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Waves of psychological research over 50 years have resulted in the development of scales to measure psychological resilience. Multiple psychological resilience definitions and factors have emerged during this time, making its measurement complex. The overall aim of the review was to identify and describe developments in the measurement of psychological resilience in the clinical mental healthcare setting. Specific objectives included (1) consideration of the validity and reliability of psychological resilience scales, (2) the effectiveness of the scales in clinical mental healthcare settings and (3) to identify the scope that resilience factors are addressed in the included scales. It provides a timely update regarding psychological resilience measurement tools and considers further developments that may be required. Between 2011 and 2024, databases were searched, and English‐language, peer‐reviewed papers with full text were extracted. Eligible studies were those reporting validated existing resilience measures or the outcomes of new measures for use in clinical mental healthcare settings. Seventeen studies met the inclusion criteria. The review demonstrated that psychological resilience measures require further development, particularly focusing on the utility of measurement tools in clinical mental healthcare settings. In this review, we highlight an existing gap in resilience measurement and underscore the need for a new measure of psychological resilience that can effectively assess individuals' subjective experience of their psychological resilience in clinical mental healthcare settings. The currently available psychological resilience measures included in this review do not directly reflect all the factors that might impact a client's depression or anxiety and warrant further research. [ABSTRACT FROM AUTHOR]

Purpose: Older adults admitted to the intensive care unit (ICU) usually have fair baseline functional capacity, yet their age and frailty may compromise their management. We compared the characteristics and management of older (≥ 75 years) versus younger adults hospitalized in ICU with hospital-acquired bloodstream infection (HA-BSI). Methods: Nested cohort study within the EUROBACT-2 database, a multinational prospective cohort study including adults (≥ 18 years) hospitalized in the ICU during 2019–2021. We compared older versus younger adults in terms of infection characteristics (clinical signs and symptoms, source, and microbiological data), management (imaging, source control, antimicrobial therapy), and outcomes (28-day mortality and hospital discharge). Results: Among 2111 individuals hospitalized in 219 ICUs with HA-BSI, 563 (27%) were ≥ 75 years old. Compared to younger patients, these individuals had higher comorbidity score and lower functional capacity; presented more often with a pulmonary, urinary, or unknown HA-BSI source; and had lower heart rate, blood pressure and temperature at presentation. Pathogens and resistance rates were similar in both groups. Differences in management included mainly lower rates of effective source control achievement among aged individuals. Older adults also had significantly higher day-28 mortality (50% versus 34%, p < 0.001), and lower rates of discharge from hospital (12% versus 20%, p < 0.001) by this time. Conclusions: Older adults with HA-BSI hospitalized in ICU have different baseline characteristics and source of infection compared to younger patients. Management of older adults differs mainly by lower probability to achieve source control. This should be targeted to improve outcomes among older ICU patients. [ABSTRACT FROM AUTHOR]

This article provides an introduction to 'chemsex' and chemsex related support services. Chemsex definitions and prevalence are described, alongside the response from services so far. Theoretical understandings and empirical findings so far are discussed alongside presenting some of the main issues currently for services. The involvement of Clinical Psychologists (both in specialist and non-specialist settings) is considered. Finally, a practice example of one of the services developed in London is outlined, and recommendations for clinicians provided. [ABSTRACT FROM AUTHOR]

Purpose of Review: This comprehensive review discusses the complex relationship between Alzheimer's disease (AD) and osteoporosis, two conditions that are prevalent in the aging population and result in adverse complications on quality of life. The purpose of this review is to succinctly elucidate the many commonalities between the two conditions, including shared pathways, inflammatory and oxidative mechanisms, and hormonal deficiencies. Recent Findings: AD and osteoporosis share many aspects of their respective disease-defining pathophysiology. These commonalities include amyloid beta deposition, the Wnt/β-catenin signaling pathway, and estrogen deficiency. The shared mechanisms and risk factors associated with AD and osteoporosis result in a large percentage of patients that develop both diseases. Previous literature has established that the progression of AD increases the risk of sustaining a fracture. Recent findings demonstrate that the reverse may also be true, suggesting that a fracture early in the life course can predispose one to developing AD due to the activation of these shared mechanisms. The discovery of these commonalities further guides the development of novel therapeutics in which both conditions are targeted. Summary: This detailed review delves into the commonalities between AD and osteoporosis to uncover the shared players that bring these two seemingly unrelated conditions together. The discussion throughout this review ultimately posits that the occurrence of fractures and the mechanism behind fracture healing can predispose one to developing AD later on in life, similar to how AD patients are at an increased risk of developing fractures. By focusing on the shared mechanisms between AD and osteoporosis, one can better understand the conditions individually and as a unit, thus informing therapeutic approaches and further research. This review article is part of a series of multiple manuscripts designed to determine the utility of using artificial intelligence for writing scientific reviews. [ABSTRACT FROM AUTHOR]

The new government faces an urgent challenge: revitalising the UK's crumbling public services without major increases in public spending. While technological change holds promise, UK digital government initiatives have failed to reach their full potential over the past twenty‐five years. This article argues that the latest generation of 'data‐intensive' technologies, including data science and AI, can succeed where past efforts have faltered. We provide a roadmap for how to harness the power of recent technologies for a more productive and equitable public sector, and pinpoint the organisational changes necessary to develop progressive, technologically enhanced public services. [ABSTRACT FROM AUTHOR]

In Hood's (1983) classic "NATO" scheme, nodality—centrality and visibility in information networks—is one of the four tools of government. Despite its potential as a resource to effect policy change, contemporary scholars have largely neglected this unique policy tool. However, the growing prominence of digital platforms in public life prompts a rediscovery of this concept. The decisive shift is the parallel growth of citizen nodality, which can increase societal capacity and enhance government nodality, partly by allowing citizens to challenge government nodality. Moreover, citizen nodality and government nodality can interact to promote more democratic government. With the aim of rediscovering and updating nodality, this article defines the concept, reviews how the modern digital landscape has transformed the practice of nodality, and proposes a conceptual and methodological toolkit. The goal is to understand how nodality may be more effectively used by policy‐makers while at the same time fostering democratic governance. [ABSTRACT FROM AUTHOR]

Recent advancements in large language models (LLMs) have raised the prospect of scalable, automated, and fine-grained political microtargeting on a scale previously unseen; however, the persuasive influence of microtargeting with LLMs remains unclear. Here, we build a custom web application capable of integrating self-reported demographic and political data into GPT-4 prompts in real-time, facilitating the live creation of unique messages tailored to persuade individual users on four political issues. We then deploy this application in a preregistered randomized control experiment (n = 8,587) to investigate the extent to which access to individual-level data increases the persuasive influence of GPT-4. Our approach yields two key findings. First, messages generated by GPT-4 were broadly persuasive, in some cases increasing support for an issue stance by up to 12 percentage points. Second, in aggregate, the persuasive impact of microtargeted messages was not statistically different from that of non-microtargeted messages (4.83 vs. 6.20 percentage points, respectively, P = 0.226). These trends hold even when manipulating the type and number of attributes used to tailor the message. These findings suggest--contrary to widespread speculation--that the influence of current LLMs may reside not in their ability to tailor messages to individuals but rather in the persuasiveness of their generic, nontargeted messages. We release our experimental dataset, GPTarget2024, as an empirical baseline for future research. [ABSTRACT FROM AUTHOR]

This paper presents data derived from a larger study related to the expectations and experiences of international students from the People's Republic of China with regard to studying in Australian secondary schools. The study involved 116 international students, and data were collected in two phases using questionnaires and semi-structured interviews. Findings suggest that English language experiences are a key concern and students do not always develop English language skills as expected during their period of study in Australia. To reduce dissonance between expectations and experiences of English language learning in Australia, it is recommended that substantial, ongoing English language support is embedded within the core curriculum for international students in Australian secondary schools. [ABSTRACT FROM AUTHOR]

University governing bodies, especially academic boards, play a crucial role in policy formation. However, due to the predominance of managerial values over academic values in the policy-making process, a persistent divide exists between policy formulation and implementation. This divide results from the marginalisation of academics and the dominance of managerial authority figures within these bodies. Our study investigates the latter to determine the precise Foucauldian apparatus used by authority figures to influence policy-making meetings. Using an innovative arts-based method, we analyse ethnographic vignettes through a Foucauldian lens and transform them into collages depicting the apparatus used by authority figures: Strategic Managerial Monumentalism, Managerial Historical Revisionism, Managerial Discursive Dominance, Managerial Panoptic Surveillance, and Managerial Normalisation. We contend that only a well-defined separation of governance powers can effectively counter the encroachment of managerialism and uphold the democratic representation of academic values in university policies to bridge the policy-practice divide. [ABSTRACT FROM AUTHOR]

The function and phenotype of γδ T cells in the context of common variable immunodeficiency (CVID) has not been explored. CVID is a primary immunodeficiency disorder characterized by impaired antibody responses resulting in increased susceptibility to infections. γδ T cells are a subset of unconventional T cells that play crucial roles in host defence against infections. In this study, we aim to determine the roles and functions of γδ T cells in CVID. We observe a higher frequency of Vδ1 + γδ T cells compared to healthy controls, particularly in older patients. We also find a higher proportion of effectormemory Vδ1 + γδ T cells and a more clonal T cell receptor (TCR) repertoire in CVID. The most significant driver of the Vδ1 + γδ T cell expansion and phenotype in CVID patients is persistent cytomegalovirus (CMV) viremia. These findings provide valuable insights into γδ T cell biology and their contribution to immune defence in CVID. [ABSTRACT FROM AUTHOR]

As aquatic invasive species spread, their impacts on native systems are variable and important to understand from a management perspective. DNA sequencing and morphological analysis of stomach contents can provide insight into the diet of invasive opportunistic feeders, such as smallmouth bass (Micropterus dolomieu). Since their illegal introduction in 2017, smallmouth bass have proliferated in Cultus Lake, British Columbia and potential impacts on two species-at-risk (sockeye salmon and pygmy sculpin) are currently unknown. Bass (n = 204) were sampled in the spring/summer of 2020–2021 in Cultus Lake. DNA barcoding (n = 145) and visual analysis (n = 204) of diet were completed. Diet composition, factors influencing the predation of species-at-risk, and dietary shifts were analyzed. DNA analysis identified 32 more taxa at the family level than morphological analysis. Multiple logistic regression showed that bass were more likely to predate on Oncorhynchus nerka within the bass spawning grounds, and over 90% of bass had sculpin in their diets. Diet composition did not shift as bass size changed, demonstrating sustained predation on fish from 100 to > 300 mm total length. These results highlight the importance of understanding the potential impacts of an invasive species before investing in suppression to create effective plans and leverage funding opportunities. [ABSTRACT FROM AUTHOR]

University institutional policy is poorly understood. While policy is required by law for universities to accept funding and is revered for articulating values, mitigating risk, and guiding practice, policy is frequently considered absurd and resisted in practice. This is the policy-practice divide. To gain a better understanding of this divide and the nature of the resistance, we asked policy actors to describe their experiences with policy development, implementation, enactment, and review. We asked: If policy is absurd, what is the nature of the relationship between policy and university management, and how do those who enact policy deal with this absurdity? We discovered that university management has an infinitely regressive self-fulfilling relationship with policy because they intentionally exclude the workforce from policy-making and see themselves as solely responsible for policy interpretation and implementation. However, when Kierkegaard's concepts of absurdity, faith, hope, and doubt are applied to policy actors' experiences, we see that resistance can be characterised positively as a 'leap of faith', where those who enact policy overcome their doubts and reinterpret it to achieve some semblance of good. This is an unintended consequence for managerialism, as deliberately creating a policy-practice divide solicits resistive 'good' practices from policy actors. [ABSTRACT FROM AUTHOR]

Purpose of Review: This Comment represents three review articles on the relationship between Alzheimer's disease, osteoporosis, and fracture in an exploration of the benefits that AI can provide in scientific writing. The first drafts of the articles were written (1) entirely by humans; (2) entirely by ChatGPT 4.0 (AI-only or AIO); and (3) by humans and ChatGPT 4.0 whereby humans selected literature references, but ChatGPT 4.0 completed the writing (AI-assisted or AIA). Importantly, each review article was edited and carefully checked for accuracy by all co-authors resulting in a final manuscript which was significantly different from the original draft. Recent Findings: The human-written article took the most time from start to finish, the AI-only article took the least time, and the AI-assisted article fell between the two. When comparing first drafts to final drafts, the AI-only and AI-assisted articles had higher percentages of different text than the human article. The AI-only paper had a higher percentage of incorrect references in the first draft than the AI-assisted paper. The first draft of the AI-assisted article had a higher similarity score than the other two articles when examined by plagiarism identification software. Summary: This writing experiment used time tracking, human editing, and comparison software to examine the benefits and risks of using AI to assist in scientific writing. It showed that while AI may reduce total writing time, hallucinations and plagiarism were prevalent issues with this method and human editing was still necessary to ensure accuracy. [ABSTRACT FROM AUTHOR]

Purpose of Review: This comprehensive review delves into the intricate interplay between Alzheimer's disease (AD) and osteoporosis, two prevalent conditions with significant implications for individuals' quality of life. The purpose is to explore their bidirectional association, underpinned by common pathological processes such as aging, genetic factors, inflammation, and estrogen deficiency. Recent Findings: Recent advances have shown promise in treating both Alzheimer's disease (AD) and osteoporosis by targeting disease-specific proteins and bone metabolism regulators. Monoclonal antibodies against beta-amyloid and tau for AD, as well as RANKL and sclerostin for osteoporosis, have displayed therapeutic potential. Additionally, ongoing research has identified neuroinflammatory genes shared between AD and osteoporosis, offering insight into the interconnected inflammatory mechanisms. This knowledge opens avenues for innovative dual-purpose therapies that could address both conditions, potentially revolutionizing treatment approaches for AD and osteoporosis simultaneously. Summary: This review underscores the potential for groundbreaking advancements in early diagnosis and treatment by unraveling the intricate connection between AD and bone health. It advocates for a holistic, patient-centered approach to medical care that considers both cognitive and bone health, ultimately aiming to enhance the overall well-being of individuals affected by these conditions. This review article is part of a series of multiple manuscripts designed to determine the utility of using artificial intelligence for writing scientific reviews. [ABSTRACT FROM AUTHOR]

Purpose of Review: This review examines the linked pathophysiology of Alzheimer's disease/related dementia (AD/ADRD) and bone disorders like osteoporosis. The emphasis is on "inflammaging"—a low-level inflammation common to both, and its implications in an aging population. Recent Findings: Aging intensifies both ADRD and bone deterioration. Notably, ADRD patients have a heightened fracture risk, impacting morbidity and mortality, though it is uncertain if fractures worsen ADRD. Therapeutically, agents targeting inflammation pathways, especially Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) and TNF-α, appear beneficial for both conditions. Additionally, treatments like Sirtuin 1 (SIRT-1), known for anti-inflammatory and neuroprotective properties, are gaining attention. Summary: The interconnectedness of AD/ADRD and bone health necessitates a unified treatment approach. By addressing shared mechanisms, we can potentially transform therapeutic strategies, enriching our understanding and refining care in our aging society. This review article is part of a series of multiple manuscripts designed to determine the utility of using artificial intelligence for writing scientific reviews. [ABSTRACT FROM AUTHOR]

Red sensitivity is the exception rather than the norm in most animal groups. Among species with red sensitivity, there is substantial variation in the peak wavelength sensitivity (λmax) of the long wavelength sensitive (LWS) photoreceptor. It is unclear whether this variation can be explained by visual tuning to the light environment or to visual tasks such as signalling or foraging. Here, we examine long wavelength sensitivity across a broad range of taxa showing diversity in LWS photoreceptor λmax: insects, crustaceans, arachnids, amphibians, reptiles, fish, sharks and rays. We collated a list of 161 species with physiological evidence for a photoreceptor sensitive to red wavelengths (i.e. λmax ≥ 550 nm) and for each species documented abiotic and biotic factors that may be associated with peak sensitivity of the LWS photoreceptor. We found evidence supporting visual tuning to the light environment: terrestrial species had longer λmax than aquatic species, and of these, species from turbid shallow waters had longer λmax than those from clear or deep waters. Of the terrestrial species, diurnal species had longer λmax than nocturnal species, but we did not detect any differences across terrestrial habitats (closed, intermediate or open). We found no association with proxies for visual tasks such as having red morphological features or utilising flowers or coral reefs. These results support the emerging consensus that, in general, visual systems are broadly adapted to the lighting environment and diverse visual tasks. Links between visual systems and specific visual tasks are commonly reported, but these likely vary among species and do not lead to general patterns across species. [ABSTRACT FROM AUTHOR]

A series of non‐enzymatic electrochemical glucose sensors were prepared by template‐assisted electrodeposition of nickel to produce nickel nanowire arrays (NiNWAs) of varying lengths. These electrodes were analyzed for their performance as non‐enzymatic glucose sensors, in order to explore the relationship between nanowire structure and electrochemical sensor performance. All of the NiNWAs, regardless of length, had linear responses to glucose in the 0.05–10 mM range. However, an inverse relationship between wire length and sensitivity was observed: the shortest of the NiNWAs had a sensitivity of 160 μA mM−1 cm−2, while the longest NiNWA had a sensitivity of only 100 μA mM−1 cm−2. This indicates that, with no other change to material parameters, choosing an optimum length of nanowire provides significant improvement in performance. No change in electrochemical mechanism was observed by cyclic voltammetry, and no significant loss of selectivity was observed with varying nanowire length. This study demonstrates that the structural optimization of an electrode can provide significant performance enhancement for nickel‐based electrochemical sensors. [ABSTRACT FROM AUTHOR]

Pacific Island communities are facing disruptions to supply chains from natural disasters and a changing global environment, which have become more acute following the COVID-19 pandemic. Further, it has been demonstrated how flexible systems can enhance resilience in low-resource environments, such as adapting to changing consumer needs and minimizing supply chain disruptions. This paper considers how the development of a flexible system for conducting a risk assessment on a product that was developed and manufactured in a Makerspace environment would have application in Pacific Island communities to improve resilience. Using a participative action research (PAR) approach, a traditional product risk assessment is refined through iterative PAR cycles to reconceptualize it into a structured simplified risk process. The resulting product development risk assessment process (PDRAP) demonstrates that it is possible to adapt a detailed systematic risk assessment process, such as hazard and operability analysis (HAZOP), to be more suitable and effective for low-resource situations requiring flexible solutions. The improved process provides greater system flexibility to empower people to develop products which may improve their resilience in an ever changing and complex world. The PDRAP process can improve product design and adaptability which assists safeguarding supply chains from system wide disruptions. With the emergence of Makerspaces in developing countries for supply chain recovery from natural disasters and a changing national strategy, the PDRAP provides communities with a low-resource approach for risk assessment to ensure the safe use of products fabricated using emerging low-volume, rapid prototyping, and manufacturing technology. [ABSTRACT FROM AUTHOR]

Copyright of Medieval Archaeology is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

A correction is presented to the article the correction of an author's name in a previously published study on the presentation, management, and outcomes of older versus younger adults with hospital-acquired bloodstream infections in the intensive care unit.

During excavations undertaken for the Dover Western Dock Revival Scheme, Kent, UK, Archaeology South-East (ASE; UCL Institute of Archaeology) encountered substantial remains associated with the development of the port of Dover. Despite natural limitations, especially in the form of silting from the River Dour and longshore drift, Dover has historically been a strategic location in which to maintain a port. The remains presented here comprise a nationally significant waterfront revealed during the revival scheme; that is, the Tudor engineering commonly attributed to Sir Thomas Digges, overseen by the Privy Council and commissioned by Elizabeth I. [ABSTRACT FROM AUTHOR]

A 10‐month‐old female, neutered French Bulldog presented with a history of unilateral right‐sided intermittent conjunctivitis and exophthalmos. The patient suffered blunt force trauma to the right eye after a tennis ball impact approximately five months prior to presentation. Examination identified the patient was visual with exophthalmos, lateral strabismus, conjunctival hyperaemia, episcleral congestion, and papilloedema. Magnetic resonance imaging and ultrasonography identified an approximately two centimeter diameter fluid‐filled structure directly posterior to the globe leading to displacement of the optic nerve and distortion of the posterior globe wall. Centesis of the lesion demonstrated neutrophilic and macrophagic inflammation with evidence of prior hemorrhage. Within four weeks, the structure had re‐filled to its original size and was subsequently excised in its entirety, via a lateral orbitotomy. Histopathologic findings indicated a non‐keratinising orbital cyst, the lining of which was consistent with a respiratory epithelial cyst. Recurrence had not occurred seven months' post‐surgery. To the author's knowledge, previous reports of retrobulbar respiratory epithelial cysts have not been documented in animals. [ABSTRACT FROM AUTHOR]

International students in the secondary school sector are a particularly vulnerable group due to their age and status as unaccompanied minors. The establishment of friendships is an important component of the adjustment for these students as they transition into their new school environments. This paper presents issues related to friendships, investigated as part of a larger study examining the motivations, expectations and experiences of international students from the People's Republic of China studying in Australian secondary schools. Data were collected in two phases from 116 international students and 10 teachers using questionnaires and semi-structured interviews, and descriptive analyses employed. Because there is a paucity of information about the experiences of international secondary school students, this was an exploratory study that has contributed understanding of the lived experiences of a small group of international students from mainland China. The study identified that expectations regarding the establishment of friendships are not being met, and that international students from China are seeking more opportunities to form relationships with Australian peers. To reduce dissonance between expectations and experiences of studying in Australia, it is recommended that Australian schools work with both international and domestic students to provide authentic opportunities to build peer relationships. [ABSTRACT FROM AUTHOR]

Ovarian absence is an uncommon condition that most frequently presents unilaterally. Several etiologies for the condition have been proposed, including torsion, vascular accident, and embryological defect. A systematic review was conducted to describe the clinical presentation of ovarian absence, as well as its associations with other congenital anomalies, through a systematic search of Cochrane Library, ClinicalTrials.gov, Google Scholar, Ovid Embase, Ovid Medline, PubMed, Scopus, and Web of Science. Exclusion criteria included cases with suspicion for Differences of Sex Development, lack of surgically-confirmed ovarian absence, and karyotypes other than 46XX. Our search yielded 12,120 citations, of which 79 studies were included. 10 additional studies were found by citation chasing resulting in a total 113 cases including two unpublished cases presented in this review. Abdominal/pelvic pain (30%) and infertility/subfertility (19%) were the most frequent presentations. Ovarian abnormalities were not noted in 28% of cases with pre-operative ovarian imaging results. Approximately 17% of cases had concomitant uterine abnormalities, while 22% had renal abnormalities. Renal abnormalities were more likely in patients with uterine abnormalities (p < 0.005). Torsion or vascular etiology was the most frequently suspected etiology of ovarian absence (52%), followed by indeterminate (27%) and embryologic etiology (21%). Most cases of ovarian absence are likely attributable to torsion or vascular accidents, despite many references to the condition as "agenesis" in the literature. Imaging may fail to correctly diagnose ovarian absence, and diagnostic laparoscopy may be preferable in many cases as genitourinary anatomy and fertility considerations can be assessed during the procedure. Fertility is likely minimally or not affected in women with unilateral ovarian absence. [ABSTRACT FROM AUTHOR]

The Faculty of Social and Historical Sciences at UCL highlighted heritage and conservation, the environment and biodiversity as key challenges to be addressed as part of its Strategic Vision for 2019-29. Staff at Archaeology South-East (ASE) are actively pursuing research into livestock and landscapes and how knowledge of past farming regimes has wider public benefit in terms of informing modern choices regarding food production, sustainability and nature recovery. The author of the present article has also engaged with conservation bodies on aspects of historic grazing and current rewilding projects. This article is intended as an introduction to the essential elements of this work, highlighting how archaeologists and heritage professionals can contribute to debates surrounding the future of our countryside. It draws on a previous blog post as well as themes pursued for associated publication outputs. [ABSTRACT FROM AUTHOR]

Stenosis of the cerebral aqueduct (CA) is featured in many studies relating to elevated intracranial cerebral pressures. It also presents a challenging situation to clinicians. Compressive forces play a lead role in pathological situations such as the presence of tumors and hence can cause obstruction to the flow of cerebrospinal fluid (CSF). Because of this barrier, excessive retention of CSF in the ventricles can occur. This, in turn, can contribute to increased pressure gradients inside the cranium. Most of the numerical models in the literature are restricted to modeling the CSF flow by considering the ventricle walls as rigid material, although in reality they are deformable. This paper, therefore, addresses the same from a holistic perspective by taking into consideration the dynamics of the flexible characteristics of the ventricular wall. It adds novelty to this field by reconstructing anatomically realistic ventricular wall behavior. To do this, the authors aim to develop a computational model of stenosis of the CA due to a brain tumor by invoking a fluid–structure interaction (FSI) method. The proposed three-dimensional FSI model is simulated under two cases: first, simulation of the pre-stenosis case with no interaction of tumor forces and, secondly, a stenosis condition with dynamic interaction of tumor forces. Comparison of the forces with and without a tumor reveals a marked obstruction of CSF outflow after the third ventricle and CA. In addition, a drastic rise in CSF velocity from 21.2 mm/s in the pre-stenosis case to 54.1 mm/s in the stenosis case is observed, along with a net increase in deformation of 0.144 mm on the walls of the ventricle. This paper makes a significant contribution to brain simulation studies for pressure calculations, in which the presence of tumors is a major concern. [ABSTRACT FROM AUTHOR]

This study investigates the linguistic expression of bring and take events and more generally of the semantic domain of directed caused accompanied motion ('directed CAM') across a sample of eight languages of the Pacific and the Americas. Unlike English, the majority of languages in our sample do not lexicalise directed CAM events by simple verbs, but rather encode the defining meaning components – caused motion, accompaniment, and directedness – in morphosyntactically complex constructions. The study shows a high degree of crosslinguistic diversity, even among closely related languages. Meaning components are contributed to directed CAM expressions by a mix of lexical semantics, morphosyntax, and pragmatic means. The study proposes a text-based, semantic typology of directed CAM events by drawing on corpus data from endangered languages. [ABSTRACT FROM AUTHOR]

The human insulin receptor signalling system plays a critical role in glucose homeostasis. Insulin binding brings about extensive conformational change in the receptor extracellular region that in turn effects trans-activation of the intracellular tyrosine kinase domains and downstream signalling. Of particular therapeutic interest is whether insulin receptor signalling can be replicated by molecules other than insulin. Here, we present single-particle cryoEM structures that show how a 33-mer polypeptide unrelated to insulin can cross-link two sites on the receptor surface and direct the receptor into a signalling-active conformation. The 33-mer polypeptide engages the receptor by two helical binding motifs that are each potentially mimicable by small molecules. The resultant conformation of the receptor is distinct from—but related to—those in extant three-dimensional structures of the insulin-complexed receptor. Our findings thus illuminate unexplored pathways for controlling the signalling of the insulin receptor as well as opportunities for development of insulin mimetics. The regulation of plasma glucose levels is effected by insulin. Here, the authors reveal atomic detail of how peptides distinct from insulin bind to and activate the insulin receptor, with implications for design of small-molecule insulin mimetics. [ABSTRACT FROM AUTHOR]

The retrosplenial cortex (RSC) plays a significant role in spatial learning and memory and is functionally disrupted in the early stages of Alzheimer's disease (AD). In order to investigate neurophysiological correlates of spatial learning and memory in this region we employed in vivo electrophysiology in awake and freely moving male mice, comparing neural activity between wild-type and J20 mice, a transgenic model of AD-associated amyloidopathy. To determine the response of the RSC to environmental novelty local field potentials (LFPs) were recorded while mice explored novel and familiar recording arenas. In familiar environments we detected short, phasic bursts of β (20--30 Hz) oscillations (β bursts), which arose at a low but steady rate. Exposure to a novel environment rapidly initiated a dramatic increase in the rate, size and duration of β bursts. Additionally, h-α/β cross-frequency coupling was significantly higher during novelty, and spiking of neurons in the RSC was significantly enhanced during β bursts. Finally, excessive β bursting was seen in J20 mice, including increased b bursting during novelty and familiarity, yet a loss of coupling between β bursts and spiking activity. These findings support the concept that b bursting may be responsible for the activation and reactivation of neuronal ensembles underpinning the formation and maintenance of cortical representations, and that disruptions to this activity in J20 mice may underlie cognitive impairments seen in these animals. [ABSTRACT FROM AUTHOR]

Liver cancer ranks as the fourth leading cause of cancer-related deaths. Despite extensive research efforts aiming to evaluate the biological mechanisms underlying hepatocellular carcinoma (HCC) development, little has been translated towards new diagnostic and treatment options for HCC patients. Historically, the focus has been centered on coding RNAs and their respective proteins. However, significant advances in sequencing and RNA detection technologies have shifted the research focus towards non-coding RNAs (ncRNA), as well as their impact on HCC development and progression. A number of studies reported complex post-transcriptional interactions between various ncRNA and coding RNA molecules. These interactions offer insights into the role of ncRNAs in both the known pathways leading to oncogenesis, such as dysregulation of p53, and lesser-known mechanisms, such as small nucleolar RNA methylation. Studies investigating these mechanisms have identified prevalent ncRNA changes in microRNAs, snoRNAs, and long non-coding RNAs that can both pre- and post-translationally regulate key factors in HCC progression. In this review, we present relevant publications describing ncRNAs to summarize the impact of different ncRNA species on liver cancer development and progression and to evaluate recent attempts at clinical translation. [ABSTRACT FROM AUTHOR]

Ischemic stroke and cerebral amyloid angiopathy (CAA) pose significant challenges in an aging population, particularly in post-stroke recovery. Using the 5xFAD mouse model, we explore the relationship between CAA, ischemic stroke, and tissue recovery. We hypothesize that amyloid-beta accumulation worsens stroke outcomes by inducing blood-brain barrier (BBB) dysfunction, leading to impaired neurogenesis. Our findings show that CAA exacerbates stroke outcomes, with mice exhibiting constricted BBB microvessels, reduced cerebral blood flow, and impaired tissue recovery. Transcriptional analysis shows that endothelial cells and neural progenitor cells (NPCs) in the hippocampus exhibit differential gene expression in response to CAA and stroke, specifically targeting the phosphatidylinositol 3-kinase (PI3K) pathway. In vitro experiments with human NPCs validate these findings, showing that disruption of the CXCL12 - PIK3C2A - CREB3L2 axis impairs neurogenesis. Notably, PI3K pathway activation restores neurogenesis, highlighting a potential therapeutic approach. These results suggest that CAA combined with stroke induces microvascular dysfunction and aberrant neurogenesis through this specific pathway. [Display omitted] • Function and tissue recovery after ischemic stroke are significantly impaired in 5xFAD mice • Changes in the BBB reduce blood flow and reperfusion capability in the 5xFAD genotype • Transcriptomic analysis links endothelial cells and hippocampal NPCs via the PI3K pathway • Activation of the PI3K pathway rescues neurogenesis in 5xFAD mice post stroke Osborne et al. use the 5xFAD mouse model to show that cerebral amyloid angiopathy impairs stroke recovery by disrupting the interaction between blood-brain barrier endothelial cells and hippocampal NPCs. Mechanistically, they demonstrate that reactivating the PI3K/CREB pathway stimulates adult neurogenesis, suggesting potential therapeutic strategies to enhance tissue recovery post stroke. [ABSTRACT FROM AUTHOR]

Background: Cognitive health is of great interest to society, with neuroinflammation and systemic inflammation age-related risk factors that are linked to declines in cognitive performance. Several botanical ingredients have been suggested to have benefits in this area including Salvia officinalis (sage), which has shown anti-inflammatory effects and exhibited promising cognitive improvements in multiple human studies. The current study demonstrates anti-inflammatory effects for S. officinalis across a broad set of in vitro models in human cells, and adds further evidence to support modulation of acetylcholine and monoamine neurostransmitter levels as mechanisms that contribute towards the benefits of the herb on cognitive health. Methods: The effect of S. officinalis extract on release of multiple cytokines and chemokines was measured in human primary intestinal epithelial cells treated with or without LPS stimulation, and Blood Brain Barrier (BBB) cells in presence or absence of recombinant IL-17A and/or Human IL-17RA/IL-17R Antibody. Antioxidant effects were also assessed in BBB cells incubated with the extract and H2O2. The anti-inflammatory effects of S. officinalis extract were further assessed based on clinically-relevant biomarker readouts across 12 human primary cell-based disease models of the BioMAP Diversity PLUS panel. Results: S. officinalis showed significant attenuation of the release of most cytokines/chemokines into apical media in LPS-stimulated intestinal cells, but small increases in the release of markers including IL-6, IL-8 in basolateral media; where TNF-α was the only marker to be significantly reduced. S. officinalis attenuated the release of CRP and VCAM-1 from BBB cells under IL-17A induced conditions, and also decreased H2O2 induced ROS overproduction in these cells. Phenotypic profiling with the BioMAP Diversity PLUS Panel identified additional anti-inflammatory mediators, and based on a similarity search analysis suggested potential mechanistic similarity to caffeic acid and drugs known to inhibit COMT and MAO activity to modulate monoamine metabolism. Subsequent in vitro assessment showed that S. officinalis was able to inhibit the activity of these same enzymes. Conclusions: S. officinalis extract showed anti-inflammatory effects across multiple human cell lines, which could potentially reduce peripheral inflammation and support cognitive health. S. officinalis extract also showed the ability to inhibit enzymes related to the metabolism of monoamine neurotransmitters, suggesting possible dopaminergic and serotonergic effects acting alongside proposed cholinergic effects to mediate acute cognitive performance benefits previously demonstrated for the extract. [ABSTRACT FROM AUTHOR]

Background: Maternal nutrition influences fetal development and may permanently alter ("program") offspring body composition and metabolism, thereby influencing later risk of diabetes and cardiovascular (cardiometabolic) disease. The prevalence of cardiometabolic disease is rising rapidly in India.Objectives: To test the hypothesis that supplementing low-income Indian women with micronutrient-rich foods preconceptionally and during pregnancy has a beneficial impact on the children's body composition and cardiometabolic risk marker profiles.Methods: Follow-up of 1255 children aged 5-10 y whose mothers took part in the Mumbai Maternal Nutrition Project [Project "SARAS"; International Standard Randomised Controlled Trial Number (ISRCTN)62811278]. Mothers were randomly assigned to receive a daily micronutrient-rich snack or a control snack of lower micronutrient content, both made from local foods, in addition to normal diet, from before pregnancy until delivery. Children's body composition was assessed using anthropometry and DXA. Their blood pressure, plasma glucose, insulin, and lipid concentrations were measured. Outcomes were compared between allocation groups with and without adjustment for confounding factors.Results: Overall, 15% of children were stunted, 34% were wasted, and 3% were overweight. In the intention-to-treat analysis, there were no differences in body composition or risk markers between children in the intervention and control groups. Among children whose mothers started supplementation ≥3 mo before conception (the "per protocol" sample) the intervention increased adiposity among girls, but not boys. BMI in girls was increased relative to controls by 2% (95% CI: 1, 4; P = 0.01); fat mass index by 10% (95% CI: 3, 18; P = 0.004); and percent fat by 7% (95% CI: 1, 13; P = 0.01) unadjusted, with similar results in adjusted models.Conclusions: Overall, supplementing women with micronutrient-rich foods from before pregnancy until delivery did not alter body composition or cardiometabolic risk markers in the children. Subgroup analyses showed that, if started ≥3 mo before conception, supplementation may increase adiposity among female children. [ABSTRACT FROM AUTHOR]

This essay examines what AI can dofor government, specifically through three generic tools at the heart of governance: detection, prediction, and data-driven decision-making. Public sector functions, such as resource allocation and the protection of rights, are more normatively loaded than those of firms, and AI poses greater ethical challenges than earlier generations of digital technology, threatening transparency, fairness, and accountability. The essay discusses how AI might be developed specifically for government, with a public digital ethos to protect these values. Three moves that could maximize the transformative possibilities for a distinctively public sector AI are the development of government capacity to foster innovation through AI; the building of integrated and generalized models for policy-making; and the detection and tackling of structural inequalities. Combined, these developments could offer a model of data-intensive government that is more efficient, ethical, fair, prescient, and resilient than ever before in administrative history. [ABSTRACT FROM AUTHOR]

Background: Common Variable Immunodeficiency (CVID) is classified as a 'Predominantly Antibody Deficiency' (PAD), but there is emerging evidence of cellular immunodeficiency in a subset of patients. This evidence includes CVID patients diagnosed with cytomegalovirus (CMV) infection, a hallmark of 'combined immunodeficiency'. CMV infection also has the potential to drive immune dysregulation contributing to significant morbidity and mortality in CVID. We aim to determine the extent of cellular immune dysfunction in CVID patients, and whether this correlates with CMV infection status. Methods: We conducted a single-center retrospective cohort study of individuals with CVID at the Royal Melbourne Hospital, and identified patients with and without CMV disease or viraemia. We then isolated T-cells from patient and healthy donor blood samples and examined T-cell proliferation and function. Results: Six patients (7.6%, 6/79) had either CMV disease (pneumonitis or gastrointestinal disease), or symptomatic CMV viraemia. A high mortality rate in the cohort of patients with CVID and CMV disease was observed, with 4 deaths in the period of analysis (66.6%, 4/6). Individuals with CMV infection showed reduced T-cell division in response to T-cell receptor (TCR) stimulation when compared with CMV-negative patients. Discussion: This study demonstrates the morbidity and mortality associated with CMV in CVID, and highlights the need for focused interventions for patients with CVID at risk of CMV disease. [ABSTRACT FROM AUTHOR]

Deficiency of adenosine deaminase (ADA, EC3.5.4.4), a housekeeping enzyme intrinsic to the purine salvage pathway, leads to severe combined immunodeficiency (SCID) both in humans and mice. Lack of ADA results in the intracellular accumulation of toxic metabolites which have effects on T cell development and function. While untreated ADA-SCID is a fatal disorder, there are different therapeutic options available to restore ADA activity and reconstitute a functioning immune system, including enzyme replacement therapy (ERT). Administration of ERT in the form of pegylated bovine ADA (PEG-ADA) has proved a life-saving though non-curative treatment for ADA-SCID patients. However, in many patients treated with PEG-ADA, there is suboptimal immune recovery with low T and B cell numbers. Here, we show reduced thymus cellularity in ADA-SCID mice despite weekly PEG-ADA treatment. This was associated with lack of effective adenosine (Ado) detoxification in the thymus. We also show that thymocyte development in ADA-deficient thymi is arrested at the DN3-to-DN4 stage transition with thymocytes undergoing dATP-induced apoptosis rather than defective TCRβ rearrangement or β-selection. Our studies demonstrate at a detailed level that exogenous once-a-week enzyme replacement does not fully correct intra-thymic metabolic or immunological abnormalities associated with ADA deficiency. [ABSTRACT FROM AUTHOR]

Deficiency of adenosine deaminase (ADA, EC3.5.4.4), a housekeeping enzyme intrinsic to the purine salvage pathway, leads to severe combined immunodeficiency (SCID) both in humans and mice. Lack of ADA results in the intracellular accumulation of toxic metabolites which have effects on T cell development and function. While untreated ADA-SCID is a fatal disorder, there are different therapeutic options available to restore ADA activity and reconstitute a functioning immune system, including enzyme replacement therapy (ERT). Administration of ERT in the form of pegylated bovine ADA (PEG-ADA) has proved a life-saving though non-curative treatment for ADA-SCID patients. However, in many patients treated with PEG-ADA, there is suboptimal immune recovery with low T and B cell numbers. Here, we show reduced thymus cellularity in ADA-SCID mice despite weekly PEG-ADA treatment. This was associated with lack of effective adenosine (Ado) detoxification in the thymus. We also show that thymocyte development in ADA-deficient thymi is arrested at the DN3-to-DN4 stage transition with thymocytes undergoing dATP-induced apoptosis rather than defective TCRβ rearrangement or β-selection. Our studies demonstrate at a detailed level that exogenous once-a-week enzyme replacement does not fully correct intra-thymic metabolic or immunological abnormalities associated with ADA deficiency. [ABSTRACT FROM AUTHOR]

Recent high-profile collapses coupled with an aging bridge stock, increased loading, and the pressures of climate change have led to a greater focus on bridge management by policymakers. To prevent any negative socioeconomic impacts, timely inspection of bridges becomes of prime importance. Visual inspection is standard practice around the world but is subjective in nature and is influenced by many factors that can affect the accuracy of results and future decisions. The research presented here critically compares the conventional visual inspection approach with a virtual reality (VR) inspection technique that combines Lidar and VR, applied for the first time to bridges made of reinforced concrete. Inspection of the Mancunian Way, an elevated motorway in Manchester, UK, is performed by the conventional visual approach and the VR approach. Digital virtual twins of the bridge are developed. Lidar is used to capture a 3D image of the geometric surface of the bridge incorporating all its defects. The image is postprocessed and a VR application is created using Unity, a software development kit, for inspection of bridges in an immersive 3D virtual environment. The resulting VR app is evaluated subjectively by conducting a critical comparison between both methods. The results demonstrate promising improvements over the conventional inspection technique. It is intended that this research will benefit civil engineers in inspecting bridges as well as policymakers who may revise bridge inspection codes and procedures. [ABSTRACT FROM AUTHOR]

Introduction: Sudden unexpected death in infancy (SUDI) represents the commonest presentation of postneonatal death. We explored whether machine learning could be used to derive data driven insights for prediction of infant autopsy outcome. Methods: A paediatric autopsy database containing >7,000 cases, with >300 variables, was analysed by examination stage and autopsy outcome classified as 'explained (medical cause of death identified)' or 'unexplained'. Decision tree, random forest, and gradient boosting models were iteratively trained and evaluated. Results: Data from 3,100 infant and young child (<2 years) autopsies were included. Naïve decision tree using external examination data had performance of 68% for predicting an explained death. Core data items were identified using model feature importance. The most effective model was XG Boost, with overall predictive performance of 80%, demonstrating age at death, and cardiovascular and respiratory histological findings as the most important variables associated with determining medical cause of death. Conclusion: This study demonstrates feasibility of using machine-learning to evaluate component importance of complex medical procedures (paediatric autopsy) and highlights value of collecting routine clinical data according to defined standards. This approach can be applied to a range of clinical and operational healthcare scenarios [ABSTRACT FROM AUTHOR]

It is intriguing that, unlike adults with HIV-1, children with HIV-1 reach a greater CD4+ T cell recovery following planned treatment cessation. The reasons for the better outcomes in children remain unknown but may be related to increased thymic output and diversity of T cell receptor repertoires. HIV-1 infected children from the PENTA 11 trial tolerated planned treatment interruption without adverse long-term clinical, virological, or immunological consequences, once antiretroviral therapy was re-introduced. This contrasts to treatment interruption trials of HIV-1 infected adults, who had rapid changes in T cells and slow recovery when antiretroviral therapy was restarted. How children can develop such effective immune responses to planned treatment interruption may be critical for future studies. PENTA 11 was a randomized, phase II trial of planned treatment interruptions in HIV-1-infected children (ISRCTN 36694210). In this sub-study, eight patients in long-term follow-up were chosen with CD4+ count>500/ml, viral load <50c/ml at baseline: four patients on treatment interruption and four on continuous treatment. Together with measurements of thymic output, we used high-throughput next generation sequencing and bioinformatics to systematically organize memory CD8+ and naïve CD4+ T cell receptors according to diversity, clonal expansions, sequence sharing, antigen specificity, and T cell receptor similarities following treatment interruption compared to continuous treatment. We observed an increase in thymic output following treatment interruption compared to continuous treatment. This was accompanied by an increase in T cell receptor clonal expansions, increased T cell receptor sharing, and higher sequence similarities between patients, suggesting a more focused T cell receptor repertoire. The low numbers of patients included is a limitation and the data should be interpreted with caution. Nonetheless, the high levels of thymic output and the high diversity of the T cell receptor repertoire in children may be sufficient to reconstitute the T cell immune repertoire and reverse the impact of interruption of antiretroviral therapy. Importantly, the effective T cell receptor repertoires following treatment interruption may inform novel therapeutic strategies in children infected with HIV-1. [ABSTRACT FROM AUTHOR]