bluuebunny/crossref_metadata_2025 huggingface dataset:
Population pharmacokinetics of subcutaneous infliximab CT‐P13 in Crohn’s disease and ulcerative colitis
Authors: Hanzel Jurij , Bukkems Laura H. , Gecse Krisztina B. , D’Haens Geert R. , Mathôt Ron A. A.
Published: September 2021

Background

Infliximab is a chimeric monoclonal antibody against tumour necrosis factor‐alpha for the treatment of Crohn's disease (CD) and ulcerative colitis (UC). Recently, a subcutaneous formulation of CT‐P13, an infliximab biosimilar, was approved for clinical use.

Aims

To characterise CT‐P13 pharmacokinetics (PK) and its clinically relevant determinants after subcutaneous administration through population PK modelling.

Methods

Data from a two‐part Phase I study with intravenous (5 mg/kg) and variable maintenance subcutaneous dosing of CT‐P13 with frequent PK sampling in patients with CD or UC were used. Population PK analysis was conducted by non‐linear mixed effects modelling. Covariates affecting PK parameters were chosen based on their clinical relevance (effect size of ≥20%) using a full fixed‐effect modelling approach.

Results

CT‐P13 PK was described by a two‐compartment model with linear elimination. The half‐life in a typical 70 kg patient with serum albumin of 44 g/L was 10.8 days. The typical value for clearance was 0.355 L/d, absorption constant 0.273/d, bioavailability 79.1%, central volume of distribution 3.10 L and peripheral volume of distribution 1.93 L. Clinically relevant covariates affecting clearance were body weight (+43.2% from 70 to 120 kg), the presence of anti‐drug antibodies (+39%) and serum albumin concentration (+30.1% from 44 to 32 g/L). Simulated drug exposure was comparable between routes of administration for patients weighing 50 or 70 kg, but lower with subcutaneous dosing in patients weighing 120 kg.

Conclusions

This first population PK model for subcutaneous CT‐P13 supports fixed subcutaneous maintenance dosing, although heavy patients had lower cumulative drug exposure.
The influence of Alasdair MacIntyre’s “After Virtue” book on business ethics studies: A citation concept analysis
Authors: Akgün Ali E. , Keskin Halit , Fidan Selahaddin Samil
Published: September 2021

Alasdair MacIntyre’s title, After Virtue: A Study in Moral Theory (AV), is a thought‐provoking, influential, ground‐breaking title that contributes much to business ethics studies. However, to date, there has not been any systematic and comprehensive study that has examined AV’s overall impact on the business ethics landscape. This study thus offers specific and rich information about AV’s realized contribution to business ethics over the past 20 years. First, using citation concept analysis (CCA), which refers to a content analysis of statements surrounding in‐text citations of AV in articles referring to the primary source, we reveal which AV contents have been either frequently cited or rarely cited. Our findings indicate that although researchers have cited considerably rich and diverse content from AV, there remains a discrepancy for citation contexts when compared to AV’s original content related to MacIntyre’s multi‐level virtue conceptualization. Secondly, using citation depth analysis for how citations of AV spread through a primary source in one of the three categories, for example, limited, intermediate, and comprehensive, we find that AV content has been increasingly cited in both an intermediate and a comprehensive way. We discuss the theoretical and practical implications of this offered study in the management and organization studies.
Estimating perinatal critical windows of susceptibility to environmental mixtures via structured Bayesian regression tree pairs
Authors: Mork Daniel , Wilson Ander
Published: September 2021

Maternal exposure to environmental chemicals during pregnancy can alter birth and children's health outcomes. Research seeks to identify critical windows, time periods when exposures can change future health outcomes, and estimate the exposure–response relationship. Existing statistical approaches focus on estimation of the association between maternal exposure to a single environmental chemical observed at high temporal resolution (e.g., weekly throughout pregnancy) and children's health outcomes. Extending to multiple chemicals observed at high temporal resolution poses a dimensionality problem and statistical methods are lacking. We propose a regression tree–based model for mixtures of exposures observed at high temporal resolution. The proposed approach uses an additive ensemble of tree pairs that defines structured main effects and interactions between time‐resolved predictors and performs variable selection to select out of the model predictors not correlated with the outcome. In simulation, we show that the tree‐based approach performs better than existing methods for a single exposure and can accurately estimate critical windows in the exposure–response relation for mixtures. We apply our method to estimate the relationship between five exposures measured weekly throughout pregnancy and birth weight in a Denver, Colorado, birth cohort. We identified critical windows during which fine particulate matter, sulfur dioxide, and temperature are negatively associated with birth weight and an interaction between fine particulate matter and temperature. Software is made available in the R package dlmtree.
Bayesian multiple index models for environmental mixtures
Authors: McGee Glen , Wilson Ander , Webster Thomas F. , Coull Brent A.
Published: September 2021

An important goal of environmental health research is to assess the risk posed by mixtures of environmental exposures. Two popular classes of models for mixtures analyses are response‐surface methods and exposure‐index methods. Response‐surface methods estimate high‐dimensional surfaces and are thus highly flexible but difficult to interpret. In contrast, exposure‐index methods decompose coefficients from a linear model into an overall mixture effect and individual index weights; these models yield easily interpretable effect estimates and efficient inferences when model assumptions hold, but, like most parsimonious models, incur bias when these assumptions do not hold. In this paper, we propose a Bayesian multiple index model framework that combines the strengths of each, allowing for non‐linear and non‐additive relationships between exposure indices and a health outcome, while reducing the dimensionality of the exposure vector and estimating index weights with variable selection. This framework contains response‐surface and exposure‐index models as special cases, thereby unifying the two analysis strategies. This unification increases the range of models possible for analysing environmental mixtures and health, allowing one to select an appropriate analysis from a spectrum of models varying in flexibility and interpretability. In an analysis of the association between telomere length and 18 organic pollutants in the National Health and Nutrition Examination Survey (NHANES), the proposed approach fits the data as well as more complex response‐surface methods and yields more interpretable results.
Revisiting Diagnostic performances of serum erythropoïetin level and JAK2 mutation for polycythemias: analysis of a cohort of 1090 patients with red cell mass measurement
Authors: Maslah Nabih , Ravdan Odonchimeg , Drevon Louis , Verger Emmanuelle , Belkhodja Célia , Chomienne Christine , Cassinat Bruno , Kiladjian Jean‐Jacques , Giraudier Stéphane , Schlageter Marie‐Hélène
Published: September 2021

We assessed the diagnostic performances of erythropoietin and JAK2 mutations in 1,090 patients with suspected polycythemia who were referred for red cell mass (RCM) measurement. In patients with a high haematocrit and/or haemoglobin level, a low erythropoietin level (<=3·3 mUI/ml) and JAK2 mutation showed comparable positive predictive value (PPV) for true polycythemia (RCM>=125%), 92·1% and 90% respectively. A very‐low erythropoietin level (<=1·99 mUI/ml) had a PPV of 100% for polycythemia vera (PV) diagnosis. We confirmed the correlations between RCM, erythropoietin and JAK2 variant allelic frequency in PV patients. This study prompts the need to revisit the role of EPO in PV diagnostic criteria.
Evidence for the intrusion of marine Atlantic waters into the West Siberian Arctic during the Middle Pleistocene
Authors: Nazarov Dmitry V. , Nikolskaia Olga A. , Gladysheva Anna S. , Zhigmanovskiy Igor V. , Ruchkin Maksim V. , Merkuljev Aleksei V. , Thomsen Kristina J.
Published: September 2021

Marine sediments occupy a significant portion of the Quaternary succession in the West Siberian Arctic but, until recently, their ages and distributions have been strongly debated. Based on new geological, palaeontological and geochronological data obtained within the last decade, we hereby postulate the following: (i) Two different Pleistocene interglacial marine formations are exposed across the West Siberian Arctic. The older Kheta marine formation, sandwiched between two Middle Pleistocene till beds, yields optically stimulated luminescence (OSL) ages of c. 200 ka (MIS 7). The younger Karginsky/Payuta marine formation, overlying the Middle Pleistocene Taz till, contains a boreal mollusc fauna and has an OSL age of c. 115 ka (MIS 5e). These Middle and Upper Pleistocene marine beds have been correlated across a vast region between the Ob’ and Yenisey estuaries. (ii) The marine transgression during MIS 7 spread as far south into West Siberia as 65°N, almost 1000 km southwards from the present‐day Kara Sea shoreline. Meanwhile, the smaller marine transgression during MIS 5e reached as far south as 68°N. (iii) Both marine formations contain a boreal molluscan fauna, which is not found in the modern Kara Sea but is characteristic of the North Atlantic. We propose that warmer Atlantic waters penetrated much further eastwards during both MIS 7 and MIS 5e than at present. The diagnostic extinct mollusc species Cyrtodaria jenisseae has only been found in the older Kheta marine formation (MIS 7).
Neutrophil-mediated mechanisms of damage and in-vitro protective effect of colchicine in non-vascular Behçet's syndrome
Authors: Bettiol Alessandra , Becatti Matteo , Silvestri Elena , Argento Flavia Rita , Fini Eleonora , Mannucci Amanda , Galora Silvia , Mattioli Irene , Urban Maria Letizia , Malandrino Danilo , Palermo Adalgisa , Taddei Niccolò , Emmi Giacomo , Prisco Domenico , Fiorillo Claudia
Published: September 2021

Behçet's syndrome (BS) is a systemic vasculitis with several clinical manifestations. Neutrophil hyperactivation mediates vascular BS pathogenesis, via both a massive reactive oxygen species (ROS) production and neutrophil extracellular traps (NETs) release. Here, we investigated neutrophil-mediated mechanisms of damage in non-vascular BS manifestations and explored the in-vitro effects of colchicine in counteracting these mechanisms. NETs and intracellular ROS production was assessed in blood samples from 80 BS patients (46 with active non-vascular BS, 34 with inactive disease) and 80 healthy controls. Moreover, isolated neutrophils were incubated for 1 h with an oxidating agent [2,2′-azobis (2-amidinopropane) dihydrochloride; 250 nM] and the ability of pure colchicine pretreatment (100 ng/ml) to counteract oxidation-induced damage was assessed. Patients with active non-vascular BS showed remarkably increased NET levels [21.2, interquartile range (IQR) = 18.3–25.9 mU/ml] compared to patients with inactive disease (16.8, IQR = 13.3–20.2 mU/ml) and to controls (7.1, IQR = 5.1–8.7 mU/ml, p < 0.001]. Also, intracellular ROS tended to increase in active BS, although not significantly. In active non-vascular BS, NETs correlated with neutrophil ROS production (p < 0.001) and were particularly increased in patients with active mucosal (p < 0.001), articular (p = 0.004) and gastrointestinal symptoms (p = 0.006). In isolated neutrophils, colchicine significantly reduced oxidation-induced NET production and cell apoptosis, although not via an anti-oxidant activity. Neutrophil-mediated mechanisms might be directly involved in non-vascular BS, and NETs, more than ROS, might drive the pathogenesis of mucosal, articular and intestinal manifestations. Colchicine might be effective in counteracting neutrophils-mediated damage in BS, although further studies are needed.
Contact allergy to oxidized linalool and oxidized limonene: Patch testing in consecutive patients with dermatitis
Authors: Sukakul Thanisorn , Bruze Magnus , Mowitz Martin , Antelmi Annarita , Bergendorff Ola , Björk Jonas , Dahlin Jakob , Hamnerius Nils , Hauksson Inese , Isaksson Marléne , Lejding Tina , Pontén Ann , Svedman Cecilia
Published: September 2021

Background

Contact allergy to oxidized (ox.) linalool and ox. limonene has been reported to have a high prevalence, raising the question of inclusion into the baseline series. However, several important issues should be clarified and further investigated before inclusion can be warranted.

Objectives

To report the trends of ox. terpenes allergy in patients with dermatitis, features of the patch test reactions, and clinical characteristics of the patients.

Methods

A retrospective analysis of 5773 patients was performed. All patients were patch tested with baseline series, individual ingredients of fragrance mix I and II, ox. linalool, and ox. limonene from 2013 to 2020.

Results

The prevalence rates of contact allergy to ox. linalool and ox. limonene were 7.0% and 5.1%, respectively. Significantly increasing trends of contact allergy were observed. More than 95% of contact allergy cases were identified on Day 3/4. Patients with contact allergy to ox. linalool and ox. limonene were significantly younger than those with contact allergy to other fragrances and were predominantly female. Strong reactions were associated with older age and multiple fragrance allergies.

Conclusions

Contact allergy to ox. linalool and ox. limonene is becoming increasingly important, and findings show intriguing features. More studies concerning the clinical relevance before recommending these substances for screening are required.
‘Let communities do their work’: the role of mutual aid and self‐help groups in the Covid‐19 pandemic response
Authors: Carstensen Nils , Mudhar Mandeep , Munksgaard Freja Schurmann
Published: September 2021

How to respond quickly, effectively, and sensitively to large‐scale crises is debated at length in the aid sector. Institutional focuses on projects and outcomes have led to abundant literature on the efficacy of external interventions, while the actions of individuals and communities to meet their own needs remain under researched. This paper seeks to close the gap by joining global trends and specific case studies to explore the scale, breadth, and characteristics of citizen and community‐led responses to the Covid‐19 pandemic of 2020–21. Using mixed methods, it argues that mutual aid, self‐help, and other spontaneous community measures were vital to the early response to Covid‐19 globally. Such endeavours have limitations, however, which can be strengthened with the right national and international support. The paper concludes by calling on authorities and aid actors to widen their understanding of ‘first response’ and provide meaning ful support to mutual aid and local self‐help initiatives now and in the future.
Amplifying the antidiabetic actions of glucagon‐like peptide‐1: Potential benefits of new adjunct therapies
Authors: Tanday Neil , Flatt Peter R. , Irwin Nigel
Published: September 2021

Clinically approved for the treatment of diabetes and obesity, glucagon‐like peptide‐1 (GLP‐1) receptor agonists display prominent glucose‐ and weight‐lowering effects as well as positive cardioprotective and neuroprotective actions. Despite these benefits, bariatric surgery remains superior in producing robust and sustained weight loss alongside improvements in metabolic control with possible diabetes remission. The current review considers the potential for adjunct therapies to augment the therapeutic actions of GLP‐1 receptor agonists. In this regard, several gut‐derived hormones also, modulated by bariatric surgery, display additive properties when combined with GLP‐1 receptor agonists in both preclinical and clinical studies. In addition, glucocorticoids and oestrogen have shown promise in augmenting the biological actions of GLP‐1 in animal models. Additionally, GLP‐1 efficacy can also be enhanced by use of compounds that prolong GLP‐1 receptor coupling to potentiate downstream receptor signalling. Taken together, therapies that activate GLP‐1 receptor signalling, in combination with various other cell signalling pathways, show potential for treating type 2 diabetes and obesity with superiority over GLP‐1 receptor agonist therapy alone.
Formalizing agricultural rentals in China: Does local public action help?
Authors: Qiu Tongwei , Shi Xinjie , Luo Biliang
Published: September 2021

Motivation

From 2002, local governments and village collectives in China have been allowed and encouraged to facilitate and formalize agricultural land rentals. Before, most temporary land transfers within villages were informal agreements between farmers who knew each other well. Changes were introduced to make it easier for outsiders to rent land, and thereby bring capital and know‐how to the village.

Purpose

This study tests whether public intervention increases market‐based land rentals and how it affects rentals among acquaintances.

Methods and approach

Drawing on data from the 2017 and 2019 China Family Panel Surveys conducted in 29 provinces, ordinary least squares and fixed effect models are used to test the effects of public intervention in agricultural rentals.

Findings

Public intervention increases land rentals and the widespread use of written contracts for defined periods. Rentals between acquaintances within the same village have become more formal, with rents at market levels. When local authorities facilitate land rentals in villages, all rentals become more formal, with market‐based rents.

Policy implications

Public intervention in Chinese agricultural land rental has reduced transaction costs for outsiders, has led to more market‐based rentals, and has facilitated land transfers—in a setting where some farmers are looking to switch from farming to off‐farm work. Policy changes have worked.
The potential role of dexmedetomidine on neuroprotection and its possible mechanisms: Evidence from in vitro and in vivo studies
Authors: Unchiti Kantarakorn , Leurcharusmee Prangmalee , Samerchua Artid , Pipanmekaporn Tanyong , Chattipakorn Nipon , Chattipakorn Siriporn C.
Published: September 2021

Neurological disorders following brain injuries and neurodegeneration are on the rise worldwide and cause disability and suffering in patients. It is crucial to explore novel neuroprotectants. Dexmedetomidine, a selective α2‐adrenoceptor agonist, is commonly used for anxiolysis, sedation and analgesia in clinical anaesthesia and critical care. Recent studies have shown that dexmedetomidine exerts protective effects on multiple organs. This review summarized and discussed the current neuroprotective effects of dexmedetomidine, as well as the underlying mechanisms. In preclinical studies, dexmedetomidine reduced neuronal injury and improved functional outcomes in several models, including hypoxia‐induced neuronal injury, ischaemic‐reperfusion injury, intracerebral haemorrhage, post‐traumatic brain injury, anaesthetic‐induced neuronal injury, substance‐induced neuronal injury, neuroinflammation, epilepsy and neurodegeneration. Several mechanisms are associated with the neuroprotective function of dexmedetomidine, including neurotransmitter regulation, inflammatory response, oxidative stress, apoptotic pathway, autophagy, mitochondrial function and other cell signalling pathways. In summary, dexmedetomidine has the potential to be a novel neuroprotective agent for a wide range of neurological disorders.
Seed movement in small‐scale vegetation restoration
Authors: Elliott Carole P , Commander Lucy E , Williams Matthew R , Golos Peter J
Published: September 2021

Quantifying ecological interactions can inform restoration practitioners of the recovery of ecosystem function in restored areas. Plant–animal interactions that move seeds are critical for plant recruitment, animal food sources and ecosystem function, but seed movement immediately after sowing can affect calculations of seedling emergence in restored areas. We set up seed cafeterias in undisturbed, native vegetation and restored areas to quantify and compare the removal of seeds of eight native plant species of banded ironstone ranges to determine the recovery of this ecological interaction and the potential effect on monitoring protocols. Overall, the average amounts of seeds removed from cafeterias over two days were between 17 and 23%, but this varied considerably between replicates. Seeds with or without a food body (i.e. elaiosome) were both removed from cafeterias by invertebrates. Seeds removed by invertebrates (most likely ants) after surface sowing for restoration are expected to negatively affect calculations of seedling emergence because the known quantity of sown seeds has been reduced, deflating emergence calculations. Restoration protocols should consider the potential negative effect of seed movement on seedling emergence. Encouragingly, these restoration areas have maintained ecological interactions that move seeds in the landscape at comparable levels to undisturbed vegetation.
Long‐term MRI changes in a patient with Kelch‐like protein 11‐associated paraneoplastic neurological syndrome
Authors: Ishikawa Hidehiro , Mandel‐Brehm Caleigh , Shindo Akihiro , Cady Martha A. , Mann Sabrina A. , Niwa Atsushi , Miyashita Koichi , Ii Yuichiro , Zorn Kelsey C. , Taniguchi Akira , Maeda Masayuki , Wilson Michael R. , DeRisi Joseph L. , Tomimoto Hidekazu
Published: September 2021

Background and purpose

The aim of this study was to identify the long‐term radiological changes, autoantibody specificities, and clinical course in a patient with kelch‐like protein 11 (KLHL11)‐associated paraneoplastic neurological syndrome (PNS).

Methods

Serial brain magnetic resonance images were retrospectively assessed. To test for KLHL11 autoantibodies, longitudinal cerebrospinal fluid (CSF) and serum samples were screened by Phage‐display ImmunoPrecipitation and Sequencing (PhIP‐Seq). Immunohistochemistry was also performed to assess for the presence of KLHL11 in the patient's seminoma tissue.

Results

A 42‐year‐old man presented with progressive ataxia and sensorineural hearing loss. Metastatic seminoma was detected 11 months after the onset of the neurological symptoms. Although immunotherapy was partially effective, his cerebellar ataxia gradually worsened over the next 8 years. Brain magnetic resonance imaging revealed progressive brainstem and cerebellar atrophy with a “hot‐cross‐bun sign”, and low‐signal intensity on susceptibility‐weighted imaging (SWI) in the substantia nigra, red nucleus and dentate nuclei. PhIP‐Seq enriched for KLHL11‐derived peptides in all samples. Immunohistochemical staining of mouse brain with the patient CSF showed co‐localization with a KLHL11 commercial antibody in the medulla and dentate nucleus. Immunohistochemical analysis of seminoma tissue showed anti‐KLHL11 antibody‐positive particles in cytoplasm.

Conclusions

This study suggests that KLHL11‐PNS should be included in the differential diagnosis for patients with brainstem and cerebellar atrophy and signal changes not only on T2‐FLAIR but also on SWI, which might otherwise be interpreted as secondary to a neurodegenerative disease such as multiple system atrophy.
Development and validation of the dialysis dementia risk score: A retrospective, population‐based, nested case‐control study
Authors: Ling Tsai‐Chieh , Chang Chiung‐Chih , Li Chung‐Yi , Sung Junne‐Ming , Sun Chien‐Yao , Tsai Kuen‐Jer , Cheng Ya‐Yun , Wu Jia‐Ling , Kuo Yi‐Ting , Chang Yu‐Tzu
Published: September 2021

Background

Dementia is prevalent and underdiagnosed in the dialysis population. We aimed to develop and validate a simple dialysis dementia scoring system to facilitate identification of individuals who are at high risk for dementia.

Methods

We applied a retrospective, nested case‐control study design using a national dialysis cohort derived from the National Health Insurance Research Database in Taiwan. Patients aged between 40 and 80 years were included and 2940 patients with incident dementia were matched to 29,248 non‐dementia controls. All subjects were randomly divided into the derivation and validation sets with a ratio of 4:1. Conditional logistic regression models were used to identify factors contributing to the risk score. The cutoff value of the risk score was determined by Youden's J statistic and the graphic method.

Results

The dialysis dementia risk score (DDRS) finally included age and 10 comorbidities as risk predictors. The C‐statistic of the model was 0.71 (95% confidence interval [CI] 0.70–0.72). Calibration revealed a strong linear relationship between predicted and observed dementia risk (R2 = 0.99). At a cutoff value of 50 points, the high‐risk patients had an approximately three‐fold increased risk of having dementia compared to those with low risk (odds ratio [OR] 3.03, 95% CI 2.78–3.31). The DDRS performance, including discrimination (C‐statistic 0.71, 95% CI 0.69–0.73) and calibration (p value of Hosmer−Lemeshow test for goodness of fit = 0.18), was acceptable during validation. The OR value (2.82, 95% CI 2.37–3.35) was similar to those in the derivation set.

Conclusion

The DDRS system has the potential to serve as an easily accessible screening tool to determine the high‐risk groups who deserve subsequent neurological evaluation in daily clinical practice.
Eliciting symptom‐diagnosis knowledge from online medical Q&A
Authors: Yu Ying , Huang Hao
Published: September 2021

With the objective to automatically detect diseases from symptoms in free‐text data, a methodology to extract symptom‐diagnosis knowledge from online medical textual data in Q&A domain is proposed in this paper: (1) a term frequency‐inverse document frequency and PRECISION method is adopted to retrieve symptom words from unstructured text; (2) a variable precision rough set based genetic algorithm is applied to reduce redundant symptom words, and a rough set based rule is utilized for adding discriminative symptom words assisting to discriminate diseases sharing similar symptoms; (3) by employing fuzzy linguistic variables to express the risk level of disease or severity level of symptoms, a knowledge base with fuzzy belief structure is generated. Using data extracted from a Chinese medical Q&A forum for training and testing, some classical gastrointestinal diseases serve as a case study to evaluate the efficiency of the proposed methodology. Subsequently performance comparisons are made between the proposed methodology and some other classifiers, such as the decision tree algorithms including ID3 and J45, and the Bayesian network classifier. The comparative results demonstrate that the proposed methodology outperforms the decision tree algorithms and the Bayesian network classifier.
Segmentation of malignant tumours in mammogram images: A hybrid approach using convolutional neural networks and connected component analysis
Authors: Roy Abhijit , Singh Bikesh Kumar , Banchhor Sumit K. , Verma Kesari
Published: September 2021

The segmentation of breast lesions is an important step in the computer‐aided analysis of the mammogram. The presence of noise in mammograms makes lesion detection challenging particularly for complex malignant lesions. Pre‐processing techniques can deal with the noise issue but distorts the important shape features. This motivates us to propose a novel hybrid approach by combining a convolution neural network (CNN) with connected component analysis (CCA) to segment malignant breast lesions without any pre‐processing to avoid any distortion in image sharpness at the initial stages. Two well‐known segmentation techniques namely, K‐means (KM) and Fuzzy c‐means (FCM) are also used to compare the results. From a pool of 1045 mammographic cancer images acquired from the Digital Database for Screening Mammography (DDSM), 1016 are used for training and validation, and 29 are used for testing. All three results (Hybrid, KM and FCM) are compared against the results by the expert Radiologist. The results indicate that, among various segmentation techniques, the proposed hybrid approach achieves the highest accuracy (90%), Matthew's correlation coefficient (0.79), Jaccard index (0.73) and the Dice similarity coefficient (0.84). Other performance evaluation techniques such as; precision, sensitivity, specificity, false‐positive rate, false discovery rate, negative predictive value and false‐negative rate also show the superior performance of the proposed hybrid approach. Statistical analysis (Mann–Whitney U test, T‐test, Chi‐square test, Kolmogorov–Smirnov test and Wilcoxon test), graphical analysis (Regression and Bland–Altman plots) and receiver operating characteristic curve further demonstrate the stability and consistency of the results.
Common but differentiated rights and responsibilities in tuna fisheries management
Authors: Sinan Hussain , Bailey Megan , Hanich Quentin , Azmi Kamal
Published: September 2021

The UN Law of the Sea Convention (LOSC) and one of the implementing agreements of the Convention—the UN Fish Stocks Agreement (UNFSA)—mandates all states to cooperate in the management of highly migratory and straddling fish stocks. In doing so, the UNFSA specifies that the special requirements of developing states need to be taken into account. To date, except in the Western and Central Pacific Fisheries Commission (WCPFC), there is no formal mechanism to identify these differential responsibilities in tuna regional fisheries management organizations (RFMOs). Although some conservation and management measures exempt small‐scale and artisanal fishing vessels, power imbalances within RFMOs tend to favour the interests of more developed and larger distant water fishing nations over those of small developing coastal states. To facilitate the implementation of differentiated responsibilities as mandated in UNFSA, in this study we develop a three‐step framework that could be applied in the case of new conservation and management measure proposals. The framework has also been tested based on two developing countries and compared with a developed state in the Indian Ocean Tuna Commission and the adopted resolutions in 2019. To facilitate better transparency and equitable decision‐making processes across RFMOs, this framework could be adapted based on member states' fisheries management objectives and target and non‐target species.
Reducing the Scientific Bench to Judicial Bench Research‐to‐Practice Gap: Applications of Implementation Science to Family Law Research and Practice
Authors: Rudd Brittany N. , Beidas Rinad S.
Published: September 2021

As is the case in most fields, the research‐to‐practice gap in family law is wide. The field of implementation science has emerged to attenuate these research‐to‐practice gaps. The goal of this article is to provide an overview of implementation science because drawing from efforts to reduce research‐to‐practice gaps in health care and other related fields can help the family court ameliorate its own. The current article will present an overview of implementation science, focusing specifically on how family law stakeholders can use implementation science to accelerate the implementation of evidence‐based practices, such as universal screening for intimate partner violence and the provision of parent education to divorcing parents, in their court settings. We provide practical examples and recommendations for family law practitioners seeking to implement evidence‐based practices into their settings, and we also highlight opportunities for family law researchers to integrate implementation science into future research.
How democratic is government really? The impact of subnational regime variation on evaluations of democracy
Authors: Fidalgo Amanda
Published: September 2021

Democracy is not an exclusively national concept, and subnational governments vary in respect for democratic norms and institutions. In subnational authoritarian enclaves, incumbents manipulate elections using fraud, corruption, institutional manipulation, or repression to maintain power. While we know a fair amount about how these authoritarian enclaves form and democratize, we know much less about how they affect the people that live in them. Does subnational democracy influence evaluations of democratic performance? I argue that individuals incorporate subnational outcomes into overall evaluations of democracy, and that subnational democracy positively influences these evaluations. To test this argument, I combine a new measure of subnational democracy, the Subnational Electoral Democracy Scale, with the fifth and sixth waves of the World Values Survey. I find that people living in states with high electoral democracy scores are likely to believe that elections are not manipulated, human rights are protected, and that their country is democratic.
Post‐hoc analysis on the long‐term response to fixed‐dose prophylaxis with N8‐GP in patients with haemophilia A
Authors: Tiede Andreas , Hampton Kingsley , Jiménez‐Yuste Victor , Young Guy , Benchikh el Fegoun Soraya , Chowdary Pratima
Published: September 2021

Introduction

Challenges with personalised prophylaxis in haemophilia remain, including designing unique dosing schedules that require continual adjustments and monitoring using complex sampling procedures.

Aim

To assess long‐term efficacy and pharmacokinetic outcomes with fixed‐dose N8‐GP prophylaxis.

Methods

Descriptive analyses were performed on data from the pathfinder 2 and pathfinder 5 trials of patients with severe haemophilia A. Bleed frequency and reoccurrence were assessed in relation to several clinical criteria of interest. Bleed risk relative to time since last dose was assessed using calculated annualised bleeding rate (ABR). Long‐term ABR and mean factor VIII (FVIII) trough levels were assessed in patients who received consistent N8‐GP prophylaxis every 4 days (Q4D).

Results

During pathfinder 2, 117/136 patients with study‐drug exposure of ≥600 days experienced bleeding episodes; 8.6% of bleeds were reoccurring bleeds; bleed reoccurrence decreased over time. For patients who received consistent Q4D prophylaxis across the trial (n = 61), mean ABR decreased from 3.5 bleeds/year (Year 1) to 1.6 bleeds/year (Year 6); mean FVIII trough levels stabilised at approximately 5% (Year 6). Across patients who received prophylaxis at some point during pathfinder 2 (n = 177), 125/126 (99%) reoccurring bleeds were joint bleeds. For patients receiving Q4D prophylaxis, bleeding risk generally increased as the time since the last prophylaxis dose increased. A similar reduction in ABR and stabilisation of trough level was observed in pathfinder 5.

Conclusion

Long‐term exposure (> 5 years) to fixed‐dose N8‐GP prophylaxis resulted in a protective haemostatic effect, with reduction in bleed frequency and reoccurrence, and stabilisation of FVIII trough level over time.
The prognostic significance of pleomorphism in gastrointestinal stromal tumours
Authors: Isidro Raymond A , Hornick Jason L
Published: September 2021

Aim

Gastrointestinal stromal tumours (GISTs) typically show uniform nuclear morphology, with spindle cell, epithelioid or mixed histology. Risk of progression in GIST is estimated based on anatomical site, tumour size and mitotic index. Pleomorphic GISTs are rare and have not been systematically investigated. We evaluated the prognostic significance of pleomorphism in GIST.

Methods and results

In total, 108 of 2517 (4.3%) GISTs reviewed between 2000 and 2021 were reported to show pleomorphism. Seventeen cases underwent mutational testing. Pleomorphism was noted prior to therapy in 37 GISTs, affecting 18 males and 19 females, with a mean age of 55.4 years. Most tumours arose in the stomach (n = 15) or small intestine (n = 19), with a mean size of 9.2 cm and a median mitotic rate of seven per 5 mm2; the median follow‐up was 5.7 years. Immunohistochemistry for KIT was positive in 36 (97.3%) tumours. Mutational testing revealed KIT and PDGFRA mutations in 68.4 and 21.0% of cases, respectively; no SDHX, KIT or PDGFRA alterations were found in two cases (one of which was succinate dehydrogenase‐deficient). According to standard risk assessment criteria for progressive disease, 18 tumours were high‐risk, five were moderate‐risk, four were low‐risk, five were very low‐risk and one had no risk. Disease progression was exclusive to high‐risk tumours (79%; P < 0.001).

Conclusions

Pleomorphism is present prior to therapy in approximately 2% of GISTs and is most prevalent in high‐risk gastric and small intestinal GISTs. Pleomorphism appears to have no prognostic significance beyond conventional risk stratification.
Endodontic inflammatory disease: A risk indicator for a first myocardial infarction
Authors: Sebring Dan , Buhlin Kåre , Norhammar Anna , Rydén Lars , Jonasson Peter ,   EndoReCo, Lund Henrik , Kvist Thomas
Published: September 2021

Aim

To study the association between endodontic inflammatory disease and a first myocardial infarction (MI).

Methodology

The study comprised 805 patients with recent experience of a first MI, each gender, age and geographically matched with a control. Panoramic radiographs were available for 797 patients and 796 controls. Endodontic inflammatory disease was assessed radiographically. The sum of decayed, missing and filled teeth (DMFT) was calculated, and the number of root filled teeth and teeth with periapical lesions were recorded. The associated risk of a first MI was expressed as odds ratios (OR) with 95% confidence intervals (CI), unadjusted and adjusted for confounders (family history of cardiovascular disease, smoking habits, marital status, education and diabetes).

Results

Patients who had suffered a first MI had higher DMFT (mean 22.5 vs. 21.9, p = .013) and more missing teeth (mean 7.5 vs. 6.3; p < .0001) than the healthy controls. The number of missing teeth was associated with an increased risk of a first MI (adjusted OR 1.04; CI 1.02–1.06). Conversely, decay‐free, filled teeth were associated with decreased risk (adjusted OR 0.98; CI 0.96–1.00). Analysis based on age disclosed the following variables to be associated with an increased risk of a first MI: number of decayed teeth (adjusted OR 1.18; CI 1.02–1.37, in patients <60 years), any primary periapical lesion (adjusted OR 1.57; CI 1.08–2.29, in patients <65 years) and the proportion of root filled teeth (adjusted OR 1.18; CI 1.03–1.36, in patients ≥65 years).

Conclusions

More missing teeth was independently associated with an increased risk of a first MI. In addition, endodontic inflammatory disease may contribute as an independent risk factor to cardiovascular disease since untreated caries, periapical lesions and root fillings, depending on age, were significantly associated with a first MI.
Influence of conservative endodontic access cavities on instrumentation of oval‐shaped straight root canals
Authors: dos Santos Miranda Ana Raquel Lopes , de Moura João Daniel Mendonça , Calefi Pedro Henrique Souza , Amoroso Silva Pablo Andrés , Marceliano‐Alves Marilia Fagury Videira , Lopes Ricardo Tadeu , Vivan Rodrigo Ricci , Rodrigues Patrícia de Almeida
Published: September 2021

Aim

To evaluate the influence of the design of endodontic access cavities on the percentage of unprepared areas of canal walls and flexural fatigue of instruments activated by reciprocating movement in oval‐shaped straight root canals of extracted teeth.

Methodology

Forty‐two mandibular incisors with oval canals were scanned by a microcomputed tomography (micro‐CT) device for homogeneous selection and distribution of the samples. Then, the teeth were divided into two groups (n = 21) according to the design of access cavity being tested: ultraconservative endodontic access cavity (UltraAC) and traditional access cavity. The canals were accessed with the aid of a surgical microscope, instrumented with the WaveOne Gold Medium system and irrigated with 2.5% NaOCl and 17% EDTA. The unprepared areas of the canal wall were analysed by overlaying images before and after instrumentation and expressed as percentages. micro‐CT data were analysed using t‐test, Mann–Whitney and Wilcoxon tests. The endodontic instruments used during instrumentation were subjected to static flexural fatigue testing using an artificial stainless steel canal with a 60° angle of curvature and a radius of 5 mm, located 5 mm from the tip of the instrument. The instruments were activated until fracture occurred, and the time in seconds for the fracture was recorded using a digital timer. The number of cycles to fracture was calculated and analysed statistically. For flexural fatigue data, an anova test complemented by a Tukey range test was used. The significance level of 5% was used for all analyses.

Results

There was no significant difference between the groups related to unprepared areas by the instrument during canal preparation (p > .05). The difference in flexural fatigue resistance between the groups was not significant.

Conclusion

The use of UltraAC did not interfere with the canal instrumentation of extracted mandibular incisors with straight and oval canals. There was no difference in the flexural fatigue resistance of the instruments in relation to access cavity design.
Microstructures and luminescent regulation of Ce‐doped silicate glasses with high transmittance and thermal stability
Authors: Ma Xiao , Huang Zhifeng , Yuan Hailong , Lu Xiangyu , Zhou Yujuan , Shen Qiang , Chen Fei
Published: September 2021

The traditional model for wLEDs usually encapsulates the phosphor and resin mixture on the InGaN blue‐emitting chip. However, the poor thermal stability of silicone resin will lead to the reduction of the luminescent intensity of the wLED devices. Glass has excellent thermal stability and transparency, which is a promising alternative to resins. In this work, Ce‐doped silicate luminescent glasses have been developed by a high‐temperature melting quenching method in air atmosphere. The luminescent intensity can be enhanced by increasing the heat treatment temperature and extending the heat treatment time in 10%H2/Ar atmosphere because Ce4+ ions can be reduced to Ce3+ ions. However, when the heat treatment temperature reaches 850°C, the generation of precipitates in the glass can reduce the luminescent intensity. The transmittance of glass can reach 87%, and the highest luminous intensity obtained when heat treated at 800°C. The glass transition temperature is 740°C and the thermal conductivity of the glass is .95 W m−1K−1, which is about five times higher than that of resin. The results show that the emerging Ce‐doped silicate luminescent glass could be the potential material for wLED applications.
Comparison of 12 and 24‐hours shift impacts on ICU nursing care, efficiency, safety, and work‐life quality
Authors: Koy Virya , Yunibhand Jintana , Turale Sue
Published: September 2021

Background

Nursing care quality is a central concern of health policy, and nurses’ shift schedules affect the quality of care and their work‐life status internationally. A lack of reliable information on the differences between 24‐ and 12‐h shifts on care quality, nursing care quality, patient safety, and adverse and missed events warranted investigation in Cambodia.

Aim

We aimed to examine the impacts of 12‐h shifts compared with 24‐h shifts. The purpose was to find evidence to support the use of maximum 12‐h shifts by registered nurses working in ICU contexts.

Method

A convergent mixed‐method approach was chosen to highlight the issues around the long hours of shift work. We designed a 12‐week coaching course during the implementation of 12‐h shifts and assigned 30 nurses each to an experimental group and a control group. Data from quantitative surveying of 58 participants were combined with focus group discussions of 20 participants to gather qualitative insights. Pre‐ and post‐test analysis involved descriptive statistics and the Wilcoxon sign rank test for quantitative analysis and then merged with qualitative findings from content analysis. Reporting of this study was steered by the STROBE and COREQ guidelines for quantitative and qualitative findings, respectively.

Results

Quantitative results showed the increased quality of nursing work‐life, nursing care quality, and patient satisfaction; decreased missed care and adverse events were significantly associated with the 12‐h shift. Qualitative data supported nurses preferring 12‐h rather than 24‐h shift options.

Discussion and conclusions

Changing rosters to 12‐h shifts in the intervention caused increases in the study variables’ scores. Results indicate the benefits of 12‐h shifts on the quality of nursing work‐life, nursing care quality, missed care, adverse events, and patient safety.

Implications for nursing and nursing policy

We found that 24‐h shifts had deleterious impacts on care quality and safety and nurse satisfaction with work. Health and nursing policymakers are urged to provide resources and strategize to implement 12 h shifts as soon as possible since the current 24‐h shifts of nurses affect the patient quality of care and their health and safety and that of the nurses.
Factors affecting Iranian nurses’ intention to leave or stay in the profession during the COVID‐19 pandemic
Authors: Varasteh Saeideh , Esmaeili Maryam , Mazaheri Monir
Published: September 2021

Aim

This study was conducted to explore the factors affecting nurses’ intentions to leave or stay in their profession during the coronavirus pandemic in Iran.

Introduction

Because the effectiveness of a healthcare response to a disaster depends on an available, skilled, and motivated healthcare workforce, it is essential to understand and address potential barriers to and reasons for the intentions of medical staff to leave or stay in their profession.

Methods

A qualitative study with a conventional content analysis approach was conducted. The participants included nurses working in hospitals during the COVID‐19 pandemic, and nurses who had previously left their job or had been absent from work for a period of time. The participants were selected using a purposeful sampling strategy. Data were collected through 19 in‐depth, individual semi‐structured interviews with 16 nurses. The COnsolidated criteria for REporting Qualitative research checklist was used to report the study.

Findings

Three categories; commitment and work conscience (with a subcategory of risk‐taking), fear (with two subcategories of fear of family infection and fear of protective equipment shortages), and organizational factors (with two subcategories of organizational atmosphere of the hospital and motivational factors), emerged from the analysis.

Conclusion

The reasons for quitting a nursing job or to keep working as a nurse during the pandemic include both personal and organizational factors. Commitment and work conscience in pandemic conditions is one of the main factors for keeping nurses in their profession.

Implication for nursing practice and policy

Gaining insight into nurses’ understanding of the situation and perspectives is the key to being able to provide appropriate support and keep them in the workforce. Peer support can play an important role in supporting novice nurses in facing challenges posed by a pandemic and should be improved. Also, programs and strategies need to be planned to improve resilience among nurses and to help them to manage their stress and fear.