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Atherosclerosis is a complex inflammatory disease in which the adaptive immune response plays an important role. While the overall impact of T and B cells in atherosclerosis is relatively well established, we are only beginning to understand how bidirectional T-cell/B-cell interactions can exert prominent atheroprotective and proatherogenic functions. In this review, we will focus on these T-cell/B-cell interactions and how we could use them to therapeutically target the adaptive immune response in atherosclerosis.

A convergent route toward nitrogen-bridged BODIPY oligomers has been developed. The synthetic key step is a Buchwald–Hartwig cross-coupling reaction of an α-amino-BODIPY and the respective halide. Not only does the selective synthesis provide control of the oligomer size, but the facile preparative procedure also enables easy access to these types of dyes. Furthermore, functionalized examples were accessible via brominated derivatives.

People exposed to more unfavourable social circumstances are more vulnerable to poor mental health over their life course, in ways that are often determined by structural factors which generate and perpetuate intergenerational cycles of disadvantage and poor health. Addressing these challenges is an imperative matter of social justice. In this paper we provide a roadmap to address the social determinants that cause mental ill health. Relying as far as possible on high‐quality evidence, we first map out the literature that supports a causal link between social determinants and later mental health outcomes. Given the breadth of this topic, we focus on the most pervasive social determinants across the life course, and those that are common across major mental disorders. We draw primarily on the available evidence from the Global North, acknowledging that other global contexts will face both similar and unique sets of social determinants that will require equitable attention. Much of our evidence focuses on mental health in groups who are marginalized, and thus often exposed to a multitude of intersecting social risk factors. These groups include refugees, asylum seekers and displaced persons, as well as ethnoracial minoritized groups; lesbian, gay, bisexual, transgender and queer (LGBTQ+) groups; and those living in poverty. We then introduce a preventive framework for conceptualizing the link between social determinants and mental health and disorder, which can guide much needed primary prevention strategies capable of reducing inequalities and improving population mental health. Following this, we provide a review of the evidence concerning candidate preventive strategies to intervene on social determinants of mental health. These interventions fall broadly within the scope of universal, selected and indicated primary prevention strategies, but we also briefly review important secondary and tertiary strategies to promote recovery in those with existing mental disorders. Finally, we provide seven key recommendations, framed around social justice, which constitute a roadmap for action in research, policy and public health. Adoption of these recommendations would provide an opportunity to advance efforts to intervene on modifiable social determinants that affect population mental health.

All-atom molecular dynamics (MD) simulations are an essential structural biology technique with increasing application to multimillion-atom systems, including viruses and cellular machinery. Classical MD simulations rely on parameter sets, such as the AMBER family of force fields (AMBERff), to accurately describe molecular motion. Here, we present an implementation of AMBERff for use in NAMD that overcomes previous limitations to enable high-performance, massively parallel simulations encompassing up to two billion atoms. Single-point potential energy comparisons and case studies on model systems demonstrate that the implementation produces results that are as accurate as running AMBERff in its native engine.

The rising prevalence and legalisation of cannabis worldwide have underscored the need for a comprehensive understanding of its biological impact, particularly on mental health. Epigenetic mechanisms, specifically DNA methylation, have gained increasing recognition as vital factors in the interplay between risk factors and mental health. This study aimed to explore the effects of current cannabis use and high-potency cannabis on DNA methylation in two independent cohorts of individuals experiencing first-episode psychosis (FEP) compared to control subjects. The combined sample consisted of 682 participants (188 current cannabis users and 494 never users). DNA methylation profiles were generated on blood-derived DNA samples using the Illumina DNA methylation array platform. A meta-analysis across cohorts identified one CpG site (cg11669285) in the CAVIN1gene that showed differential methylation with current cannabis use, surpassing the array-wide significance threshold, and independent of the tobacco-related epigenetic signature. Furthermore, a CpG site localised in the MCUgene (cg11669285) achieved array-wide significance in an analysis of the effect of high-potency (THC = > 10%) current cannabis use. Pathway and regional analyses identified cannabis-related epigenetic variation proximal to genes linked to immune and mitochondrial function, both of which are known to be influenced by cannabinoids. Interestingly, a model including an interaction term between cannabis use and FEP status identified two sites that were significantly associated with current cannabis use with a nominally significant interaction suggesting that FEP status might moderate how cannabis use affects DNA methylation. Overall, these findings contribute to our understanding of the epigenetic impact of current cannabis use and highlight potential molecular pathways affected by cannabis exposure.

Living systems carry out the reduction of N2to ammonia (NH3) through a series of protonation and electron transfer steps under ambient conditions using the enzyme nitrogenase. In the chemical industry, the Haber–Bosch process hydrogenates N2but requires high temperatures and pressures. Both processes rely on iron-based catalysts, but molecular iron complexes that promote the formation of NH3on addition of H2to N2have remained difficult to devise. Here, we isolate the tri(iron)bis(nitrido) complex [(Cp′Fe)3(μ3-N)2] (in which Cp′ = η5-1,2,4-(Me3C)3C5H2), which is prepared by reduction of [Cp′Fe(μ-I)]2under an N2atmosphere and comprises three iron centres bridged by two μ3-nitrido ligands. In solution, this complex reacts with H2at ambient temperature (22 °C) and low pressure (1 or 4 bar) to form NH3. In the solid state, it is converted into the tri(iron)bis(imido) species, [(Cp′Fe)3(μ3-NH)2], by addition of H2(10 bar) through an unusual solid–gas, single-crystal-to-single-crystal transformation. In solution, [(Cp′Fe)3(μ3-NH)2] further reacts with H2or H+to form NH3.

MSCs and MSC-derived secretory factors, including Annexin A1, reduce EC activation.MSCs and MSC-secretory factors reduce islet expression of pro-inflammatory chemokines.MSCs and MSC-secretory factors reduce inflammatory crosstalk between islets and ECs.

As the summary narrative introducing the comprehensive annual financial report (CAFR) issued by state or local governments in the U.S., the Management's Discussion and Analysis (MD&A) is intended to facilitate meaningful use by a broad audience. The MD&A serves as a transparency mechanism and must be accessible in terms of size, readability, and timeliness. We examine accessibility of MD&As issued by state governments in the U.S. using institutional, agency, and legitimacy theories to analyze how accessibility is related to internal (organizational) and external (environmental) factors. Our findings offer support for the importance of internal factors. The lack of support for institutional, agency, or legitimacy theory imply the lack of intentionality by states to go beyond required content to bolster accessibility for the non-expert public user.Points for practitioners• Accessibility of the Management's Discussion and Analysis (MD&A) can be measured using three dimensions: size, readability, and timeliness.• States with an elected comptroller had more accessible MD&As, suggesting that an elected comptroller, serving as the chief fiscal officer, may be more responsive to public demands compared to a political appointee.• Organizational capacity factors were most influential in explaining timeliness of MD&A issuance, with greater capacity being reflected in more spending on central agency staff and greater number of state employees.

A multigram scale synthetic procedure for the preparation of a complex and polar macrocyclic peptidic C5aR antagonist is described. The route was developed through improvements to an initial small-scale research synthesis and hinged on optimized solid-phase peptide synthesis featuring an early side chain decoration, a highly efficient off-resin macrolactamization, and global deprotection steps. These improvements resulted in a reduction in off-resin peptide manipulations and ultimately to a 6-fold increase in overall yield from 2-chlorotrityl-bound intermediate SP-7c.

AbstractThe application and provision of prehospital care in disasters and mass-casualty incident response in Europe is currently being explored for opportunities to improve practice. The objective of this translational science study was to align common principles of approach and action and to identify how technology can assist and enhance response. To achieve this objective, the application of a modified Delphi methodology study based on statements derived from key findings of a scoping review was undertaken. This resulted in 18 triage, eight life support and damage control interventions, and 23 process consensus statements. These findings will be utilized in the development of evidence-based prehospital mass-casualty incident response tools and guidelines.

ABSTRACTThis article uses a human geography approach to explore, and reflect upon, the ways in which some of the leading supermarket retailers in Europe are addressing the transition to net-zero greenhouse gas emissions.

Both general purpose local governments and special districts accumulate and drain fiscal reserves to prepare for and respond to financial uncertainty. Whether or not fiscal reserves behavior are subject to isomorphic pressures is an emerging question in the literature. While multiple papers have provided evidence of a single isomorphic pressure, no paper has separately tested for three distinct isomorphic pressures in the fiscal reserves literature. With a panel dataset of Kentucky school districts from 2004 to 2019, this article uses descriptive and inferential methods to provide evidence of coercive, normative, and mimetic isomorphic pressures. Collectively, these findings not only build the literature on special districts but call into question the role of normative pressures from the Government Finance Officers Association and coercive pressures from state-imposed fiscal reserve rules.

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Studies conducted in psychotic disorders have shown that DNA-methylation (DNAm) is sensitive to the impact of Childhood Adversity (CA). However, whether it mediates the association between CA and psychosis is yet to be explored. Epigenome wide association studies (EWAS) using the Illumina Infinium-Methylation EPIC array in peripheral blood tissue from 366 First-episode of psychosis and 517 healthy controls was performed. Adversity scores were created for abuse, neglect and composite adversity with the Childhood Trauma Questionnaire (CTQ). Regressions examining (I) CTQ scores with psychosis; (II) with DNAm EWAS level and (III) between DNAm and caseness, adjusted for a variety of confounders were conducted. Divide-Aggregate Composite-null Test for the composite null-hypothesis of no mediation effect was conducted. Enrichment analyses were conducted with missMethylpackage and the KEGG database. Our results show that CA was associated with psychosis (Composite: OR = 1.68; p= <0.001; abuse: OR = 2.16; p< 0.001; neglect: OR = 2.27; p= <0.001). None of the CpG sites significantly mediated the adversity-psychosis association after Bonferroni correction (p< 8.1 × 10−8). However, 28, 34 and 29 differentially methylated probes associated with 21, 27, 20 genes passed a less stringent discovery threshold (p< 5 × 10−5) for composite, abuse and neglect respectively, with a lack of overlap between abuse and neglect. These included genes previously associated to psychosis in EWAS studies, such as PANK1, SPEG TBKBP1, TSNARE1 or H2R. Downstream gene ontology analyses did not reveal any biological pathways that survived false discovery rate correction. Although at a non-significant level, DNAm changes in genes previously associated with schizophrenia in EWAS studies may mediate the CA-psychosis association. These results and associated involved processes such as mitochondrial or histaminergic disfunction, immunity or neural signalling requires replication in well powered samples. The lack of overlap between mediating genes associated with abuse and neglect suggests differential biological trajectories linking CA subtypes and psychosis.

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Over the past thirty years, four surveys have analyzed local government forecast practices, with the most recent being over a decade old. This article builds on the prior surveys with a novel 2018 survey dataset from the Government Finance Officers Association to examine the factors related to the adoption of a particular forecast time horizon and the perceived influence of forecasts on the final adopted budget. Estimates of ordered logistic regressions with predictive margins indicate that certain budget processes and the length of time since a government adopted a new budget process are associated with forecast practices.

Review of: Beyond the Streets, Roger Gastman (Ed.) (2023)London: Beyond the Streets and Saatchi Gallery, 585 pp.,ISBN 978-0-57846-883-9, h/bk, £70

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Quantum atomic technologies, such as optical clocks and atom interferometers, have demonstrated their potential in laboratory settings; however, their widespread deployment for real-world applications requires significant improvement in their size, weight, power, and cost (SWaP-C). We have fabricated compact laser avionics suitable for laser cooling and spectroscopy applications. The system employs a commercial laser diode, fiber-coupled optics, current and temperature controllers, analog-to-digital converters (ADCs), and all-digital signal processing, and operates on a single 5-V power supply. Using these components, a 780-nm laser has been stabilized to the Rb D2 transition via frequency modulation (FM) spectroscopy, with a SWaP budget of 1 L, 300 g, and less than 10 W. Due to its modular design and digital reprogrammability, the low-SWaP-C system developed here can be applied to devices across the quantum technology sector.

Substance use disorders constitute a major global public health problem, attributable largely to their subsequent comorbidity with other health conditions. This study aimed to investigate the risk of all-cause death and life-years lost following hospitalisation for 28 subsequent physical comorbid conditions in people with a previous hospitalisation for substance use disorder, compared with matched counterparts without substance use disorder.

The reactivity of 1,1′-bis(3-methyl-4-imidazolin-2-selone)methane (L1) and 1,2-bis(3-methyl-4-imidazolin-2-selone)ethane (L2) toward I2has been explored in MeCN under different experimental conditions and compared with that in CH2Cl2. The compounds [L1′](I)2(I), [L1I]n(I)n(II), [L1(μ-Se)](I)2·1/2H2O (III), [L1I](I3)·2I2(IV), and [L2](I)2·MeCN (V) were obtained and characterized. X-ray diffraction analyses point out an ionic nature for these compounds, which is presumably favored by the polarity of the solvent used. In particular, [L1I]n(I)n(II) represents the first example of an iodonium complex of imidazoline-2-selone derivatives, while [L1(μ-Se)](I)2·1/2H2O (III) represents a unique example of a dicationic [RSeSeSeR] triselane. Density functional theory calculations have allowed us to better understand the nature of the obtained compounds and to justify their formations in polarizing reaction conditions rather than in low polar solvents.

Review of: 69 Exhibition Road: Twelve True-Life Tales from the Fag End of Punk, Porn & Performance, Dorothy Max Prior (2022)London: Strange Attractor Press, 328 pp.,ISBN 978-1-91368-963-6, p/bk, £18.99The Horror Show! A Twisted Tale of Modern Britain, Faye Dowling (Ed.) (2022)London: Somerset House Trust, 128 pp.,ISBN 987-1-99961-549-9, p/bk, £16.50

AbstractBackgroundNonsuicidal self-injury (NSSI) is prevalent among adolescents and research is needed to clarify the mechanisms which contribute to the behavior. Here, the authors relate behavioral neurocognitive measures of impulsivity and compulsivity to repetitive and sporadic NSSI in a community sample of adolescents.MethodsComputerized laboratory tasks (Affective Go/No-Go, Cambridge Gambling Task, and Probabilistic Reversal Task) were used to evaluate cognitive performance. Participants were adolescents aged 15 to 17 with (n = 50) and without (n = 190) NSSI history, sampled from the ROOTS project which recruited adolescents from secondary schools in Cambridgeshire, UK. NSSI was categorized as sporadic (1-3 instances per year) or repetitive (4 or more instances per year). Analyses were carried out in a series of linear and negative binomial regressions, controlling for age, gender, intelligence, and recent depressive symptoms.ResultsAdolescents with lifetime NSSI, and repetitive NSSI specifically, made significantly more perseverative errors on the Probabilistic Reversal Task and exhibited significantly lower quality of decision making on the Cambridge Gambling Task compared to no-NSSI controls. Those with sporadic NSSI did not significantly differ from no-NSSI controls on task performance. NSSI was not associated with behavioral measures of impulsivity.ConclusionsRepetitive NSSI is associated with increased behavioral compulsivity and disadvantageous decision making, but not with behavioral impulsivity. Future research should continue to investigate how neurocognitive phenotypes contribute to the onset and maintenance of NSSI, and determine whether compulsivity and addictive features of NSSI are potential targets for treatment.

The United Nations Sustainable Development Goals (SDGs) are universally seen to be global in their nature and reach, but there is a growing acceptance that they have an important local dimension. At the same time, there is an increasing recognition of the need for appropriate Information and Communication Technologies (ICTs) to support and monitor the SDGs. This article adopts a qualitative inductive research approach in examining a range of public authority and academic source material, and framework analysis is used to record, categorise and critique this material. The findings provide an overview of the role of the SDGs at the local level and an assessment of how the localisation of the SDGs is being addressed in some urban areas within Western Europe. The findings also indicate how ICTs are being deployed to support the localisation process in Western Europe and the wider world. This is followed by a discussion of some emergent issues related to the localisation of the SDGs, including the increasingly important role of ICTs.

The causes of a pyrexia of unknown origin (PUO) are broadly spread across infectious, malignant, or inflammatory conditions. The authors report a case of a 43-year-old female who initially presented with hypoxia and fevers secondary to a presumed acute viral or bacterial infectious pulmonary insult. However, fevers persisted despite pulmonary imaging remaining normal. The case subsequently evolved into a PUO with multiple lines of investigation proving inconclusive. No definitive diagnosis was made at the time of discharge; however, cessation of hydralazine was noted to coincide with the last of the patient’s fevers. Following the discharge, her anti-histone antibodies returned a positive result, and the diagnosis of drug-induced lupus was made with hydralazine as the presumed trigger.