bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of the effect of kinetin against formic acid toxicity in chicken embryo model
Authors: Amini Mehran , Zadeh‐Hashem Elham , Allymehr Manoochehr
Published: March 2022

The current study was designed to investigate the in ovo injection of formic acid (FA) on hatchability rate (HR; Experiment 1) and the potential ameliorative role of kinetin concurrent with FA on biochemical parameters of hatched broilers (Experiment 2). In Experiment 1, live embryonated eggs (n = 280; Day 4 of incubation) were in ovo injected with 0.03, 0.06, 0.125, 0.25, 0.50, 1, 2, 4, 8, 16 and 32 m
m FA. In Experiment 2, intra‐yolk‐sac administration of toxic doses of FA (2 m
m) concurrent with kinetin at 50, 100 or 200 µ
m were evaluated on hatched embryos. The amount of malondialdehyde (MDA), total antioxidant capacity (TAC), total nitrate–nitrite (TNN), total lipid hydroperoxide (TLHP) and superoxide dismutase (SOD) activity was measured in serum, liver, heart and brain tissues. The results revealed that injection of 2 mM FA significantly increased mortality compared to the control group (p < 0.05). Concurrent administration of 50 or 100 µ
m kinetin + 2 m
m FA increased HR to 10% and 20% compared to the FA‐alone‐treated group, respectively. Intra‐yolk‐sac‐received FA group showed greater amounts of MDA, TLHP and TNN and lesser amounts of TAC and SOD activity in serum and tissue samples of liver, heart and brain compared to control groups (p < 0.001). In comparison to the FA‐alone‐treated group, all doses of kinetin were able to increase the TAC levels in serum and tissue samples when administered concurrently with FA. The doses of 50 and 100 µ
m kinetin were efficacious to ameliorate the toxic role of FA injection on SOD activities (p < 0.001). Co‐injection of 100 µ
m kinetin plus FA significantly reduced the amounts of MDA, TNN and TLHP in measured samples compared to the FA‐alone‐injected group (p < 0.001). Our results indicated that kinetin (especially at 100 µ
m doses) would ameliorate the toxic effects of FA on developing live chicken embryos.
Trends in rural‐urban disparities among surgical specialties treating cancer, 2004‐2017
Authors: Herb Joshua , Holmes Mark , Stitzenberg Karyn
Published: March 2022

Purpose

We evaluated temporal trends in rural‐urban disparities of the surgeon supply among surgeons commonly treating patients with cancer.

Methods

We performed a retrospective observational study of county‐level workforce changes from 2004 to 2017 using the Area Health Resource File. We calculated physician density (providers/100,000 population) for each specialty by rural and urban counties using the 2003 Rural‐Urban Commuting Codes (RUCC), and evaluated percent changes in the rural‐urban disparity in physician density. Secondary analyses evaluated these changes by Census region. Additionally, Gini indices were calculated by year and RUCC to evaluate the workforce inequality within rural areas.

Findings

Total surgical specialist density declined in rural areas from 16 to 14 per 100,000 population, and declined slightly from 33 to 31 per 100,000 population in urban areas, for a rural‐urban disparity increase of 8% (95% CI 5%,10%). Among specific specialties, the percentage increase in the rural‐urban workforce supply disparity was largest for colorectal surgeons and general surgeons at 66% (95% CI 51%,80%) and 72% (95% CI 58%,86%), respectively, although absolute changes were small. Regional heterogeneity of the workforce was higher for rural areas than urban areas.

Conclusions

Changes in the rural‐urban physician workforce disparities over time are dependent upon specialty, region, and local community factors. This highlights how surgical workforce policy should be oriented to the local area circumstances.
Metaphilosophical considerations on the question of life’s meaning
Authors: Waghorn Nicholas
Published: March 2022

In a recent book, T. J. Mawson has carefully argued, in opposition to the majority of philosophers, that the question “What is the meaning of life?” has more than one interpretation, and so more than one answer. He is anxious, however, that this question not be attributed too many interpretations, on pain of vacuity. This article aims to show that Mawson's attempts to restrict the number of interpretations of the question “What is the meaning of life?” are unsuccessful as they stand, and that there are independent reasons for believing that a limit cannot be placed on the number of such interpretations. Only by paying attention to the more general metaphilosophical issues surrounding our choice of philosophical methodology is there any possibility of restricting those interpretations, and making sense of the question.
Reframing Turkey, Istanbul and national identity: Ottoman history, ‘chosen people’ and the opening of shrines in 1950
Authors: Beyinli Gökçen
Published: March 2022

This article explores the reopening of certain shrines in Istanbul in 1950 as a result of the amendment to Law 677, which in 1925 had closed all shrines in the country and banned visits to them. Drawing on previously untapped archival evidence and combining an analysis at both the macro‐level (nation‐state in a global world) and micro‐level (Istanbul as local and shrines as sites), I discuss changes in cultural policies, historiography and Turkish foreign policy and make use of the contributions of ethno‐symbolic and social constructionist approaches of nationalism theories. I contend that during the transition to the multi‐party system, ‘chosen’ shrines were used as tools to reattach Ottoman roots to Turkish national identity as ‘Turks’ and ‘Muslims’ and reposition Turkey as a strong nation‐state in the new global order. Furthermore, I demonstrate how the former multi‐ethnic and multi‐religious capital, Istanbul, became a part of the national territory as a legitimate Turkish and Muslim city.
OsbHLH061 links TOPLESS/TOPLESS‐RELATED repressor proteins with POSITIVE REGULATOR OF IRON HOMEOSTASIS 1 to maintain iron homeostasis in rice
Authors: Wang Wujian , Ye Jun , Xu Heng , Liu Xi , Fu Yue , Zhang Hui , Rouached Hatem , Whelan James , Shen Zhenguo , Zheng Luqing
Published: March 2022

As excess iron (Fe) is toxic, uptake of this essential micronutrient must be tightly controlled. Previous studies have shown that Oryza sativa (rice) POSITIVE REGULATOR OF IRON HOMEOSTASIS1 (OsPRI1) acts upstream of the iron‐related transcription factor 2 (OsIRO2) and OsIRO3 to positively regulate root‐to‐shoot Fe translocation. However, as expression of OsPRI1 is constitutive it is unclear how the Fe‐deficiency response is turned off to prevent toxicity when Fe is sufficient.

The bHLH transcription factor OsbHLH061 interacts with OsPRI1, and this study used molecular, genetics, biochemical and physiological approaches to functionally characterise OsbHLH061 and how it affects Fe homeostasis.

OsbHLH061 knockout or overexpression lines increase or decrease Fe accumulation in shoots respectively. Mechanistically, OsbHLH061 expression is upregulated by high Fe, and physically interacts with OsPRI1, the OsbHLH061–OsPRI1 complex recruits TOPLESS/TOPLESS‐RELATED (OsTPL/TPR) co‐repressors to repress OsIRO2 and OsIRO3 expression. The OsbHLH061 ethylene‐responsive element‐binding factor‐associated amphiphilic repression (EAR) motif is required for this transcriptional repression activity.

These results define a functional OsTPL/TPR–OsbHLH061–OsPRI1–OsIRO2/3 module that negatively controls long‐distance transport of Fe in plants for adaptation to changing Fe environments and maintain Fe homeostasis in rice.
Biomimetic approach to articular cartilage tissue engineering using carbon nanotube–coated and textured polydimethylsiloxane scaffolds
Authors: Elídóttir Katrín Lind , Scott Louie , Lewis Rebecca , Jurewicz Izabela
Published: March 2022

There is a significant need to understand the complexity and heterogeneity of articular cartilage to develop more effective therapeutic strategies for diseases such as osteoarthritis. Here, we show that carbon nanotubes (CNTs) are excellent candidates as a material for synthetic scaffolds to support the growth of chondrocytes—the cells that produce and maintain cartilage. Chondrocyte morphology, proliferation, and alignment were investigated as nanoscale CNT networks were applied to macroscopically textured polydimethylsiloxane (PDMS) scaffolds. The application of CNTs to the surface of PDMS‐based scaffolds resulted in an up to 10‐fold increase in cell adherence and 240% increase in proliferation, which is attributable to increased nanoscale roughness and hydrophilicity. The introduction of macroscale features to PDMS induced alignment of chondrocytes, successfully mimicking the cell behavior observed in the superficial layer of cartilage. Raman spectroscopy was used as a noninvasive, label‐free method to monitor extracellular matrix production and chondrocyte phenotype. Chondrocytes on these scaffolds successfully produced collagen, glycosaminoglycan, and aggrecan. This study demonstrates that introducing physical features at different length scales allows for a high level of control over tissue scaffold design and, thus, cell behavior. Ultimately, these textured scaffolds can serve as platforms to improve the understanding of osteoarthritis and for early‐stage therapeutic testing.
A cell wall‐anchored glycoprotein confers resistance to cation stress in Actinomyces oris biofilms
Authors: Al Mamun Abu Amar M. , Wu Chenggang , Chang Chungyu , Sanchez Belkys C. , Das Asis , Ton‐That Hung
Published: March 2022

Actinomyces oris plays an important role in oral biofilm development. Like many gram‐positive bacteria, A. oris produces a sizable number of surface proteins that are anchored to bacterial peptidoglycan by a conserved transpeptidase named the housekeeping sortase SrtA; however, the biological role of many A. oris surface proteins in biofilm formation is largely unknown. Here, we report that the glycoprotein GspA—a genetic suppressor of srtA deletion lethality—not only promotes biofilm formation but also maintains cell membrane integrity under cation stress. In comparison to wild‐type cells, under elevated concentrations of mono‐ and divalent cations the formation of mono‐ and multi‐species biofilms by mutant cells devoid of gspA was significantly diminished, although planktonic growth of both cell types in the presence of cations was indistinguishable. Because gspA overexpression is lethal to cells lacking gspA and srtA, we performed a genetic screen to identify GspA determinants involving cell viability. DNA sequencing and biochemical characterizations of viable clones revealed that mutations of two critical cysteine residues and a serine residue severely affected GspA glycosylation and biofilm formation. Furthermore, mutant cells lacking gspA were markedly sensitive to sodium dodecyl sulfate, a detergent that solubilizes the cytoplasmic membranes, suggesting the cell envelope of the gspA mutant was altered. Consistent with this observation, the gspA mutant exhibited increased membrane permeability, independent of GspA glycosylation, compared to the wild‐type strain. Altogether, the results support the notion that the cell wall‐anchored glycoprotein GspA provides a defense mechanism against cation stress in biofilm development promoted by A. oris.
Recurrent ventricular arrhythmia in an ICD recipient: What is the mechanism?
Authors: Sabbag Avi , Beinart Roy , Ollitrault Pierre
Published: March 2022

None.
Family involvement in psychotherapy for depression in children and adolescents: Systematic review and meta‐analysis
Authors: Dippel Nele , Szota Katharina , Cuijpers Pim , Christiansen Hanna , Brakemeier Eva‐Lotta
Published: March 2022

Purpose

Depressive disorders in children and adolescents have an enormous impact on their general quality of life. There is a clear need to effectively treat depression in this age group. Effects of psychotherapy can be enhanced by involving caregivers. In our systematic review and meta‐analysis, we examine for the first time the effects of caregiver involvement in depression‐specific interventions for children and adolescents.

Methods

We included randomized controlled trials examining the effects of interventions for children and adolescents with depression involving their caregivers or families compared to interventions without including caregivers. Primary outcome was the severity of childhood and adolescent depression.

Results

Overall, 19 randomized controlled trials could be included (N = 1553) that were highly heterogeneous regarding outcome measures or the extent of caregiver integration. We were able to include k = 17 studies in our meta‐analysis and find a small but significant effect for family‐involved interventions against active control conditions without family‐involvement at post intervention (α = 0.05, d = 0.34; [0.07; 0.60]; p = .01).

Conclusions

We detected an overall significant but small effect of family/caregivers’ involvement compared to control groups without it. Structured, guideline‐based research is urgently needed to identify for which children/adolescents with depression, under what circumstances, and in what form the family should be effectively involved in their psychotherapy.
Silicon confers aluminium tolerance in rice via cell wall modification in the root transition zone
Authors: Jiang Dexing , Wu Huihui , Cai Hui , Chen Guoxiang
Published: March 2022

The root‐apex transition zone (TZ), the major perception site for aluminium (Al) toxicity, is crucial for the Al‐induced root‐growth inhibition, while the mechanism underlying silicon‐mediated alleviation of Al toxicity in the TZ is largely unknown. In this study, the role of silicon (Si) in alleviating Al‐induced damage in the TZ and root‐growth inhibition of rice was investigated. We found that Si had direct alleviative effect on Al toxicity as revealed by less root growth‐inhibition, Al accumulation, and callose formation. Si reversed Al‐induced decreases of the cell wall elongation and extensibility, and reduced Al‐induced increments of cell wall polysaccharides in the TZ. The similar distribution patterns of Al and Si in the cell wall indicated that Si might detoxify Al by forming hydroxyaluminumsilicates in the apoplast of the root‐apex TZ. Moreover, the wall‐bound form of Si reduced Al binding sites, thereby reducing the capability of Al bound to the cell wall. These results suggest that Si‐mediated cell wall modification in the TZ alleviates Al‐induced root‐growth inhibition in rice involving the promotion of cell wall extensibility and the decrease of Al accumulation in the cell wall.
Genome‐wide characterization of nuclear factor Y transcription factors in Fagopyrum tataricum
Authors: Zhang Ling , Yung Wai‐Shing , Sun Wei , Li Man‐Wah , Huang Mingkun
Published: March 2022

The nuclear factor Y (NF‐Y) is an important transcription factor family that regulates plant developmental processes and abiotic stress responses. Currently, genome‐wide studies of the NF‐Y family are limited in Fagopyrum tataricum, an important economic crop. Based on the released genome assembly, we predicted a total of 38 NF‐Y encoding genes (FtNF‐Ys), including 12 FtNF‐YAs, 18 FtNF‐YBs, and eight FtNF‐YCs subunits, in F. tataricum. Phylogenetic tree and sequence alignments showed that FtNF‐Ys were conserved between F. tataricum and other species. Tissue expressions and network analyses suggested that FtNF‐Ys might be involved in regulating developmental processes in different tissues. Several FtNF‐YAs and FtNF‐Ybs were also potentially involved in light response. In addition, FtNF‐YC‐like1 and FtNF‐YC‐like2 partially rescued the late flowering phenotype in nf‐yc1 nf‐yc3 nf‐yc4 nf‐yc9 (ycQ) mutant in Arabidopsis thaliana, supporting a conserved role of FtNF‐Ys in regulating developmental processes. Together, the genomic information provides a comprehensive understanding of the NF‐Y transcription factors in F. tataricum, which will be useful for further investigation of their functions in F. tataricum.
Characteristics of statistical literacy skills from the perspective of critical thinking
Authors: Koga Shunya
Published: March 2022

Statistical literacy is generally defined as the ability to interpret and evaluate statistical information critically. It is regarded as a higher‐order literacy competence that includes critical thinking. While previous studies have illustrated the concept of statistical literacy, statistical literacy skills have not been sufficiently explored from the perspective of critical thinking research. To fill this gap, this study presents a framework for critical thinking skills in statistical literacy. The characteristics of general critical thinking skills were organized. Based on these characteristics, the researcher extracted sentences related to such skills from selected textbooks. As a result, eight aspects of critical thinking skills in statistical literacy were identified.
SCIENCE, RELIGION, AND HUMAN IDENTITY: CONTRIBUTIONS FROM THE SCIENCE AND RELIGION FORUM
Authors: Lawson Finley
Published: March 2022

The Science and Religion Forum promotes discussion on issues at the interface of science and religion. The forum membership is diverse including professionals, academics, clergy, and interested lay people and each year it holds a conference to encourage discussion and exploration of issues that arise at the interface of science and religion. This article provides an overview of the online conference that took place in May 2021 and introduces this thematic section that includes six articles from the conference.
Netholism and Technological Interference as Manifestations of Communication in the Digital Environment
Authors: Hladíková Vladimíra , Madleňák Adam
Published: March 2022

The Internet, communication in cyberspace, digital technologies and smart devices have a stable place in the educational process moreover due to the COVID-19 pandemic. They bring several advancements and benefits, quick search for current information and their immediate availability. In addition to the positives, there are several risks associated with the Internet, which are even more dramatic in connection with technological interference, in which users of technologies and the Internet are disturbed through various applications or notifications. One of the extremely significant risks is the phenomenon of netholism, which is gaining even more risk in connection with the educational process, as its negative consequences in this area (multitasking, procrastination, problems with concentration, comprehension of texts, etc.) are proven, especially among university students. It can be confirmed that the Internet causes a certain transformation in human cogitation, the way of thinking and perception. The aim of this paper is to examine the phenomenon of netholism and its impact on the education of university students from a theoretical and empirical point of view. The research sample consists of 785 respondents, qualitative methods (phenomenological and hermeneutic approach) and a quantitative research strategy in the form of a questionnaire were used. The findings of the research are presented verbally and graphically, in the conclusion, proposals are formulated to improve the current situation with an appeal to media education and literacy.
Os Reflexos da Sociedade Patriarcal na Divisão Sexual do Trabalho e sua Influência no Judiciário Trabalhista
Authors: Martins Luísa Lima Bastos , Lima Anne Floriane da Escóssia , Lemos Maria Cecilia de Almeida Monteiro
Published: March 2022

A partir de uma perspectiva interseccional que correlaciona gênero, classe social e raça, desenvolvida por Heleieth Saffioti, e da análise de dados coletados nas estatísticas do Conselho Superior da Justiça do Trabalho (2019) e do Tribunal Superior do Trabalho (março de 2021), o artigo se propõe a retratar o atual perfil da Justiça do Trabalho, de forma a possibilitar uma reflexão sobre a influência da estrutura social patriarcal na sua configuração desigual, e os desafios que se apresentam para a superação das desigualdades de gênero nas carreiras do Poder Judiciário. Por fim, destaca as promessas do Estado Democrático de Direito em vista da eliminação de todas as formas de discriminação e a redução das desigualdades, e conclui pela necessária implementação de políticas públicas pelo Poder Judiciário voltadas a dar efetividade aos compromissos constitucionais para a promoção da igualdade de gênero assumidos pelo Brasil.
Concordância Prática no Pensamento Jurídico-Constitucional de Konrad Hesse
Authors: Hoffmann-Riem Wolfgang
Published: March 2022

O presente artigo aborda a origem, o desenvolvimento teórico e a aplicação judicial do princípio da concordância prática no Direito Constitucional alemão, a partir do pensamento de Konrad Hesse. O texto analisa a forma como o princípio da concordância prática foi acolhido no âmbito acadêmico e a sua posterior aplicação pelo Tribunal Constitucional alemão, sua inter-relação com o princípio da proporcionalidade, as críticas elaboradas a ele, bem como as suas possibilidades de realização em face dos desafios originados pela assim chamada Legal Technology.
Desde uma Fatura de Eletricidade Não Paga Até ao Primado do Direito Europeu: Foi Assim Que Surgiu a Jurisprudência Costa c. ENEL
Authors: Arena Amadeo
Published: March 2022

Embora a jurisprudência Costa c. ENEL seja o ponto de partida da maioria das discussões sobre o princípio do primado, a génese processual deste caso é, de certa forma, ainda pouco conhecida. O que levou Flaminio Costa a processar a Edison volta por uma fatura de apenas ₤1.925 (hoje, cerca de €22)? Porque é que o Julgado de paz de Milão decidiu envolver tanto o Tribunal Constitucional da República Italiana quanto o Tribunal de Justiça das Comunidades Europeias em uma disputa, aparentemente, “trivial”? E porque é que esses Tribunais adoptaram decisões tão divergentes? Finalmente, como terminou o processo judicial interno na sequência do acórdão do Tribunal de Justiça? Com base em documentos judiciais parcialmente inéditos e graças a entrevistas com algumas das partes envolvidas, essa contribuição pretende lançar luz sobre alguns aspetos ainda pouco conhecidos do caso Costa c. ENEL, no contexto da nacionalização da eletricidade na Itália, no auge da Guerra Fria, e avaliar a contribuição que esta jurisprudência e o seu “arquiteto”, Gian Galeazzo Stendardi, deram para a afirmação do princípio do primado.
Derecho Penal Ambiental Español
Authors: Martos Nuñez Juan Antonio
Published: March 2022

Derecho Penal Ambiental Español
Thermal Performances Assessment and Improvement of Hollow Concrete Blocks Commonly Used in Morocco: Experimental and Numerical Approach
Authors: Ouakarrouch Mohamed , Laaroussi Najma , Garoum Mohammed , Hajji Amine
Published: March 2022

In the present study, experimental and numerical studies are conducted to identify and improve the thermal properties of the most commonly used hollow concrete blocks in Morocco. The experimental approach consists of characterizing the thermal conductivity and thermal capacity of the basic materials using the guarded hot plate and the differential calorimeter, respectively. The obtained properties have been exploited as input data in the numerical approach to investigate the coupled heat transfer through the concrete blocks using the approximation calculation method suggested by EN ISO 6946, and the three-dimensional numerical simulations using the commercial software ansys fluent. The obtained results showed that the average differences between the 1D and 3D calculations are less than 7.5% concerning the five different studies. In addition, the increase in the width and the number of cavities leads to gain a significant decrease in heat loss and an increase in thermal resistance. For block B4 improvement, the cavities with the previously characterized insulation have been partially filled. The proposed technique ensure high thermal performance by reducing the heat flow at 32%, which increased the thermal resistance of the block by 40.5%.
A Non-Parametric Histogram Interpolation Method for Design Space Exploration
Authors: Pepper Nick , Montomoli Francesco , Sharma Sanjiv
Published: March 2022

A novel algorithm is presented to aid designers during the conceptual design phase of a new engineering product by rapidly assessing new areas of the design space. The algorithm presented here develops a polynomial chaos-based meta-model that allows the designer to estimate the probability distribution for a candidate design’s performance without requiring additional experiments or simulations. Probabilistic equivalence is used to map either a probability density function or a cumulative distribution function, continuous functions, into a reduced space in which interpolation functions can be developed. Data harvested from experiments or evaluations of an expensive computer code are used to train the meta-model. An advantage of this method over other histogram interpolation methods is that it is non-parametric: the training data are not assumed to belong to a particular family of probability distribution. The algorithm was validated using a standard benchmark test with synthetic data in a continuous-discrete design space. Finally, we exploited the variance of the Gaussian process emulators used as interpolation functions in order to develop a statistic that quantified the level of uncertainty associated with the algorithm’s estimates. This is a key feature if the algorithm is to be of practical use.
Particle Loading Effects on Additively Manufactured and Laser Cured Medical Grade Silicone
Authors: Porter Daniel A. , Davis Nicholas E. , Hejny Tristan , Takacs Alison , Bunton Caleb M. , Krueger Paul S. , Son David Y. , Csaky Karl
Published: March 2022

A proposed benefit to additive manufacturing (AM) silicone components is the ability to selectively add fillers such as agents to make drug delivery devices. Laser curing silicones have benefits such as selective or graded curing of specific locations in the part. A challenge with high-temperature extrusion-based AM processes is understanding how particles of various thermal sensitivities, sizes, and loading amounts may affect the AM build parameters, polymer crosslink densities, and final products produced. This article investigates the effect of particle loading on laser-cured medical-grade silicone. Die swelling of silica gel-loaded silicone, chosen as a relatively nonthermally sensitive representative filler for drug agents, was evaluated as a function of extrusion speed, particle size, and particle loading amount. A design of experiments (DoE) on silica gel-loaded samples through tetrahydrofuran (THF) swell studies was done to explore how layer height, particle size, and particle loading amount may affect crosslink density. Last, the AM process with the female hormone 2-methoxyestradiol (2-Me2) and the drug Cyclosporin was investigated using nuclear magnetic resonance (NMR) spectroscopy and high-performance liquid chromatography (HPLC) elution to observe potential alterations of the final product. The results show promise for drug-loaded silicone samples fabricated using an extrude and laser curing AM technique.
Statistically robust estimation of source bearing via minimizing the Bhattacharyya distance
Authors: Ma Qian , Xu Wen , Zhou Yue
Published: March 2022

Source bearing estimation is a common technique in acoustic array processing. Many methods have been developed and most of them exploit some underlying statistical model. When applied to a practical system, the robustness to model mismatch is of major concern. Traditional adaptive methods, such as the minimum power distortionless response processor, are notoriously known for their sensitivity to model mismatch. In this paper, a parameter estimator is developed via the minimum Bhattacharyya distance estimator (MBDE), which provides a measure of the divergence between the assumed and true probability distributions and is, thus, capable of statistically matching. Under a Gaussian random signal model typical of source bearing estimation, the MBDE is derived in terms of the data-based and modeled covariance matrices without involving matrix inversion. The performance of the MBDE, regarding the robustness and resolution, is analyzed in comparison with some of the existing methods. A connection with the Weiss-Weinstein bound is also discussed, which gives the MBDE an interpretation of closely approaching a large-error performance bound. Theoretical analysis and simulations of bearing estimation using a uniform linear array show that the proposed method owns a considerable resolution comparable to an adaptive method while being robust against statistical mismatch, including covariance mismatch caused by snapshot deficiency and/or noise model mismatch.
Supplemental Material: Late Cretaceous time-transgressive onset of Laramide arch exhumation and basin subsidence across northern Arizona–New Mexico, USA, and the role of a dehydrating Farallon flat slab
Authors: Thacker Jacob O. , al. et
Published: March 2022

Additional text, tables, and figures including PyCool instructions and code, HeFTy inverse and forward models, basin stratigraphy and data, and onset estimates with notes.
Training physicians in providing complex information to patients with multiple sclerosis: a randomised controlled trial
Authors: Nordfalk Jenny M , Holmøy Trygve , Thomas Owen , Nylenna Magne , Gulbrandsen Pal
Published: March 2022

Objective

To evaluate the effect of a specific communication training for neurologists on how to provide complex information about treatment options to patients with multiple sclerosis (MS).

Design

Single-centre, single-blind, randomised controlled trial.

Setting

One university hospital in Norway.

Participants

Thirty-four patients with early-stage MS.

Intervention

A 3-hour training for neurologists on how to provide complex information about MS escalation therapy.

Main outcome measures

Patient recall rate, measured with a reliable counting system of provided and recalled information about drugs.

Secondary outcome measures

Number of information units provided by the physicians. Effects on patient involvement through questionnaires.

Methods

Patients with MS were instructed to imagine a disease development and were randomised and blinded to meet a physician to receive information on escalation therapy, before or after the physician had participated in a 3-hour training on how to provide complex information. Consultations and immediate patient recall interviews were video-recorded and transcribed verbatim.

Results

Patient recall rate was 0.37 (SD=0.10) pre-intervention and 0.39 (SD=0.10) post-intervention. The effect of the intervention on recall rate predicted with a general linear model covariate was not significant (coefficient parameter 0.07 (SE 0.04, 95% CI (−0.01 to 0.15)), p=0.099).

The physicians tended to provide significantly fewer information units after the training, with an average of 91.0 (SD=30.3) pre-intervention and 76.5 (SD=17.4) post-intervention; coefficient parameter −0.09 (SE 0.02, 95% CI (−0.13 to −0.05)), p<0.001. There was a significant negative association between the amount of provided information and the recall rate (coefficient parameter −0.29 (SE 0.05, 95% CI (−0.39 to −0.18)), p<0.001). We found no significant effects on patient involvement using the Control Preference Scale, Collaborate or Four Habits Patient Questionnaire.

Conclusion

A brief course for physicians on providing complex information reduced the amount of information provided, but did not improve patient recall rate.

Trial registration number

ISRCTN42739508.
Study protocol: navigating access to gender care in Ireland—a mixed-method study on the experiences of transgender and non-binary youth
Authors: Kearns Seán , Houghton Catherine , O’Shea Donal , Neff Karl
Published: March 2022

Introduction

There has been a global increase in demand for gender-specific healthcare services and a recognition that healthcare access is complex and convoluted, even in countries with well-developed healthcare services. Despite evidence in Ireland supporting the improvement in physical and mental health following access to gender care, little is known about the local healthcare navigation challenges. Internationally, research focuses primarily on the experience of service users and omits the perspective of other potential key stakeholders. Youth experiences are a particularly seldom-heard group.

Methods and analysis

This study will use a sequential exploratory mixed-methods design with a participatory social justice approach. The qualitative phase will explore factors that help and hinder access to gender care for young people in Ireland. This will be explored from multiple stakeholders’ perspectives, namely, young people, caregivers and specialist healthcare providers. Framework analysis will be used to identify priorities for action and the qualitative findings used to build a survey tool for the quantitative phase. The quantitative phase will then measure the burden of the identified factors on healthcare navigation across different age categories and gender identities (transmasculine vs transfeminine vs non-binary).

Ethics and dissemination

This study has been approved by St Vincent’s Hospital Research Ethics Committee (RS21-019), University College Dublin Ethics Committee (LS-21-14Kearns-OShea) and the Transgender Equality Network Ireland’s Internal Ethics Committee (TIECSK). We aim to disseminate the findings through international conferences, peer-review journals and by utilisation of expert panel members and strategic partners.
RETurn to work After stroKE (RETAKE) Trial: protocol for a mixed-methods process evaluation using normalisation process theory
Authors: Radford Kathryn A , McKevitt Christopher , Clarke Sara , Powers Katie , Phillips Julie , Craven Kristelle , Watkins Caroline , Farrin Amanda , Holmes Jain , Cripps Rachel , McLellan Vicki , Sach Tracey , Brindle Richard , Holloway Ivana , Hartley Suzanne , Bowen Audrey , O'Connor Rory J , Stevens Judith , Walker Marion , Murray John , Shone Angela , Clarke David
Published: March 2022

Objectives

This mixed-method process evaluation underpinned by normalisation process theory aims to measure fidelity to the intervention, understand the social and structural context in which the intervention is delivered and identify barriers and facilitators to intervention implementation.

Setting

RETurn to work After stroKE (RETAKE) is a multicentre individual patient randomised controlled trial to determine whether Early Stroke Specialist Vocational Rehabilitation (ESSVR) plus usual care is a clinically and cost-effective therapy to facilitate return to work after stroke, compared with usual care alone. This protocol paper describes the embedded process evaluation.

Participants and outcome measures

Intervention training for therapists will be observed and use of remote mentor support reviewed through documentary analysis. Fidelity will be assessed through participant questionnaires and analysis of therapy records, examining frequency, duration and content of ESSVR sessions. To understand the influence of social and structural contexts, the process evaluation will explore therapists’ attitudes towards evidence-based practice, competency to deliver the intervention and evaluate potential sources of contamination. Longitudinal case studies incorporating non-participant observations will be conducted with a proportion of intervention and usual care participants. Semistructured interviews with stroke survivors, carers, occupational therapists, mentors, service managers and employers will explore their experiences as RETAKE participants. Analysis of qualitative data will draw on thematic and framework approaches. Quantitative data analysis will include regression models and descriptive statistics. Qualitative and quantitative data will be independently analysed by process evaluation and Clinical Trials Research Unit teams, respectively. Linked data, for example, fidelity and describing usual care will be synthesised by comparing and integrating quantitative descriptive data with the qualitative findings.

Ethics and dissemination

Approval obtained through the East Midlands—Nottingham 2 Research Ethics Committee (Ref: 18/EM/0019) and the National Health ServiceResearch Authority. Dissemination via journal publications, stroke conferences, social media and meetings with national Stroke clinical leads.

Trial registration number

ISRCTN12464275.
Improving safety of unfractionated heparin: a retrospective, quasi-experimental, observational study of the impact of a pocket card and a computerised prescription aid tool in the University Hospitals of Geneva
Authors: Jimaja Wedali E , Stirnemann Jerome , Fontana Pierre , Blondon Katherine S
Published: March 2022

Background

Despite the rapid rise of direct oral anticoagulants, unfractionated heparin (UFH) remains the mainstay anticoagulant in specific situations such as severe renal failure, perioperative setting or in critical care units. However, its titration is often challenging.

Objectives

To investigate the effect of a pocket card and a computerised prescription aid tool (CPAT) on the quality of UFH anticoagulation.

Design

Monocentric retrospective, quasi-experimental, observational study.

Setting

Inpatient primary care centre between 1 January 2016 and 31 December 2019.

Participants

>18 years-old treated with therapeutic UFH for more than 24 hours. There were 819 and 1169 anticoagulation episodes before and after intervention, respectively.

Intervention

In October 2017, we implemented a pocket card with evidence-based recommendation for therapeutic UFH initiation, monitoring and dosing adaptation. In October 2019, we implemented a CPAT in a group subset.

Primary and secondary outcomes

The primary outcome was the time needed to reach a therapeutic anti-Xa before and after the implementation of the pocket card. The secondary outcomes included a subgroup analysis assessing the effect of the CPAT. Other secondary outcomes were the anti-Xa status (infratherapeutic, therapeutic or supratherapeutic) at 7 and 24 hours of UFH treatment.

Results

We found a significant increase in the time to reach therapeutic dosing with pocket card-guided recommendations implementation (10.1 vs 14 hours, HR of 0.8, 95% CI: 0.70 to 0.93). However, the CPAT was associated with a significant decrease in the time needed to reach the therapeutic range (13.9 vs 7.1 hours, HR of 1.74, 95% CI: 1.17 to 2.60).

Conclusion

Although we observed an increase in time to reach therapeutic anti-Xa with the pocket card, possibly due to a selection bias (use of activated partial thromboplastin time for monitoring before the pocket card), the implementation of CPAT significantly decreased the delay for effective therapy. Further studies are needed to confirm these findings, and to determine the optimal initial dose of UFH anticoagulation.
Characterising the use of surgical pathology rush requests: a descriptive analysis and survey
Authors: Tran Christopher , Virine Boris , Gershon Ariel , Kwan Keith F , Ettler Helen C
Published: March 2022

This study aimed to characterise priority or ‘rush’ surgical pathology requests and identify potentially targetable factors. We performed a retrospective descriptive analysis of rush requests at our institution from 2016 to 2019 and conducted a survey asking pathologists about their perspectives on rush cases. There were 3677 rush cases, with case characteristics generally stable over the study period. Two categories of requests were identified based on hospital status; outpatient requests more frequently provided a specific date for diagnosis, while inpatient rush requests generally required a diagnosis as soon as possible. Most pathologists found rush cases to be somewhat more stressful compared with routine cases (65.2%) and found it very or extremely useful to know when a result is needed (86.9%). The use of hospitalisation status, and identifying if results are required by a certain date, may help in more effective triaging of rush surgical pathology cases.
Specific Changes of Erythroid Regulators and Hepcidin in Patients Infected by SARS-COV-2
Authors: Delaye Jean-Baptiste , Alarcan Hugo , Vallet Nicolas , Veyrat-Durebex Charlotte , Bernard Louis , Hérault Olivier , Ropert Martine , Marlet Julien , Gyan Emmanuel , Andres Christian , Blasco Hélène , Piver Eric
Published: March 2022

Iron metabolism is tightly linked to infectious and inflammatory signals through hepcidin synthesis. To date, iron homeostasis during SARS-CoV-2 infection has not yet been described. The aim of this study is to characterize the hepcidin and erythroid regulators (growth differentiation factor 15 (GDF-15) and erythroferrone (ERFE)) by measuring concentrations in plasma in context of COVID-19 disease.

We performed a single-center observational study of patients with COVID-19 to evaluate concentrations of main regulatory proteins involved in iron homeostasis, namely: hepcidin, ERFE and GDF-15. SARS-CoV-2 infection (COVID-19+) was defined by a positive RT-PCR. Sixteen patients with COVID-19+ were gender-matched and age-matched to 16 patients with a sepsis unrelated to SARS-CoV-2 (COVID-19−) and were compared with non-parametric statistic test.

Clinical and hematological parameters, plasma iron, transferrin, transferrin saturation, ferritin, soluble transferrin receptor and C reactive protein were not statistically different between both groups. Median plasma hepcidin concentrations were higher in the COVID-19+ group (44.1 (IQR 16.55–70.48) vs 14.2 (IQR 5.95–18.98) nmol/L, p=0.003), while median ERFE and GDF-15 concentrations were lower in the COVID-19+ group (0.16 (IQR 0.01–0.73) vs 0.89 (IQR 0.19–3.82) ng/mL, p=0.035; 2003 (IQR 1355–2447) vs 4713 (IQR 2082–7774) pg/mL, p=0015), respectively) compared with the COVID-19− group.

This is the first study reporting lower ERFE and GDF-15 median concentrations in patients with COVID-19+ compared with patients with COVID-19−, associated with an increased median concentration of hepcidin in the COVID-19+ group compared with COVID19− group.
Higher Hospital Frailty Risk Score is associated with increased complications and healthcare resource utilization after endovascular treatment of ruptured intracranial aneurysms
Authors: Koo Andrew B , Elsamadicy Aladine A , Renedo Daniela , Sarkozy Margot , Sherman Josiah , Reeves Benjamin C , Havlik John , Antonios Joseph , Sujijantarat Nanthiya , Hebert Ryan , Malhotra Ajay , Matouk Charles
Published: March 2022

Aim

To use the Hospital Frailty Risk Score (HFRS) to investigate the impact of frailty on complication rates and healthcare resource utilization in patients who underwent endovascular treatment of ruptured intracranial aneurysms (IAs).

Methods

A retrospective cohort study was performed using the 2016–2019 National Inpatient Sample database. All adult patients (≥18 years) undergoing endovascular treatment for IAs after subarachnoid hemorrhage were identified using ICD-10-CM codes. Patients were categorized into frailty cohorts: low (HFRS <5), intermediate (HFRS 5–15) and high (HFRS >15). Patient demographics, adverse events, length of stay (LOS), discharge disposition, and total cost of admission were assessed. Multivariate logistic regression analysis was used to identify independent predictors of prolonged LOS, increased cost, and non-routine discharge.

Results

Of the 33 840 patients identified, 7940 (23.5%) were found to be low, 20 075 (59.3%) intermediate and 5825 (17.2%) high frailty by HFRS criteria. The rate of encountering any adverse event was significantly greater in the higher frailty cohorts (low: 59.9%; intermediate: 92.4%; high: 99.2%, p<0.001). There was a stepwise increase in mean LOS (low: 11.7±8.2 days; intermediate: 18.7±14.1 days; high: 26.6±20.1 days, p<0.001), mean total hospital cost (low: $62 888±37 757; intermediate: $99 670±63 446; high: $134 937±80 331, p<0.001), and non-routine discharge (low: 17.3%; intermediate: 44.4%; high: 69.4%, p<0.001) with increasing frailty. On multivariate regression analysis, a similar stepwise impact was found in prolonged LOS (intermediate: OR 2.38, p<0.001; high: OR 4.49, p<0.001)], total hospital cost (intermediate: OR 2.15, p<0.001; high: OR 3.62, p<0.001), and non-routine discharge (intermediate: OR 2.13, p<0.001; high: OR 4.17, p<0.001).

Conclusions

Our study found that greater frailty as defined by the HFRS was associated with increased complications, LOS, total costs, and non-routine discharge.
Prospective study on embolization of intracranial aneurysms with the pipeline device (PREMIER study): 3-year results with the application of a flow diverter specific occlusion classification
Authors: Hanel Ricardo A , Cortez Gustavo M , Lopes Demetrius Klee , Nelson Peter Kim , Siddiqui Adnan H , Jabbour Pascal , Mendes Pereira Vitor , István Istvan Szikora , Zaidat Osama O , Bettegowda Chetan , Colby Geoffrey P , Mokin Maxim , Schirmer Clemens M , Hellinger Frank R , Given Curtis , Krings Timo , Taussky Philipp , Toth Gabor , Fraser Justin F , Chen Michael , Priest Ryan , Kan Peter , Fiorella David , Frei Donald , Aagaard-Kienitz Beverly , Diaz Orlando , Malek Adel M , Cawley C Michael , Puri Ajit S , Kallmes David F
Published: March 2022

Background

The pipeline embolization device (PED; Medtronic) has presented as a safe and efficacious treatment for small- and medium-sized intracranial aneurysms. Independently adjudicated long-term results of the device in treating these lesions are still indeterminate. We present 3-year results, with additional application of a flow diverter specific occlusion scale.

Methods

PREMIER (prospective study on embolization of intracranial aneurysms with pipeline embolization device) is a prospective, single-arm trial. Inclusion criteria were patients with unruptured wide-necked intracranial aneurysms ≤12 mm. Primary effectiveness (complete aneurysm occlusion) and safety (major neurologic event) endpoints were independently monitored and adjudicated.

Results

As per the protocol, of 141 patients treated with a PED, 25 (17.7%) required angiographic follow-up after the first year due to incomplete aneurysm occlusion. According to the Core Radiology Laboratory review, three (12%) of these patients progressed to complete occlusion, with an overall rate of complete aneurysm occlusion at 3 years of 83.3% (115/138). Further angiographic evaluation using the modified Cekirge–Saatci classification demonstrated that complete occlusion, neck residual, or aneurysm size reduction occurred in 97.1%. The overall combined safety endpoint at 3 years was 2.8% (4/141), with only one non-debilitating major event occurring after the first year. There was one case of aneurysm recurrence but no cases of delayed rupture in this series.

Conclusions

The PED device presents as a safe and effective modality in treating small- and medium-sized intracranial aneurysms. The application of a flow diverter specific occlusion classification attested the long-term durability with higher rate of successful aneurysm occlusion and no documented aneurysm rupture.

Trial registration

NCT02186561.