Great Britain Research Articles

Interaction of the tumor suppressor SMAD4 and WNT signaling in progression to oral squamous cell carcinoma.

SMAD4 is a tumor suppressor mutated or silenced in multiple cancers, including oral cavity squamous cell carcinoma (OSCC). Human clinical samples and cell lines, mouse models and organoid culture were used to investigate the role that SMAD4 plays in progression from benign disease to invasive OSCC. Human OSCC lost detectable SMAD4 protein within tumor epithelium in 24% of cases, and this loss correlated with worse progression-free survival independent of other major clinical and pathological features. A mouse model engineered for KrasG12D expression in the adult oral epithelium induced benign papillomas, however the combination of KrasG12D with loss of epithelial Smad4 expression resulted in rapid development of invasive carcinoma with features of human OSCC. Examination of regulatory pathways in 3D organoid cultures of SMAD4+ and SMAD4- mouse tumors with Kras mutation found that either loss of SMAD4 or inhibition of TGFβ signaling upregulated the WNT pathway and altered the extracellular matrix. The gene signature of the mouse tumor organoids lacking SMAD4 was highly similar to the gene signature of human head and neck squamous cell carcinoma. In summary, this work has uncovered novel mechanisms by which SMAD4 acts as a tumor suppressor in OSCC. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Measuring Expenditure with a Mobile App: Do Probability-Based and Nonprobability Panels Differ?

Abstract In this case study, we examine a novel aspect of data collected in a typical probability and a typical nonprobability panel: mobile app data. The data were collected in Great Britain in 2018, using the Innovation Panel of the UK Household Longitudinal Study and the Lightspeed online access panel. Respondents in each panel were invited to participate in a month-long study, reporting all their daily expenditures in the app. In line with most of the research on nonprobability and probability-based panel data, our results indicate differences in the data gathered from these data sources. For example, more female, middle-aged, and highly educated people with higher digital skills and a greater interest in their finances participated in the nonprobability app study. Our findings also show that resulting differences in the app spending data are difficult to eliminate by weighting. The only data quality aspect for which we do not find evidence of differences between the nonprobability and probability-based panel is behavior in using the spending app. This finding is contrary to the argument that nonprobability online panel participants try to maximize their monetary incentive at the expense of data quality. However, this finding is in line with some of the scarce existing literature on response behavior in surveys, which is inconclusive regarding the question of whether nonprobability online panel participants answer questions less conscientiously than probability-based panel respondents. Since the two panels in our case study differ in more aspects than the sample selection procedure, more research in different contexts is necessary to establish generalizability and causality.

STRUCTURAL AND SEMANTIC FEATURES OF BRITISH TOPONYMS

The article is devoted to the review of structural and semantic features of British toponyms. The study of toponyms helps to understand the linguistic image of the world, highlighting ethnic experience and culture. Toponyms are important as means of transmitting historical, cultural, and other information across generations, which makes their study relevant in linguistics. The proper names of British territories are very diverse, as the country has been home to various civilizations and peoples for many centuries, each of which contributed to the language through their own names. In this work, 200 toponyms from three regions of Great Britain were investigated. According to the origin, the researched toponyms are divided into native and borrowed. Native proper names predominate in England, while toponyms of Scandinavian origin are found in the northern regions and the west of the country. Wales and Scotland are characterized mainly by Celtic names. Borrowed toponyms are distinguished according to four linguistic sources: Celtic, Latin, Scandinavian and Norman-French. English contains more loanwords because it is open to receiving words from other languages due to contact with other cultures and colonial heritage. In general, people who named geographical objects were guided by the features of the landscape where this object was located. This category of toponyms occurs in all three parts of Britain and has many subgroups. The emergence of this group is a logical consequence of the fact that the ancestors of the British named their surroundings according to what they saw. When creating and choosing toponyms, a certain pragmatic orientation can be observed, which depends on various factors, such as the historical context of naming, the level of cultural development, social, political, religious or patriotic motives of persons who give certain names to geographical objects. This layer of vocabulary is of great interest to researchers because it can collect linguistic, sociocultural and historical experience.

The E3 ubiquitin ligase TRIP12 is required for pancreatic acinar cell plasticity and pancreatic carcinogenesis.

The E3 ubiquitin ligase thyroid hormone receptor interacting protein 12 (TRIP12) has been implicated in pancreatic adenocarcinoma (PDAC) through its role in mediating the degradation of pancreas transcription factor 1a (PTF1a). PTF1a is a transcription factor essential for the acinar differentiation state that is notably diminished during the early steps of pancreatic carcinogenesis. Despite these findings, the direct involvement of TRIP12 in the onset of pancreatic cancer has yet to be established. In this study, we demonstrated that TRIP12 protein was significantly upregulated in human pancreatic preneoplastic lesions. Furthermore, we observed that TRIP12 overexpression varied within PDAC samples and PDAC-derived cell lines. We further demonstrated that TRIP12 was required for PDAC-derived cell growth and for the expression of E2F-targeted genes. Acinar-to-ductal cell metaplasia (ADM) is a reversible process that reflects the high plasticity of acinar cells. ADM becomes irreversible in the presence of oncogenic Kras mutations and leads to the formation of preneoplastic lesions. Using two genetically modified mouse models, we showed that a loss of TRIP12 prevented acini from developing ADM in response to pancreatic injury. With two additional mouse models, we further discovered that a depletion of TRIP12 prevented the formation of KrasG12D-induced preneoplastic lesions and impaired metastasis formation in the presence of mutated KrasG12D and Trp53R172H genes. In summary our study identified an overexpression of TRIP12 from the early stages of pancreatic carcinogenesis and proposed this E3 ubiquitin ligase as a novel regulator of acinar plasticity with an important dual role in initiation and metastatic steps of PDAC. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Novel chemokine biomarkers in melanoma†.

The melanoma tumor microenvironment is a complex milieu of cancer, inflammatory, and stromal cells. In this context, chemokines play a pivotal role in recruiting inflammatory cells and influence the tumor, exerting both pro-tumorigenic and anti-tumoral roles. Interactions between these cells is what ultimately hold together and transform the tumor into an efficient machine. A recent study found that chemokines CCL8, CCL15, and CCL20 were upregulated in melanoma cells when co-cultured with macrophages and were associated with poor survival rates. CCL8 and CCL15 also stimulated melanoma cell growth, invasion, and metastasis, and were highly expressed in tumors prone to metastasize, suggesting these chemokines are attractive and independent biomarkers. Understanding the intricated interactions within the tumor microenvironment could lead to prognostic biomarkers and to the development of new therapeutic strategies for melanoma. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Measuring the energy poverty premium in Great Britain and identifying its main drivers based on longitudinal household survey data

Following the consistent hike in energy prices in recent years, energy affordability by low-income households in Great Britain has become a significant concern. These concerns are further compounded by the disproportionate cost of energy that poor households are likely to pay, compared to the non-poor. In this study, we examine the exposure of poor households to energy premiums by measuring the additional costs incurred and identifying the main drivers. We merge household-level data from Understanding Society with energy consumption data from the National Energy Efficiency Data — Framework (NEED). Using the merged dataset and the Theory of Complaints, we propose a new approach to measuring the poverty premium based on the cost per unit of energy incurred by households. Based on a two-stage regression model, our results show that poorer households are likely to pay premiums for energy consumption. Furthermore, among households who incur these energy premiums, poor households pay higher premiums than non-poor households, incurring a cost of between 10%–20% more per unit for both gas and electricity premiums between 2011 and 2019. These relationships are still significant even after addressing the potential endogeneity of poverty, thereby confirming the relationship between energy premiums and poverty. The results also suggest that the other key drivers of electricity and gas premiums are payment methods used, and household characteristics such as the number of adults per household, presence of children, unemployed adults and pensioners.

Some issues of Russia's transport policy in the context of Western sanctions

The aspects of Russia's transport policy at the present stage in the context of the tightening of Western sanctions pressure are considered. The project of the North-South international transport corridor is considered as a transport response to attempts to push Russia away from the global South. Particular attention is paid to the political and technological aspects of the formation of the international transport corridor of the North-South project, the negative consequences of the sanctions imposed by Western countries against the transport industry of Russia are shown. An assessment of the actions of the United States and partners to counteract the creation of the North-South international transport corridor through the formation of alternative transport projects of the Lapis Lazuli Corridor and the Zangezur land transport corridor is given. Showing actions of the Government of the Russian Federation to defend the North-South project. In order to counter the threats from Britain and Great Britain, Russia and its partners in the formation of the North-South International Transport Corridor need to preserve sovereignty in international relations, counteract the interference of third countries in their plans, and strengthen the collective military security of their countries. It is important not to succumb to provocations, to show flexibility and mutual willingness to cooperate. This will not only help to overcome obstacles to the implementation of the North-South ITC project, but will also help the participating countries to move forward on integration issues, strengthening their relations.

Analyses of academician cohorts generate biased pandemic excess death estimates

ObjectiveDeath data from cohorts of academicians have been used to estimate pandemic excess deaths. We aimed to evaluate the validity of this approach. Study Design and SettingData were analyzed from living and deceased member lists from Mainland China, UK and Greece academies; and Nobel laureates (and US subset thereof). Samples of early elected academicians were probed for unrecorded deaths; datasets overtly missing deaths were excluded from further analyses. Actuarial risks were compared against the general population in the same country in respective age strata. Relative incidence risk increases in death in active pandemic periods were compared to population-wide pandemic excess death estimates for the same country. ResultsRoyal Society and Academy of Athens datasets overtly missed deaths. Prepandemic death rates were 4- to 12-fold lower in the Chinese Academy of Engineering (CAE) vs respective age strata of the Mainland China population. A +158% relative increase in death risk was seen in CAE data during the first 12-month of wide viral spread. Both increases (+34% in British Academy) and decreases (−27% in US Nobel laureates) in death rates occurred in pandemic (2020-22) vs prepandemic (2017-19) years; point estimates were far from known excess deaths in the respective countries (+6% and +14%, respectively). Published excess death estimates for urban-dwelling Mainland China selectively analyzed CAE that had double the pandemic death rates than another Chinese academy (Chinese Academy of Sciences). ConclusionMissingness, lack of representativeness, large uncertainty, and selective analysis reporting make data from academy rosters unreliable for estimating general population excess deaths.

11United Kingdom Supreme Court, Independent Workers Union of Great Britain v. Central Arbitration Committee, 21 November 2023

11United Kingdom Supreme Court, Independent Workers Union of Great Britain v. Central Arbitration Committee, 21 November 2023

Should cows graze? A relational approach to understanding farmer perspectives on the ethics of grazing and indoor dairy systems

AbstractIn the United Kingdom, around 20% of dairy farms house cows all year round. Research suggests that farmers value animal health and comfort over the expression of natural behaviour through grazing. The concept of natural behaviour is notoriously complex, however. The article reframes the topic of grazing through a relational approach to understand farmer views on the practice in Great Britain, using qualitative interviews. The article also considers critiques of the relational approach. In this study, participants were reluctant to see a distinction between farms that graze and those that do not in terms of animal welfare, but they also valued the positive affective experience of grazing their cows on their own farm. The article argues that the latter account is not adequately included in debates about grazing. What this account excludes is the situated nature and limitations of relationships on farm even when cows graze.

Reanalysing Ireland’s Exit from the Commonwealth 1948–49: The Brexit Isles’ Alter Ego?

ABSTRACT This article reexplores Ireland’s final exit from the Commonwealth in 1948–49, deploying Brexit as a comparative heuristic and organising device. The existing literature has stressed both Ireland’s symbolic motives in fully breaking with the Crown and how it retained many the advantages of Commonwealth membership whilst avoiding its obligations. It is true that, at least from the later 1930s, Ireland was more akin to an associate as opposed to a full Commonwealth member and that both significant support for the Irish position from Commonwealth members with large Irish diaspora populations and decentralisation in the Commonwealth itself made for a relatively hospitable negotiating environment. Nevertheless, the Brexit comparison helps highlights the considerable trade and citizenship links, including with the UK, which were linked to Commonwealth association and which secession thereby put at risk. It similarly highlights the price Ireland paid for its exit including a public commitment to make reciprocal citizenship rights generally available to all Commonwealth members, a strengthening of Northern Ireland’s links with Great Britain and a loss of participation rights in key Commonwealth preference, Sterling Area and related fora. The ultimately rather limited significance of that price may relate more to a subsequent fundamental refocusing of both Irish and UK geographic priorities towards Europe in subsequent decades.

Non-market value losses to coastal ecosystem services and wetlands from sea-level rise and storm surge, 2050 to 2100: The Kimberley Region, Western Australia

Accelerating climate change from the thermal expansion of oceans and losses from terrestrial glaciers and ice sheets causes sea level rise (SLR), damaging coastal ecosystems and generating non-market value losses. Using an innovative Artificial Intelligence (AI) projection method and 18 existing geographical SLR projections, we project future sea level rise and storm surge (SLR/S) for the 1600 km coastline of the Kimberley Region, Western Australia, a region with a larger surface area than Great Britain, Ireland, and Portugal combined and with a permanent population of 40,000 people of which more than 16,000 identify as Indigenous. Using our projected coastal area inundation from future SLR, we estimated the non-market value losses of the Kimberley's coastal ecosystem and wetlands with projected SLR/S to 2050 and 2100 for Representative Concentration Pathway (RCPs) 4.5 and 8.5. Average annual non-market losses from SLR/S in 2050 and 2100 in the Kimberley are large relative to the size of the regional economy and are estimated to range from A$2.7 to A$4.3 billion (2050) and A$8.1 to A$15.8 billion (2100), depending on the RCP and temperature pathway. Our findings highlight the need for adequately resourced community-based approaches to climate adaptation.

Epistemic Domination and ‘Gender Identity Fraud’ Prosecutions

ABSTRACT By analyzing the so-called ‘gender identity fraud’ cases of recent years in Great Britain, I will show that these cases fall outside Miranda Fricker’s theoretical framework of epistemic injustice. In building on Talia Bettcher’s work on the deceiver and pretender stereotypes of trans people, I will provide an analysis of the convictions and argue that these cases are examples of epistemic domination. First, I will argue that testimonial injustice as a concept is inapt to explain why the consent given in these cases was considered vitiated in the trials. Second, I will show how hermeneutical injustice falls short in elucidating the power structures at play and obscures our understanding of the possibilities and responsibilities of the respective epistemic agents. Moreover, I argue that these cases are morally and politically wrong because these convictions create a legal double-bind for trans people. At the end of my discussion, I develop the concept of relational epistemic domination, which is suffered by partners of trans people and which might affect the complainants in these cases. I will conclude that states must refrain from prosecuting gender identity fraud, and to theorize similar cases adequately, we must do so as cases of epistemic domination.

Widespread flooding dynamics under climate change: characterising floods using grid-based hydrological modelling and regional climate projections

Abstract. An event-based approach has been used to explore the potential effects of climate change on the spatial and temporal coherence of widespread flood events in Great Britain. Time series of daily mean river flow were generated using a gridded national-scale hydrological model (Grid-to-Grid) driven by a 12-member ensemble of regional climate projections from UK Climate Projections 2018 (UKCP18), for 30-year baseline (1980–2010) and future (2050–2080) time slices. From these, sets of widespread extreme events were extracted. The question of what defines a “widespread flood event” is discussed; here it was defined as an event exceeding an at-site 99.5th percentile (equivalent to 2 d per year) simultaneously over an area of at least 20 km2, with a maximum duration of 14 d. This resulted in a set of 14 400 widespread events: approximately 20 events per year, per ensemble member, per time slice. Overall, results have shown that events are more temporally concentrated in winter in the future time slice compared to the baseline. Distributions of event area were similar in both time slices, but the distribution of at-site return periods showed some heavier tails in the future time slice. Such information could be useful for adaptation planning and risk management for floods under climate change, but the potential future changes have to be interpreted in the context of some differences in event characteristics between the baseline climate-projection-driven model runs and an observation-driven model run. While the focus here is Great Britain, the methods and analyses described could be applied to other regions with hydrological models and climate projections of appropriate resolution.

Памятники армянской архитектуры и топонимики Великобритании / The Monuments of Armenian Architectures and Toponymy in the Great Britain

The article presents the head of a multi-volume atlas of the catalog «The monuments of Armenian architecture and place names abroad». The article briefly presents the existing monuments. The main part of the article is a table-list of Armenian monuments of architecture and toponymy in the Great Britain, after which a list of literature is given

Brexit and Its Consequences for the European Union and Member States, With Particular Emphasis on the Visegrad Group Countries: A Neorealist Analysis

This article focuses on analysing the consequences of Brexit for the European Union and its Member States, with particular emphasis on the Visegrad Group (V4) countries. Through the prism of neorealism theory, the changes in the balance of power and international dynamics resulting from Great Britain’s exit from the EU are analysed. The aim is not only to identify specific Brexit outcomes but also to understand the mechanisms influencing relations among European states, especially in the future. In this context, neorealist analysis becomes a particularly valuable tool, allowing us to view Brexit not only as a one-time incident but also as a manifestation of broader trends in global international relations which may adopt disintegrative stances in the future.

Lessons That Poland Can Learn From Brexit

The UK’s exit from the European Union has had seriously negative consequences for the British economy and society. These consequences can be taken as a serious warning to other EU countries that may wish to follow Britain’s chosen path. The warning is particularly important as regards Poland, where the far right has long been openly calling for a so-called “Polexit”. The aim of this article is to analyse and assess both the current and expected effects of Brexit, as well as the conclusions that Poland can draw from them. After presenting the background of Brexit, this analysis focuses primarily on the effects that Great Britain has experienced in the areas of trade with the EU, along with Brexit’s effects on investment, inflation, immigration, and deregulation. Public opinion survey results are also shown, indicating a negative assessment of Brexit by the majority of British society, which is increasingly demanding the restoration of the country’s ties with the EU. Next, the threats to Poland’s further participation in the EU that have arisen since 2015 are shown. Based on Britain’s experience, it can be predicted that a possible Polexit may hit the Polish economy particularly hard, primarily due to the loss of free access to the EU’s single market and a possible collapse with regard to Polish exports, as well as the predicted massive outflow of capital abroad and decline in the inflow of foreign investments. A Polexit would also mean a loss of EU funding. All this would drastically limit Poland’s development possibilities and would trigger a civilisational degradation of the country.

Конституционно-правовые аспекты языковой политики Великобритании в области поддержки языковых меньшинств

The object of the study is the political and legal aspects of regulating the rights of linguistic minorities in the UK on the example of measures to preserve the Welsh language as part of the national identity of the Welsh. The author characterizes the language policy of Great Britain of this period as a policy of linguistic nationalism of the English language and discrimination against the national languages of other peoples. The article also examines the main regulatory legal acts aimed at expanding the use of the Welsh language and consolidating the status of the Welsh language as the national language of Wales. The main conclusions of this article were the demonstrated specific discriminatory measures used by Britain in relation to the Welsh language, including a ban on the use of the Welsh language as the language of legislation, the language of legal proceedings and restrictions on teaching in Welsh. The study identifies the causes and constitutional and legal factors of the transition from the policy of language discrimination to the policy of dialogue of cultures and the influence of public figures advocating for the preservation and expansion of the use of the Welsh language on the language policy of Great Britain. The constitutional significance of the Provision on the Welsh Language of 2011 is stated, the content of this act is analyzed for the first time in the Russian-language doctrine.

Nicotine strength of e-liquids used by adult vapers in Great Britain: A population survey 2016 to 2024.

In March 2024, the UK government announced plans to introduce a Vaping Products Duty that will tax e-liquids based on their nicotine strength. This study examined trends in the nicotine strength of e-liquids used by adult vapers and differences in those currently used across relevant subgroups. Nationally-representative, cross-sectional household survey, July 2016 to January 2024. Great Britain. 7981 adult vapers. Participants were asked whether the e-cigarette they mainly use contains nicotine (yes/no) and the e-liquid strength (no nicotine, >0-≤ 6, 7-11, 12-19 or ≥20 mg/ml). We also collected information on the main device type used (disposable/refillable/pod), age, gender, occupational social grade, history of ≥1 mental health conditions, smoking status and (among past-year smokers) level of cigarette addiction. The proportion of vapers in England using high-strength (≥20 mg/ml) e-liquids increased from an average of 3.8% (95% confidence interval [CI] = 2.9-5.0) up to June 2021 to 32.5% (CI = 27.9-37.4) in January 2024 (the vast majority of whom [93.3% in January 2024] reported using exactly 20 mg/ml; the legal limit). This rise was most pronounced among those using disposable e-cigarettes, those aged 18-24 years and all smoking statuses (including never smokers) except long-term (≥1y) ex-smokers. Of those surveyed in 2022-2024 in Great Britain, overall, 89.5% (CI = 88.1-90.8) said they usually used e-cigarettes containing nicotine, 8.7% (CI = 7.5-10.0) used nicotine-free e-cigarettes, and 1.8% (CI = 1.2-2.4) were unsure. The proportion using ≥20 mg/ml was higher among those mainly using disposable (47.9%) compared with pod (16.3%) or refillable (11.5%) devices; never smokers (36.0%), current smokers (28.8%) or recent (<1y) ex-smokers (27.4%), compared with long-term ex-smokers (13.9%); and younger (16-24y; 44.2%) compared with older (≥25y; range 9.4-25.1%) age groups. There were no notable differences across other subgroups of interest. Use of high-strength nicotine e-liquids in England appears to have increased sharply in recent years. Most adult vapers in Great Britain appear to use e-cigarettes that contain nicotine but different subgroups use different strengths: nicotine strengths tend to be higher among those who mainly use disposable devices and those aged 16-24y, and lower among long-term ex-smokers.

Российско-британские отношения XVIII века в трудах Дэвида Бейна Хорна (часть 4)

This publication serves as the concluding article in a series of works by the author examining Russo-British relations in the XVIII century within the scientific heritage of British historian David Bain Horn. The object of study in this article is the relations between Russia and Great Britain as presented in Horn’s monograph “Great Britain and Europe in the XVIII Century”. The article explores how Russo-British relations of the XVIII century are portrayed in Horn’s research and the assessments he provides regarding these relations. Through a comparative analysis, the author of the article not only traces the evolution of D.B. Horn’s views on the relations between Britain and Russia in the XVIII century but also identifies differences from the perspectives and assessments of Soviet and Russian historians.