Maurizio , Conti Fabrizio
Published: October 2022

Objectives

To investigate the expression of citrullinated and carbamylated proteins in extracellular microvesicles (EMVs) from RA patients.

Methods

We enrolled 24 RA naïve for biological therapy and 20 healthy donors (HD), matched for age and sex. For each patient, laboratory and clinical data were recorded and clinical indexes were measured (Clinical Disease Activity Index, Simplified Disease Activity Index, DAS28). EMVs in RA patients and HD were purified from plasma and measured by nanoparticle tracking analysis (NanoSight). Further, EMVs were incubated with anti-citrullinated/carbamylated proteins antibodies and processed by flow cytometry and western blot to evaluate the expression of citrullinated/carbamylated antigens.

Results

NanoSight revealed a significant increase of EMVs in RA compared with HD. Moreover, cytofluorimetric analysis showed a significative higher expression of citrullinated antigens on EMVs’ surface in RA than donors, while no substantial difference was found in the expression of carbamylated antigens. These data were confirmed by western blot which identified vimentin, glycolytic enzyme alpha-enolase 1 and collagen type II as the main citrullinated and carbamylated proteins carried by EMVs. Finally, a relevant correlation between the expression of citrullinated antigens and disease activity was found.

Conclusions

The results of this study suggest an involvement of EMVs in the pathogenesis of RA by inducing autoimmunity.
Compressibility analysis as robust in-die compression analysis for describing tableting behaviour
Authors: Berkenkemper Sabrina , Kleinebudde Peter
Published: October 2022

Objectives

Compressibility of materials is determining the tableting behaviour and tablet properties during and after manufacturing. The compressibility constant has not been investigated as an in-die method yet and was therefore compared with the Heckel analysis for describing the compressibility of materials during tableting in the present study.

Methods

Various parameters influencing tableting, such as compression pressure, compression speed and punch diameter, were used to analyse the robustness of both methods and to evaluate the informative value of the compression parameters. Twelve common pharmaceutical excipients were used to cover a wide range of material properties.

Key findings

The compressibility constant was successfully applied as an in-die method and proved to be more robust against the influencing parameters during tableting than the Heckel analysis. A good correlation between the out-of-die and in-die method was found for both methods but could not be observed between the compressibility constant and the yield pressure from Heckel analysis. The methods are both describing the volume reduction of materials under pressure but focus on different material properties.

Conclusions

For material characterisation in the field of tableting, the compressibility constant can be additionally applied in the future to be able to determine another compressibility parameter in combination with the yield pressure.
The effects of administering different metaphylactic antimicrobials on growth performance and health outcomes of high-risk, newly received feedlot steers
Authors: Coppin Carley M , Smock Taylor M , Helmuth Cory L , Manahan Jeff L , Long Nathan S , Hoffman Ashley A , Carroll Jeffrey A , Broadway Paul R , Burdick Sanchez Nicole C , Wells James E , Fernando Samodha C , Hales Kristin E
Published: October 2022

Bovine respiratory disease (BRD) is the primary animal health concern facing feedlot producers. Many antimicrobial mitigation strategies are available, but few studies have compared feedlot performance during both the receiving and finishing periods following application of different antimicrobials used as metaphylaxis at arrival. The objective of this study was to compare antimicrobial metaphylaxis methods on clinical health and growth performance across both the receiving and finishing periods. A total of 238 multiple-sourced steers in two source blocks were used in a generalized complete block design. The four treatments included: 1) a negative control, 5 mL of sterile saline injected subcutaneously (CON); 2) subcutaneous administration of florfenicol at 40 mg/kg of BW (NUF); 3) subcutaneous administration of ceftiofur in the posterior aspect of the ear at 6.6 mg/kg of BW (EXC); and 4) subcutaneous administration of tulathromycin at 2.5 mg/kg of BW (DRA). The morbidity rate for the first treatment of BRD was decreased for the DRA and EXC treatments compared to CON and NUF (P < 0.01). Additionally, average daily gain (ADG), dry matter intake (DMI), and gain-to-feed (G:F) were greater (P ≤ 0.02) in the DRA treatment during the receiving period compared to all other treatments. The ADG was also greater (P < 0.05) for EXC than the CON treatment throughout the finishing period. Nonetheless, other growth performance variables did not differ among metaphylactic treatments during the finishing period (P ≥ 0.14). Likewise, no differences in carcass characteristics or liver abscess score were observed (P ≥ 0.18). All complete blood count (CBC) variables were affected by day (P ≤ 0.01) except mean corpuscular hemoglobin concentration (P = 0.29). Treatment × time interactions were observed for platelet count, white blood cell (WBC) count, monocyte count and percentage, and lymphocyte percentage (P ≤ 0.03). However, there were no observed hematological variables that differed among treatment (P ≥ 0.10). The results indicate that some commercially available antimicrobials labeled for metaphylactic use are more efficacious than others in decreasing morbidity rate.
Effects of Temperature and Moisture Duration on Spore Germination of Four Fungi that Cause Grapevine Trunk Diseases
Authors: Ji Tao , Altieri Valeria , Salotti Irene , Rossi Vittorio
Published: October 2022

Grapevine trunk diseases (GTDs) are serious threats worldwide and are difficult to control, in part because the environmental requirements for epidemiological processes of the causal fungi are poorly understood. Therefore, we investigated the effects of temperature and moisture duration on spore germination of four fungi associated with two GTDs (esca complex and Eutypa dieback): Phaeomoniella chlamydospora, Phaeoacremonium minimum, Cadophora luteo-olivacea, and Eutypa lata. Conidia of Phaeomoniella chlamydospora, Phaeoacremonium minimum, and C. luteo-olivacea were similar: conidia of these fungi germinated profusely (>90%) between 20 and 30°C; Phaeomoniella chlamydospora and Phaeoacremonium minimum tended to germinate at higher temperatures (up to 40°C for P. minimum), and C. luteo-olivacea at lower temperatures (as low as 5°C). E. lata ascospores germinated between 10 and 30°C. The required duration of moist periods for germination was shortest for C. luteo-olivacea (about 6 h), followed by P. minimum and E. lata (about 12 h) and Phaeomoniella chlamydospora (about 24 h). Further research on the environmental requirements of GTD fungi may increase our ability to predict infection periods and, thereby, improve disease control.
Diseases Involving the Specialized Folds of the Peritoneum: The Omentum and Mesentery
Authors: Chung Katherine , Krumenacker Kristin , Ros Pablo R.
Published: October 2022

Primary diseases involving the mesentery and omentum are rare and thus easily overlooked. Due to their proximity to the abdominal and pelvic organs, the mesentery and omentum are often victims of inflammation, edema, hemorrhage, and neoplasms. Furthermore, these diseases often have nonspecific and overlapping imaging features, posing a diagnostic challenge to radiologists and necessitating reliance on clinical information. The terms “peritoneum,” “mesentery,” and “omentum” are often used interchangeably, although these structures are not the same. Effective treatment relies on both diagnostic and anatomical accuracy. The goal of this article is to define the peritoneum and its specialized folds and then review a gamut of diseases involving the mesentery and omentum.
What Is the Safe Window from Definitive Fixation to Flap Coverage in Type 3B Open Tibia Fractures? Supporting Plastics and Orthopaedics Alliance in Reducing Trauma Adverse Events (SPARTA)
Authors: Al-Hourani Khalid , Foote Clary J. , Duckworth Andrew D. , White Tim O. , Kelly Michael B. , Tornetta Paul ,   and SPARTA Investigators
Published: October 2022

Objectives:

To delineate whether a “safe” window exists for timing from definitive fixation to definitive soft tissue coverage in the treatment of open tibial diaphyseal fractures requiring flap coverage.

Design:

International multicenter, retrospective comparative cohort study.

Patients/Participants:

Three hundred and seventy-three (n = 373) patients who sustained an open tibial shaft fracture requiring flap coverage.

Methods:

We evaluated the deep infection rates based on the timing between the definitive fixation and flap coverage. We determined several intervals of time from the day of definitive fixation (regardless of time from injury) and flap coverage. If performed on the same operative setting these were considered day 0. We evaluated coverage after 2 and 5 days from definitive fixation based on time versus infection rate curve inflection points. We adjusted for time to debridement and antibiotics within an hour.

Main Outcome Measurement:

Deep infection after definitive fixation and flap coverage.

Results:

The mean age of the cohort was 42.4 years (SD = 18.2) and 270 were male (72.4%). The deep infection rate after flap coverage was 20.6% (77/373). Definitive fixation to flap coverage time of up to 2 days was not associated with an increased risk of infection [relative risk (RR) = 1.12; 95% confidence interval, 0.92–1.37; P = 0.26]. There was an increased risk of deep infection for more than 2 days (RR = 1.59) and >5 days (RR = 1.64).

Conclusion:

This study observed a “safe” window of up to 2 days between definitive fixation and flap coverage in open tibial shaft fractures requiring coverage before a statistical increase in risk of deep infection rate occurred.

Level of Evidence:

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.