bluuebunny/crossref_metadata_2025 huggingface dataset:
The elderly caregiver questionnaire for COVID-19 (ECQC-24)
Authors: Abdul Rahman Hanif , Bani Issa Wegdan , Rababa Mohammad , Idris Deeni Rudita , Abdul-Mumin Khadizah H. , Naing Lin
Published: May 2021

Purpose

The purpose of this paper is to introduce a new tool called the elderly caregiver questionnaire for COVID-19 (ECQC-24) that helps to assess caregiver attributes toward best possible care for elderly during this pandemic.

Design/methodology/approach

ECQC-24 was developed based on international team of experts and draw upon latest advice from reliable governing bodies such as World Health Organization and the US Centre of Disease Control. Psychometric analysis was applied to ensure the newly developed ECQC-24 is valid and reliable.

Findings

Cronbach’s alpha ranged from 0.72 to 0.87, and construct validity by exploratory factor analysis was acceptable. The results provide good estimates for the reliability and validity of ECQC-24.

Originality/value

More evidence is urgently needed to better inform clinicians, health and social policymakers and related stakeholders and organizations involved in caring for the elderly. ECQC-24, the manual to use and analyzing tools are freely available for download and use at https://sites.google.com/view/the-elderly-caregiver-covid19/home.
Propionibacterium freudenreichiithrives in microaerobic conditions by complete oxidation of lactate toCO2
Authors: Dank Alexander , van Mastrigt Oscar , Boeren Sjef , Lillevang Søren K. , Abee Tjakko , Smid Eddy J.
Published: May 2021

In this study we show increased biomass formation for four species of food‐grade propionic acid bacteria (Acidipropionibacterium acidipropionici,Acidipropionibacterium jensenii,Acidipropionibacterium thoeniiandPropionibacterium freudenreichii) when exposed to oxygen, implicating functional respiratory systems. Using an optimal microaerobic condition,P. freudenreichiiDSM 20271 consumed lactate to produce propionate and acetate initially. When lactate was depleted propionate was oxidized to acetate. We propose to name the switch from propionate production to consumption in microaerobic conditions the ‘propionate switch’. When propionate was depleted the ‘acetate switch’ occurred, resulting in complete consumption of acetate. Both growth rate on lactate (0.100 versus 0.078 h−1) and biomass yield (20.5 versus 8.6 g* mol−1lactate) increased compared to anaerobic conditions. Proteome analysis revealed that the abundance of proteins involved in the aerobic and anaerobic electron transport chains and major metabolic pathways did not significantly differ between anaerobic and microaerobic conditions. This implicates thatP.freudenreichiiis prepared for utilizing O2when it comes available in anaerobic conditions. The ecological niche of propionic acid bacteria can conceivably be extended to environments with oxygen gradients from oxic to anoxic, so‐called microoxic environments, as found in the rumen, gut and soils, where they can thrive by utilizing low concentrations of oxygen.
Travel, Expertise and Readers: Francesco Ottieri (1665–1742) and the Writing of Modern History
Authors: Beduschi Guido G.
Published: May 2021

This article analyses Francesco Ottieri's historical work, his authority as historian, and his book's eighteenth‐century readers. During the seventeenth century, books concerning recent events and early newspapers informed an expanding European readership. Between 1716 and 1735, Ottieri authored the Istoria, an eight‐volume account of the War of the Spanish Succession. Although the book circulated significantly during the eighteenth century, coming into possession of some of the period's most eminent historians, it was thereafter largely forgotten. Ottieri, a nobleman and holder of courtly offices, applied to modern history the antiquarian's new attention to sources and documents. His social status, and the experiences acquired at court and during his European travels provided both information and authority. Breaking with a late‐humanist tradition of retired statesman‐historians, Ottieri became in the reading public's eye an authoritative and impartial voice on modern history. The Istoria pioneered a new form of historiography, which combined elements of antiquarian scholarship with its author's unprecedented determination to inform the general public.
Historical change in an elite profession—Class origins and grades among law graduates over 200 years
Authors: Hansen Marianne Nordli , Strømme Thea Bertnes
Published: May 2021

This article explores the relationship between social class and educational achievement measured by grades among Norwegian law graduates over a span of 200 years. We argue that class inequalities may arise due to mechanisms favouring ‘insiders’, meaning students whose families have legal backgrounds. Alternatively, a broader category of students with origins in educated or elite families could also enjoy special advantages. Our results indicate that there were insignificant class inequalities in grades before the beginning of the 20th century, when they first appeared, and that class inequalities increased to some extent subsequently. Graduates with origins from families with legal backgrounds or origins in the cultural upper class tend to be awarded the highest grades and those with farming or working‐class origins tend to be awarded the lowest grades. Inequalities according to class origin can be explained only to a limited extent by performance at secondary school. Unlike class origin, however, the impact of grades at secondary school appears to be highly stable over time. We ask whether mechanisms favouring legal ‘insiders’ may have become less important over time, whereas the impact of cultural capital may have increased.
Resilience as a multi‐directional movement process: A conceptual and empirical exploration
Authors: Clark Janine Natalya
Published: May 2021

Movement is a recurrent thematic within extant resilience scholarship. Ecological theorizations of resilience emphasize systems that are in constant movement and flux. Terms such as “bouncing back” and “bouncing forward” are frequently used to describe how individuals recover and move on from adversity and trauma. However, integrated individual‐systemic explanations of resilience movement dynamics are lacking. Seeking to address this gap, this interdisciplinary article expressly frames resilience as a multi‐directional movement process. Individuals do not just move forward and backwards. Rather, they move in multiple and varied ways as they seek to navigate their way through adversity—and through systems and social‐ecological traps that both shape how they move and require them to keep moving. Drawing on interview data with victims‐/survivors of conflict‐related sexual violence in Bosnia‐Herzegovina (BiH), Colombia, and Uganda, the article empirically explores what “movement” looks like at the microlevel through a focus on everyday forms and expressions of movement, while also examining how wider systemic environments shape and influence these movements.
Ethnic inequality in choice‐ and performance‐driven education systems: A longitudinal study of educational choices in England, Germany, the Netherlands, and Sweden
Authors: Dollmann Jörg
Published: May 2021

The motivation for this article was the main finding of an earlier study, which concludes that choice‐driven education systems—in the study represented by England and Sweden—are particularly beneficial for immigrants in that they provide them with many opportunities to pursue their generally high educational ambitions. We extend this analysis by including two countries with performance‐driven education systems: Germany and the Netherlands. Our study specifically aims to explore whether it is true that choice‐driven systems are more beneficial for immigrants or whether immigrants can also succeed in more stratified and selective education systems. Using longitudinal data from the Children of Immigrants Longitudinal Survey in Four European Countries (CILS4EU), we show that there are no differences in (gross) transition rates between immigrants and natives in Germany, the Netherlands, and Sweden, but immigrants' optimistic choices are more pronounced in England. However, these differences diminish once we account for achievement and students' socioeconomic background in the analyses. Regarding the underlying mechanisms, we find that educational aspirations have an (equally) strong, universal impact, while anticipated discrimination plays a minor role.
Guidance on validation of lethal control measures for foodborne pathogens in foods
Authors: Ceylan Erdogan , Amezquita Alejandro , Anderson Nathan , Betts Roy , Blayo Laurence , Garces‐Vega Francisco , Gkogka Elissavet , Harris Linda J. , McClure Peter , Winkler Anett , den Besten Heidy M. W.
Published: May 2021

Food manufacturers are required to obtain scientific and technical evidence that a control measure or combination of control measures is capable of reducing a significant hazard to an acceptable level that does not pose a public health risk under normal conditions of distribution and storage. A validation study provides evidence that a control measure is capable of controlling the identified hazard under a worst‐case scenario for process and product parameters tested. It also defines the critical parameters that must be controlled, monitored, and verified during processing. This review document is intended as guidance for the food industry to support appropriate validation studies, and aims to limit methodological discrepancies in validation studies that can occur among food safety professionals, consultants, and third‐party laboratories. The document describes product and process factors that are essential when designing a validation study, and gives selection criteria for identifying an appropriate target pathogen or surrogate organism for a food product and process validation. Guidance is provided for approaches to evaluate available microbiological data for the target pathogen or surrogate organism in the product type of interest that can serve as part of the weight of evidence to support a validation study. The document intends to help food manufacturers, processors, and food safety professionals to better understand, plan, and perform validation studies by offering an overview of the choices and key technical elements of a validation plan, the necessary preparations including assembling the validation team and establishing prerequisite programs, and the elements of a validation report.
New insights into hydroxyectoine synthesis and its transcriptional regulation in the broad‐salt growing halophilic bacteriumChromohalobacter salexigens
Authors: Argandoña Montserrat , Piubeli Francine , Reina‐Bueno Mercedes , Nieto Joaquín J. , Vargas Carmen
Published: May 2021

Elucidating the mechanisms controlling the synthesis of hydroxyectoine is important to design novel genetic engineering strategies for optimizing the production of this biotechnologically relevant compatible solute. The genome of the halophilic bacteriumChromohalobacter salexigenscarries two ectoine hydroxylase genes, namelyectDandectE, whose encoded proteins share the characteristic consensus motif of ectoine hydroxylases but showed only a 51.9% identity between them. In this work, we have shown thatectEencodes a secondary functional ectoine hydroxylase and that the hydroxyectoine synthesis mediated by this enzyme contributes toC.␣salexigensthermoprotection. The evolutionary pattern of EctD and EctE and related proteins suggests that they may have arisen from duplication of an ancestral gene preceding the directional divergence that gave origin to the orders Oceanospirillales and Alteromonadales. Osmoregulated expression ofectDat exponential phase, as well as the thermoregulated expression ofectDat the stationary phase, seemed to be dependent on the general stress factor RpoS. In contrast, expression ofectEwas always RpoS‐dependent regardless of the growth phase and osmotic or heat stress conditions tested. The data presented here suggest that the AraC‐GlxA‐like EctZ transcriptional regulator, whose encoding gene lies upstream ofectD, plays a dual function under exponential growth as both a transcriptional activator of osmoregulatedectDexpression and a repressor ofectEtranscription, privileging the synthesis of the main ectoine hydroxylase EctD. Inactivation ofectZresulted in a higher amount of the total ectoines pool at the expenses of a higher accumulation of ectoine, with maintenance of the hydroxyectoine levels. In addition to the transcriptional control, our results suggest a strong post‐transcriptional regulation of hydroxyectoine synthesis. Data on the accumulation of ectoine and hydroxyectoine inrpoSandectZstrains pave the way for using these genetic backgrounds for metabolic engineering for hydroxyectoine production.
Convergent phenotypic evolution towards fosfomycin collateral sensitivity of Pseudomonas aeruginosa antibiotic‐resistant mutants
Authors: Laborda Pablo , Martínez José L. , Hernando‐Amado Sara
Published: May 2021

The rise of antibiotic resistance and the reduced amount of novel antibiotics support the need of developing novel strategies to fight infections, based on improving the use of the antibiotics we already have. Collateral sensitivity is an evolutionary trade‐off associated with the acquisition of antibiotic resistance that can be exploited to tackle this relevant health problem. However, different works have shown that patterns of collateral sensitivity are not always conserved, thus precluding the exploitation of this evolutionary trade‐off to fight infections. In this work, we identify a robust pattern of collateral sensitivity to fosfomycin in Pseudomonas aeruginosa antibiotic‐resistant mutants, selected by antibiotics belonging to different structural families. We characterize the underlying mechanism of the collateral sensitivity observed, which is a reduced expression of the genes encoding the peptidoglycan‐recycling pathway, which preserves the peptidoglycan synthesis in situations where its de novo synthesis is blocked, and a reduced expression of fosA, encoding a fosfomycin‐inactivating enzyme. We propose that the identification of robust collateral sensitivity patterns, as well as the understanding of the molecular mechanisms behind these phenotypes, would provide valuable information to design evolution‐based strategies to treat bacterial infections.
Programming living sensors for environment, health and biomanufacturing
Authors: Wan Xinyi , Saltepe Behide , Yu Luyang , Wang Baojun
Published: May 2021

Synthetic biology offers new tools and capabilities of engineering cells with desired functions for example as new biosensing platforms leveraging engineered microbes. In the last two decades, bacterial cells have been programmed to sense and respond to various input cues for versatile purposes including environmental monitoring, disease diagnosis and adaptive biomanufacturing. Despite demonstrated proof‐of‐concept success in the laboratory, the real‐world applications of microbial sensors have been restricted due to certain technical and societal limitations. Yet, most limitations can be addressed by new technological developments in synthetic biology such as circuit design, biocontainment and machine learning. Here, we summarize the latest advances in synthetic biology and discuss how they could accelerate the development, enhance the performance and address the present limitations of microbial sensors to facilitate their use in the field. We view that programmable living sensors are promising sensing platforms to achieve sustainable, affordable and easy‐to‐use on‐site detection in diverse settings.
Acceleration of ageing via disturbing mTOR‐regulated proteostasis by a new ageing‐associated gene PC4
Authors: Chen Long , Liao Fengying , Wu Jie , Wang Ziwen , Jiang Zhongyong , Zhang Chi , Luo Peng , Ma Le , Gong Qiang , Wang Yang , Wang Qing , Luo Min , Yang Zeyu , Han Shiqian , Shi Chunmeng
Published: May 2021

Research on ageing‐associated genes is important for investigating ageing and anti‐ageing strategies. Here, we firstly reported that the human positive cofactor 4 (PC4), a multifunctional and highly conserved nucleoprotein, is accumulated and activated during ageing and causes global accelerated ageing process by disrupting proteostasis. Mechanistically, PC4 interacts with Sin3‐HDAC complex and inhibits its deacetylated activity, leads to hyper‐acetylation of the histones at the promoters of mTOR‐related genes and causes mTOR signalling activation. Accordingly, mTOR activation causes excessive protein synthesis, resulting in impaired proteostasis and accelerated senescence. These results reveal a new biological function of PC4 in vivo, recognizes PC4 as a new ageing‐associated gene and provides a genetically engineered mouse model to simulate natural ageing. More importantly, our findings also indicate that PC4 is involved in histone acetylation and serves as a potential target to improve proteostasis and delay ageing.
Racial and ethnic disparities in bronchiolitis management in freestanding children's hospitals
Authors: Honcoop Aubree C. , Poitevien Patricia , Kerns Ellen , Alverson Brian , McCulloh Russell J.
Published: May 2021

Objective

Variation in bronchiolitis management by race and ethnicity within emergency departments (EDs) has been described in single‐center and prospective studies, but large‐scale assessments across EDs and inpatient settings are lacking. Our objective is to describe the association between race and ethnicity and bronchiolitis management across 37 U.S. freestanding children's hospitals from 2015 to 2018.

Methods

Using the Pediatric Health Information System, we analyzed ED and inpatient visits from November 2015 to November 2018 of children with bronchiolitis 3 to 24 months old. Rates of use for specific diagnostic tests and therapeutic measures were compared across the following race/ethnicity categories: 1) non‐Hispanic White (NHW), 2) non‐Hispanic Black (NHB), 3) Hispanic, and 4) other. The subanalyses of ED patients only and children < 1 year old were performed. Mixed‐effect logistic regression was performed to compare the adjusted odds of receiving specific test/treatment using NHW children as the reference group.

Results

A total of 134,487 patients met inclusion criteria (59% male, 28% NHB, 26% Hispanic). Adjusted analysis showed that NHB children had higher odds of receiving medication associated with asthma (odds ratio [OR] = 1.27, 95% confidence interval [CI] = 1.22 to 1.32) and lower odds of receiving diagnostic tests (blood cultures, complete blood counts, viral testing, chest x‐rays; OR = 0.78, 95% CI = 0.75 to 0.81) and antibiotics (OR = 0.58, 95% CI = 0.52 to 0.64) than NHW children. Hispanic children had lower odds of receiving diagnostic testing (OR = 0.94, 95% CI = 0.90 to 0.98), asthma‐associated medication (OR = 0.92, 95% CI = 0.88 to 0.96), and antibiotics (OR = 0.74, 95% CI = 0.66 to 0.82) compared to NHW children.

Conclusion

NHB children more often receive corticosteroid and bronchodilator therapies; NHW children more often receive antibiotics and chest radiography. Given that current guidelines generally recommend supportive care with limited diagnostic testing and medical intervention, these findings among NHB and NHW children represent differing patterns of overtreatment. The underlying causes of these patterns require further investigation.
KCNK13 potassium channels in the ventral tegmental area of rats are important for excitation of ventral tegmental area neurons by ethanol
Authors: You Chang , Vandegrift Bertha J. , Brodie Mark S.
Published: May 2021

Background

Alcohol excites neurons of the ventral tegmental area (VTA) and the release of dopamine from these neurons is a key event in ethanol (EtOH)‐induced reward and reinforcement. Many mechanisms have been proposed to explain EtOH's actions on neurons of the VTA, but antagonists generally do not eliminate the EtOH‐induced excitation of VTA neurons. We have previously demonstrated that the ion channel KCNK13 plays an important role in the EtOH‐related excitation of mouse VTA neurons. Here, we elaborate on that finding and further assess the importance of KCNK13 in rats.

Methods

Rats (Sprague–Dawley and Fisher 344) were used in these studies. In addition to single‐unit electrophysiology in brain slices, we used quantitative PCR and immunohistochemistry to discern the effects of EtOH and the brain slice preparation method on the expression levels of the Kcnk13 gene and KCNK13 protein.

Results

Immunohistochemistry demonstrated that the levels of KCNK13 were significantly reduced during procedures normally used to prepare brain slices for electrophysiology, with a reduction of about 75% in KCNK13 protein at the time that electrophysiological recordings would normally be made. Extracellular recordings demonstrated that EtOH‐induced excitation of VTA neurons was reduced after knockdown of Kcnk13 using a small interfering RNA (siRNA) delivered via the recording micropipette. Real‐time PCR demonstrated that the expression of Kcnk13 was altered in a time‐dependent manner after alcohol withdrawal.

Conclusions

KCNK13 plays an important role in EtOH‐induced stimulation of rat VTA neurons and is dynamically regulated by cell damage and EtOH exposure, and during withdrawal. KCNK13 is a novel alcohol‐sensitive protein, and further investigation of this channel may offer new avenues for the development of agents useful in altering the rewarding effect of alcohol.
COVID‐19 impact, sustainability performance and firm value: international evidence
Authors: Bose Sudipta , Shams Syed , Ali Muhammad Jahangir , Mihret Dessalegn
Published: May 2021

We examine the impact of COVID‐19 on changes in firm value, and the moderating role of firm‐level sustainability performance on this relationship. We find that firms domiciled in countries where the COVID‐19 impact is more devastating experienced greater decline in firm value. The negative impact of COVID‐19 on firm value is less pronounced for firms with better sustainability performance. Firms domiciled in countries with higher levels of environmental‐ and stakeholder‐value‐oriented culture experienced less decline in firm value from the impact of COVID‐19. Findings suggest a firm’s stakeholder‐value orientation contributes to preserving a firm’s value when general stakeholder value declines.
The Impact of Protecting EU Geographical Indications in Trade Agreements
Authors: Curzi Daniele , Huysmans Martijn
Published: May 2021

The European Union protects over 1,000 Geographical Indications for distinctive regional foods such as Parma ham and Feta cheese. This paper tests whether external protection of Geographical Indications through trade agreements has increased exports of European Union Geographical Indications. The answer matters for trade policy, because the protection of at least some Geographical Indications has been a red line in recent trade negotiations. We use detailed export data for cheeses, covering the 2004–2019 period. The analysis uses the latest trade models that take into account the possibility of zero‐trade flows for certain goods. We find that legal protection of Geographical Indications in trade agreements does not generally lead to significant additional exports above and beyond the general export‐promoting effects of trade agreements. This finding should limit international fears of protected Geographical Indications widely displacing comparable products made outside of the European Union. However, although there is no significant effect across the board, more detailed analyses do find significant effects. In particular, Geographical Indications of higher quality and with higher market shares do benefit from stronger external legal protection. Based on these findings, the European Union may want to refocus its demands for protection of Geographical Indications during trade negotiations.
The penile duplex ultrasound: How and when to perform it?
Authors: Aversa Antonio , Crafa Andrea , Greco Emanuela Alessandra , Chiefari Eusebio , Brunetti Antonio , La Vignera Sandro
Published: May 2021

Background

Because it is a superficial structure, the penis is ideally suited to ultrasound imaging. A number of disease processes, including Peyronie's disease, penile fractures and tumors, are clearly visualized with ultrasound. Baseline and dynamic assessment of cavernosal arterial changes after pharmaco‐stimulation with alprostadil allows standardized diagnosis of arterial and venogenic causes of erectile dysfunction (ED).

Objective

To illustrate how to correctly perform flaccid and dynamic penile duplex ultrasound (D‐PDU) and in which patients to recommend it.

Materials/Methods

An extensive search of the literature was carried out on Pubmed with the insertion of the following Medical Subjects Headings (MeSH) terms and keywords “penile color Doppler ultrasound” “peak systolic velocity” “end‐diastolic velocity”, “acceleration time”, “resistance index”.

Evidence

In our experience, arterial erectile dysfunction is identified after standardized intracavernous injection (ICI) of alprostadil (10 mcg) when values of peak systolic velocity (PSV) are <35 cm/s and, in the most severe forms, for values <25 cm/s. Arterial insufficiency can also be identified by increased acceleration time (AT) values (>110 ms) and/or by a lack of visualization of helicine arteries at power Doppler mode along with incomplete achievement of penile rigidity. The veno‐occlusive incompetence is determined when end‐diastolic velocity (EDV) values are >4.5–5 cm/s or in the case of resistance index (RI) values <0.75. The assessment of additional surrogate markers of endothelial dysfunction, that is, intima‐media thickness, mean platelet volume (MPV), endothelial progenitor cells (EPC), endothelial cell specific molecule‐1(endocan) are also useful in assessing the patient's cardiovascular risk but are still considered investigational in the interpretation of D‐PDU results.

Conclusion

D‐PDU scan after ICI with vasoactive drugs is a safe procedure and represents the gold standard for the diagnostics of penile pathologies and should be performed in men with ED not responding to oral conventional therapies and/or in those requiring accurate stratification of cardiovascular risk.
Postpubertal spermatogonial stem cell transplantation restores functional sperm production in rhesus monkeys irradiated before and after puberty
Authors: Shetty Gunapala , Mitchell Jennifer M. , Lam Truong N. A. , Phan Thien T. , Zhang Jie , Tailor Ramesh C. , Peters Karen A. , Penedo Maria Cecilia , Hanna Carol B. , Clark Amander T. , Orwig Kyle E. , Meistrich Marvin L.
Published: May 2021

Background

Cancer treatment of prepubertal patients impacts future fertility due to the abolition of spermatogonial stem cells (SSCs). In macaques, spermatogenesis could be regenerated by intratesticular transplantation of SSCs, but no studies have involved cytotoxic treatment before puberty and transplantation after puberty, which would be the most likely clinical scenario.

Objectives

To evaluate donor‐derived functional sperm production after SSC transplantation to adult monkeys that had received testicular irradiation during the prepubertal period.

Materials and methods

We obtained prepubertal testis tissue by unilaterally castrating six prepubertal monkeys and 2 weeks later irradiated the remaining testes with 6.9 Gy. However, because spermatogenic recovery was observed, we irradiated them again 14 months later with 7 Gy. Three of the monkeys were treated with GnRH‐antagonist (GnRH‐ant) for 8 weeks. The cryopreserved testis cells from the castrated testes were then allogeneically transplanted into the intact testes of all monkeys. Tissues were harvested 10 months later for analyses.

Results

In three of the six monkeys, 61%, 38%, and 11% of the epididymal sperm DNA were of the donor genotype. The ability to recover donor‐derived sperm production was not enhanced by the GnRH‐ant pretreatment. However, the extent of filling seminiferous tubules during the transplantation procedure was correlated with the eventual production of donor spermatozoa. The donor epididymal spermatozoa from the recipient with 61% donor contribution were capable of fertilizing rhesus eggs and forming embryos. Although the transplantation was done into the rete testis, two GnRH‐ant‐treated monkeys, which did not produce donor‐derived epididymal spermatozoa, displayed irregular tubular cords in the interstitium containing testicular spermatozoa derived from the transplanted donor cells.

Discussion and Conclusion

The results further support that sperm production can be restored in non‐human primates from tissues cryopreserved prior to prepubertal and post‐pubertal gonadotoxic treatment by transplantation of these testicular cells after puberty into seminiferous tubules.
Chekhov’s gun and Narrative Topography in Social Science Texts
Authors: Lund Christian
Published: May 2021

A social science text has topography. Idea, concepts, and data are structured in a narrative form and the writer faces three challenges: 1) how to deal with the complexity of knowledge in a linear form of writing, 2) how to transform experience and the wealth of data you needed to know to write, into focused and lean writing that the reader needs to read, and finally 3) how, while providing a synthetic representation of reality, to establish memorable credibility of the data and narrative. These challenges can be addressed and overcome by the use of devices we can identify most clearly in art.
Model‐based inference using judgement post‐stratified samples in finite populations
Authors: Ozturk Omer , Kavlak Konul Bayramoglu
Published: May 2021

In survey sampling studies, statistical inference can be constructed either using design based randomisation or super population model. Design‐based inference using judgement post‐stratified (JPS) sampling is available in the literature. This paper develops statistical inference based on super population model in a finite population setting using JPS sampling design. For a JPS sample, first a simple random sample (SRS) is constructed without replacement. The sample units in this SRS are then stratified based on judgement ranking in a small comparison set to induce a data structure in the sample. The paper shows that the mean of a JPS sample is model unbiased and has smaller mean square prediction error (MSPE) than the MSPE of a simple random sample mean. Using an unbiased estimator of the MSPE, the paper also constructs prediction confidence interval for the population mean. A small‐scale empirical study shows that the JPS sample predictor performs better than an SRS predictor when the quality of ranking information in JPS sampling is not poor. The paper also shows that the coverage probabilities of prediction intervals are very close to the nominal coverage probability. Proposed inferential procedure is applied to a real data set obtained from an agricultural research farm.
Classification of archaeological adhesives from Eastern Europe and Urals by ATR‐FT‐IR spectroscopy and chemometric analysis
Authors: Chen Shidong , Vahur Signe , Teearu Anu , Juus Taisi , Zhilin Mikhail , Savchenko Svetlana , Oshibkina Svetlana , Asheichyk Vitali , Vashanau Aliaksandr , Lychagina Evgeniia , Kashina Ekaterina , German Konstantin , Dubovtseva Ekaterina , Kriiska Aivar , Leito Ivo , Oras Ester
Published: May 2021

Attenuated total reflection‐Fourier transform‐infrared spectroscopy (ATR‐FT‐IR) analysis of 100 adhesive samples from different prehistoric composite artefacts, pottery, and amorphous lumps across Eastern Europe and Urals were conducted with the aim to establish a fast analytical screening method for adhesive assignment. The ATR‐FT‐IR analysis allowed the identification of major chemical components of the adhesive samples that were assigned to three main groups: birch bark tar without major additives, birch bark tar with additives, and minor/non‐birch bark tar samples. ATR‐FT‐IR spectra were further analyzed using principal component analysis (PCA)‐based discriminant analysis (DA) that allowed additional refinement of adhesive classifications. The ATR‐FT‐IR results and the DA classification were confirmed by analyzing a selection of samples with gas chromatography–mass spectrometry (GC–MS). Results demonstrate that ATR‐FT‐IR coupled with DA classification allows fast and reliable preliminary identification of the major components in archaeological adhesives and their further classification. As such it is a considerable and faster alternative to more laborious GC–MS analysis, especially in the case of very small samples.
A mean weight analysis of Classic Nabatean lamp sherds from Roman Aila (Aqaba, Jordan)
Authors: Lapp Eric C.
Published: May 2021

A mean weight analysis was conducted on Classic Nabatean type lamp sherds (N = 75) unearthed at the Red Sea port of Roman Aila (Aqaba, Jordan). The purpose of this essay is to independently test and replicate Diedre Barrett's mean weight methodology to verify its viability as a procedure to determine the estimated original complete lamp count for this group at the site. The study further suggests modifications to the analysis and proposes an equation to express the mean weight procedure.
Paying the widening participation penalty: Racial and ethnic minority students and mental health in British universities
Authors: Olaniyan Funmi‐Victoria
Published: May 2021

Racial and ethnic minority (REM) students are more likely to experience poor mental health than their White peers yet are less likely to seek help from university counseling services. In attempting to explain this puzzle, the role of environmental factors are rarely explored, despite evidence which suggests that the university environment is itself a major factor. Here, I take a qualitative paired comparison approach to examine the influence of the university environment on the mental health and help‐seeking attitudes of REM undergraduate students, evaluating their experiences at a Russell Group university (RGU) with low REM participation and a neighboring non‐Russell Group university with high REM participation. While both universities declared a commitment to widen participation and promote inclusion for REM individuals, semi‐structured interviews with 48 REM students reveal that feelings of isolation and the experience of discrimination were heightened at the RGU. However, students at both universities described having to navigate a “minefield” of racial microaggressions and “othering.” Further, these environmental pressures are compounded by personal factors (i.e., prior help‐seeking experiences, cultural norms, and family pressures). Together, these factors largely influence both their mental health and their help‐seeking attitudes. I argue that these factors create a widening participation penalty for REM students and suggest that support for these students must go beyond initial acts of increasing diversity on campus (for example, through Widening Participation schemes). Rather, efforts should focus on addressing and reforming the institutional environments and behaviors that hinder university campuses from becoming truly inclusive and mentally healthy environments.
Oral paclitaxel with encequidar compared to intravenous paclitaxel in patients with advanced cancer: A randomised crossover pharmacokinetic study
Authors: Jackson Christopher G. C. A. , Hung Tak , Segelov Eva , Barlow Paula , Prenen Hans , McLaren Blair , Hung Noelyn Anne , Clarke Katriona , Chao Tsu‐Yi , Dai Ming‐Shen , Yeh Hsien‐Tang , Cutler David L. , Kramer Douglas , He Jimmy , Zhi Jay , Chan Wing‐Kai , Kwan Rudolf , Deva Sanjeev
Published: May 2021

Aims

Paclitaxel is a widely used anti‐neoplastic agent but has low oral bioavailability due to gut extrusion by P‐glycoprotein (P‐gp). Oral paclitaxel could be more convenient, less resource intensive, and more tolerable than intravenous administration. Encequidar (HM30181A) is a novel, minimally absorbed gut‐specific P‐gp inhibitor. We tested whether administration of oral paclitaxel with encequidar (oPac+E) achieved comparable AUC to intravenous paclitaxel (IVP) 80 mg/m2.

Methods

We conducted a multi‐centre randomised crossover study with two treatment periods. Patients (pts) with advanced cancer received either oral paclitaxel 615 mg/m2 divided over 3 days and encequidar 15 mg orally 1 hour prior, followed by IVP 80 mg/m2, or the reverse sequence. PK blood samples were taken up to Day 9 for oPac+E and Day 5 for IVP.

Results

Forty‐two patients were enrolled; 35 completed both treatment periods. AUC0‐∞was 5033.5 ± 1401.1 ng.h/mL for oPac+E and 5595.9 ± 1264.1 ng.h/mL with IVP. The geometric mean ratio (GMR) for AUC was 89.50% (90% CI 83.89–95.50). Mean absolute bioavailability of oPac+E was 12% (CV% = 23%). PK parameters did not change meaningfully after 4 weeks administration of oPac+E in an extension study. G3 treatment‐emergent adverse events occurred in seven (18%) pts with oPac+E and two (5%) with IVP. Seventy‐five per cent of patients preferred oPac+E over IVP.

Conclusions

GMR for AUC was within the predefined acceptable range of 80–125% for demonstrating equivalence. oPac+E is tolerable and there is no evidence of P‐gp induction with repeat administration. With further study, oPac+E could be an alternative to IVP.
Macrophage extracellular traps aggravate iron overload‐related liver ischaemia/reperfusion injury
Authors: Wu Shan , Yang Jing , Sun Guoliang , Hu Jingping , Zhang Qian , Cai Jun , Yuan Dongdong , Li Haobo , Hei Ziqing , Yao Weifeng
Published: May 2021

Background and Purpose

Macrophages regulate iron homeostasis in the liver and play important role in hepatic ischaemia/reperfusion (I/R) injury. This study investigates the role of macrophages in iron overload‐related hepatocyte damage during liver I/R.

Experimental Approach

Liver biopsies from patients undergoing partial hepatectomy with or without hepatic portal occlusion were recruited and markers of hepatocyte cell death and macrophage extracellular traps (METs) were detected. A murine hepatic I/R model was also established in high‐iron diet‐fed mice. Ferrostatin‐1 and deferoxamine were administered to investigate the role of ferroptosis in hepatic I/R injury. The macrophage inhibitor liposome‐encapsulated clodronate was used to investigate the interaction between macrophages and ferroptosis. AML12 hepatocytes and RAW264.7 macrophages were co‐cultured in vitro. An inhibitor of macrophage extracellular traps was used to evaluate the role and mechanism of these traps and ferroptosis in hepatic I/R injury.

Key Results

Hepatocyte macrophage extracellular trap formation and ferroptosis were greater in patients who underwent hepatectomy with hepatic portal occlusion and in mice subjected to hepatic I/R. Macrophage extracellular traps increased when macrophages were subjected to hypoxia/reoxygenation and when they were co‐cultured with hepatocytes. Ferroptosis increased and post‐hypoxic hepatocyte survival decreased, which were reversed by inhibition of macrophage extracellular traps. Ferroptosis inhibition attenuated post‐ischaemic liver damage. Moreover, iron overload induced hepatic ferroptosis and exacerbated post‐ischaemic liver damage, which were reversed by the iron chelator.

Conclusion and Implications

Macrophage extracellular traps are in volved in regulating ferroptosis highlighting the therapeutic potential of macrophage extracellular traps and ferroptosis inhibition in reducing liver I/R injury.
Sexual conflict in a changing environment
Authors: Plesnar‐Bielak Agata , Łukasiewicz Aleksandra
Published: May 2021

Sexual conflict has extremely important consequences for various evolutionary processes including its effect on local adaptation and extinction probability during environmental change. The awareness that the intensity and dynamics of sexual conflict is highly dependent on the ecological setting of a population has grown in recent years, but much work is yet to be done. Here, we review progress in our understanding of the ecology of sexual conflict and how the environmental sensitivity of such conflict feeds back into population adaptivity and demography, which, in turn, determine a population's chances of surviving a sudden environmental change. We link two possible forms of sexual conflict – intralocus and interlocus sexual conflict – in an environmental context and identify major gaps in our knowledge. These include sexual conflict responses to fluctuating and oscillating environmental changes and its influence on the interplay between interlocus and intralocus sexual conflict, among others. We also highlight the need to move our investigations into more natural settings and to investigate sexual conflict dynamics in wild populations.
The IDIP framework for assessing protein function and its application to the prion protein
Authors: Schmitt‐Ulms Gerold , Mehrabian Mohadeseh , Williams Declan , Ehsani Sepehr
Published: May 2021

The quest to determine the function of a protein can represent a profound challenge. Although this task is the mandate of countless research groups, a general framework for how it can be approached is conspicuously lacking. Moreover, even expectations for when the function of a protein can be considered to be ‘known’ are not well defined. In this review, we begin by introducing concepts pertinent to the challenge of protein function assignments. We then propose a framework for inferring a protein's function from four data categories: ‘inheritance’, ‘distribution’, ‘interactions’ and ‘phenotypes’ (IDIP). We document that the functions of proteins emerge at the intersection of inferences drawn from these data categories and emphasise the benefit of considering them in an evolutionary context. We then apply this approach to the cellular prion protein (PrPC), well known for its central role in prion diseases, whose function continues to be considered elusive by many investigators. We document that available data converge on the conclusion that the function of the prion protein is to control a critical post‐translational modification of the neural cell adhesion molecule in the context of epithelial‐to‐mesenchymal transition and related plasticity programmes. Finally, we argue that this proposed function of PrPC has already passed the test of time and is concordant with the IDIP framework in a way that other functions considered for this protein fail to achieve. We anticipate that the IDIP framework and the concepts analysed herein will aid the investigation of other proteins whose primary functional assignments have thus far been intractable.
Fine‐Tuning the “Right to Rio de Janeiro” from Above and Below: The City Statute in Pre‐Olympics Rio de Janeiro
Authors: Svoboda Kayla
Published: May 2021

Brazil’s City Statute enshrines the “right to the city” and the “social function of property” in its constitution. Brazilian scholars, however, identify barriers to achieving the law’s agenda. Broader debates regarding the right to the city suggest the concept has been overextended beyond meaning, and that formalization of the right to the city betrays its radical Lefebvrian roots. This article is based on fieldwork conducted in Rio de Janeiro when widespread forced evictions were being carried out prior to the city’s hosting of the 2016 Summer Olympics. Based on observations within eleven housing occupations, and sixty interviews with participants, leaders of social movement organizations, and local politicians, the article argues that the “constitutionalization” of the right to the city and the social function of property formed the basis for the politicization of dispossessed urban residents. The social function of property was a particularly salient concept for capturing the injustice of the planned relocation of the displaced poor to the urban periphery, while countless buildings sat underutilized in the city center.
Impact of beta‐2 microglobulin expression on the survival of glioma patients via modulating the tumor immune microenvironment
Authors: Tang Feng , Zhao Yu‐Hang , Zhang Qing , Wei Wei , Tian Su‐Fang , Li Chen , Yao Jie , Wang Ze‐Fen , Li Zhi‐Qiang
Published: May 2021

Aims

High immune cell infiltration in gliomas establishes an immunosuppressive tumor microenvironment, which in turn promotes resistance to immunotherapy. Hence, it is important to identify novel targets associated with high immune cell infiltration in gliomas. Our previous study showed that serum levels of beta‐2 microglobulin (B2M) in lower‐grade glioma patients were lower than those in glioblastoma patients. In the present study, we focused on exploring the roles of B2M in glioma immune infiltration.

Methods

A large cohort of patients with gliomas from the TCGA, CGGA, and Gravendeel databases was included to explore differential expression patterns and potential roles of B2M in gliomas. A total of 103 glioma tissue samples were collected to determine the distributions of B2M protein levels by immunofluorescent assays. Kaplan‐Meier survival analysis and meta‐analysis were used for survival analysis. GO(Gene‐ontology) enrichment analysis, co‐expression analysis, KEGG(Kyoto Encyclopedia of Genes and Genomes) pathway analysis, and immune infiltration analysis were performed to explore roles and related mechanisms of B2M in glioma.

Results

We found that both B2M mRNA and protein levels were abnormally upregulated in glioma samples compared with those from normal brain tissue. B2M expression was correlated with tumor grade and was downregulated in IDH1 mutant samples. Furthermore, B2M was a moderately sensitive indicator for predicting the mesenchymal molecular subtype of gliomas. Interestingly, glioma patients with lower B2M expression had remarkably longer survival times than those with higher B2M expression. Moreover, meta‐analysis showed that B2M was an independent predictive marker in glioma patients. The results of GO enrichment analysis revealed that B2M contributed to immune cell infiltration in glioma patients. In addition, results of KEGG pathway analysis and co‐expression analysis suggested that B2M may mediate glioma immune infiltration via chemokines.

Conclusions

We conclude that B2M levels are critical for the survival times of glioma patients, at least in part due to mediating high immune infiltration.
Drinking and acquisition of unrecorded alcohol across educational groups in Sweden
Authors: Norström Thor , Landberg Jonas , Trolldal Björn
Published: May 2021

Introduction

It is estimated that 18.5% of total alcohol consumption in Sweden in 2018 was unrecorded. However, little is known about the socio‐economic profile of consumers of unrecorded alcohol. The aim of this study was to elucidate this issue by analysing data from a unique Swedish national repeated cross‐sectional alcohol use survey.

Methods

Individual‐level information on alcohol consumption and socio‐economic status (SES) for the years 2013–2018 was retrieved from the Monitoring Project; a nationally representative monthly alcohol use survey. The analytical sample comprised 64 375 respondents aged 25–74 years. SES was measured by educational level. We used three educational groups: (i) low (<10 years); (ii) intermediate (10–12 years); and (iii) high (13+ years). We included indicators of the following sources of unrecorded alcohol consumption: travellers' import, smuggled alcohol, home production, internet and illicit home‐distilling. We estimated adjusted SES‐specific means of the various forms of unrecorded consumption. The means were adjusted for the effects of age, sex and region.

Results

There were no significant educational differences in the total of unrecorded alcohol consumption; the same holds true for home‐production and internet. However, with respect to smuggled and home‐distilling, a statistically significant educational gradient was observed with the lowest educational group scoring approximately four times higher than the highest.

Discussion and Conclusions

Our findings suggest that there are no differences across educational groups in the consumption of unrecorded alcohol as a whole. However, consumption of smuggled alcohol and illicitly distilled spirits is elevated in the low educational group.