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Plotinus' Enneads is a work which is central to the history of philosophy in late antiquity. This is the second edition of the first English translation of the complete works of Plotinus in one volume in seventy years, which also includes Porphyry's Life of Plotinus. Led by Lloyd P. Gerson, a team of experts present up-to-date translations which are based on the best available text, the edition minor of Henry and Schwyzer and its corrections. The translations are consistent in their vocabulary, making the volume ideal for the study of Plotinus' philosophical arguments. This second edition includes a number of corrections, as well as additional cross-references to enrich the reader's understanding of Plotinus' sometimes very difficult presentation of his ideas. It will be invaluable for scholars of Plotinus with or without ancient Greek, as well as for students of the Platonic tradition.
Aims: The UK Biobank is a large-scale prospective cohort study with data collected on over 500,000 individuals within the United Kingdom. We sought to understand whether the years around the menopause are associated with an increased likelihood of depressive symptoms, using the PHQ-2 questionnaire, which screens for depressive disorders. A score of 3 or above is suggestive of a depressive disorder. Our analysis looked at the likelihood of having significant depressive symptoms in the years before and after the final menstrual period.
Methods: Exclusion criteria included male participants, participants who had bilateral oophorectomies, those who were unsure of when their FMP was due to having a hysterectomy, those whose age at final menstrual period was under 40 or preferred not to say, and those whose reported age at final menstrual period differed by >2 years when asked on different occasions. Participants who did not give an answer to either of the two screening questions were also excluded.
The PHQ-2 enquires about depressive mood and anhedonia over the prior two weeks at baseline assessment. Possible answers were not at all, several days, more than half the days, and nearly every day. Using logistic regression, odds ratios were calculated for likelihood of having a PHQ-2 score above 3 from 9 years prior to the final menstrual period to 9 years after, compared with the year of the final menstrual period.
Results: In females undergoing natural menopause (n=143,685) those assessed who were within a year of their final menstrual period had the highest rate of depressive symptoms. 7.6% of women within a year of their final menstrual period had a PHQ-2 score of 3 or more. Depressive symptoms at all other timepoints were less frequent, ranging from 3.9% to 7.1%, with the OR compared with year of final menstrual period ranging between 0.49 to 0.93. In the 2 years either side of the final menstrual period, depressive symptoms were not significantly lower than the year of the final menstrual period, particularly at 2 years prior (6.0%, OR 0.77 (95% CI (0.58, 1.02)), one year post (6.9%, OR 0.90 (95% CI (0.78, 1.05)) and 2 years post (7.1%, OR 0.93 (95% CI (0.80, 1.08)).
Conclusion: These results suggest that the proportion of women experiencing significant depressive symptoms increases in the years around the final menstrual period. There is an increased likelihood of significant depressive symptoms in the year of the final menstrual period compared with surrounding years.
The crystal structure of delamanid has been solved and refined using synchrotron X-ray powder diffraction data and optimized using density functional theory techniques. Solution and refinement of the structure presented significant difficulties, and the result should be considered proposed or approximate. Delamanid crystallizes in the space group P212121 (#19) with a = 67.3701(18), b = 12.86400(9), c = 5.65187(12) Å, V = 4,898.19(14) Å3, and Z = 8 at 295 K. There are two independent delamanid molecules, with different conformations, which are essentially identical in energy. The crystal structure consists of layers of delamanid molecules perpendicular to the a-axis. The imidazooxazole ring systems stack along the b-axis, and the trifluoromethyl groups make up the boundaries of the corrugated layers. There are no classical hydrogen bonds in the crystal structure. Eight C–H···O and one C–H···N hydrogen bonds contribute to the lattice energy. The powder pattern has been submitted to the International Centre for Diffraction Data for inclusion in the Powder Diffraction File™ (PDF®).
We report the lattice parameters and cell volume for cristobalite powder added at 35 wt% to Ba-Al-Silicate glass (CGI930) as reflowed bulk glass bars where the embedded cristobalite phase is constrained within the glass matrix. Analysis confirms that the room temperature lattice parameters and cell volume obtained for the bulk glass–ceramic are larger compared with single-phase cristobalite powders. The increased volume of the cristobalite phase in a glass matrix is driven by tensile stresses developed at the interface between the cristobalite and matrix glass phase, and this stress impacts the phase transition temperature and thermal hysteresis of the cristobalite phase. In situ high-temperature measurements confirm that the tetragonal to cubic α–β phase transformation of the cristobalite phase within the glass matrix is ~195 °C with complete suppression of hysteresis behavior. In contrast, bulk glass–ceramic material ground to a powder form displays the expected thermal hysteresis behavior and more comparable phase transition temperatures of 245 °C on heating and 220 °C on cooling. Isothermal holds at varying temperatures above or near the α–β phase transition suggest that the cristobalite phase does not undergo significant relaxation within the matrix phase to reduce accumulated stress imposed by the constraining matrix glassy phase.
The First Large Absorption Survey in H i (FLASH) is a large-area radio survey for neutral hydrogen in and around galaxies in the intermediate redshift range 0.4 < z < 1.0, using the 21-cm H i absorption line as a probe of cold neutral gas. The survey uses the ASKAP radio telescope and will cover 24,000 deg2 of sky over the next five years. FLASH breaks new ground in two ways – it is the first large H i absorption survey to be carried out without any optical preselection of targets, and we use an automated Bayesian line-finding tool to search through large datasets and assign a statistical significance to potential line detections. Two Pilot Surveys, covering around 3000 deg2 of sky, were carried out in 2019-22 to test and verify the strategy for the full FLASH survey. The processed data products from these Pilot Surveys (spectral-line cubes, continuum images, and catalogues) are public and available online. In this paper, we describe the FLASH spectral-line and continuum data products and discuss the quality of the H i spectra and the completeness of our automated line search. Finally, we present a set of 30 new H i absorption lines that were robustly detected in the Pilot Surveys, almost doubling the number of known H i absorption systems at 0.4 < z < 1. The detected lines span a wide range in H i optical depth, including three lines with a peak optical depth τ > 1, and appear to be a mixture of intervening and associated systems. Interestingly, around two-thirds of the lines found in this untargeted sample are detected against sources with a peaked-spectrum radio continuum, which are only a minor (5-20%) fraction of the overall radio-source population. The detection rate for H i absorption lines in the Pilot Surveys (0.3 to 0.5 lines per 40 deg2 ASKAP field) is a factor of two below the expected value. One possible reason for this is the presence of a range of spectral-line artefacts in the Pilot Survey data that have now been mitigated and are not expected to recur in the full FLASH survey. A future paper in this series will discuss the host galaxies of the H i absorption systems identified here.
Neuropsychiatry training in the UK currently lacks a formal scheme or qualification, and its demand and availability have not been systematically explored. We conducted the largest UK-wide survey of psychiatry trainees to examine their experiences in neuropsychiatry training.
Results
In total, 185 trainees from all UK training regions completed the survey. Although 43.6% expressed interest in a neuropsychiatry career, only 10% felt they would gain sufficient experience by the end of training. Insufficient access to clinical rotations was the most common barrier, with significantly better access in London compared with other regions. Most respondents were in favour of additional neurology training (83%) and a formal accreditation in neuropsychiatry (90%).
Clinical implications
Strong trainee interest in neuropsychiatry contrasts with the limited training opportunities currently available nationally. Our survey highlights the need for increased neuropsychiatry training opportunities, development of a formalised training programme and a clinical accreditation pathway for neuropsychiatry in the UK.
Whilst thoracic myelopathy secondary to degenerative disease is relatively uncommon, left untreated it carries significant morbidity. It is thus of critical importance that patients are correctly diagnosed and managed expediently and effectively. Unfortunately, the management of thoracic myelopathy can be challenging, not least due to the technical difficulty accessing the site of compression and indeed optimum management is also debated. In this Element the authors present background, clinical features, diagnosis, and pitfalls and then a handy management algorithm for this critical neurosurgical condition.
Microbial, anoxygenic phototrophic ferrous iron (Fe(II)) oxidation (pFeOx) plays an important role in biological iron cycling. The uptake and oxidation of dissolved Fe(II) species (Fe2+aq) as an electron donor for pFeOx bacteria is well understood. In contrast, the oxidation of solid Fe(II)-bearing minerals by pFeOx is less well studied, with possible mechanisms including dissolution of the minerals followed by uptake and intracellular oxidation of Fe2+aq or extracellular electron transfer from solid Fe(II) minerals to the bacterial cells. We investigated the oxidation of the Fe(II)-bearing carbonate mineral siderite (FeCO3) by an anoxygenic phototrophic Fe(II) oxidiser Rhodopseudomonas palustris TIE-1. We aimed to explain if oxidation was controlled by chemical dissolution kinetics or whether direct electron transfer was involved. Controlled dissolution experiments using increasing dissolved bicarbonate concentrations (0–300 mM HCO3–), supported by geochemical modelling, demonstrated that R. palustris TIE-1 can oxidise up to 5-fold more Fe(II) when cells are in direct contact with siderite than would be expected if oxidation occurred through dissolution alone. These results suggest that anoxygenic phototrophic Fe(II)-oxidising bacteria have the capability to enhance carbonate dissolution or even access solid-phase Fe(II) in siderite as a source of electrons, especially when siderite dissolution is limited or suppressed by geochemical constraints.
Community-engaged research is essential to advance the implementation of evidence-based practices, but engagement quality is rarely assessed. We evaluated community health centers’ (CHCs) experiences partnering with the Implementation Science Center for Cancer Control Equity (ISCCCE) using an online survey of 59 CHC staff. Of 38 respondents (64.4% response rate), most perceived their engagement positively, with over 92% feeling respected by ISCCCE collaborators and perceiving projects as beneficial. Limited staff time and resources were the main challenges identified. This study suggests the utility of gathering feedback to evaluate community research engagement and inform adaptations of research processes to optimize partnership quality.
Moral injury is a potentially deleterious mental health outcome that can follow exposure to events that challenge one’s moral code. Theoretical models suggest a multi-faceted self-concept may support adaptation following such events. However, little is known about the relationship between self-concept complexity and outcomes following potentially morally injurious events.
Aims:
This cross-sectional study investigated hypothesized relationships between self-concept complexity and outcomes in adults (n=172) exposed to potentially morally injurious events.
Method:
Participants completed validated measures of event-related distress, traumatic stress, depression and anxiety, and a self-complexity task in which they provided multiple descriptors of their self-concept. Responses were coded for overall diversity, defined as number of categories of self-descriptors, and role diversity, defined as number of social and activity-based roles.
Results:
Multiple regression analyses found greater role diversity independently predicted lower event-related distress, while overall self-diversity and total number of self-descriptors did not.
Conclusion:
Findings indicate diversity in active facets of the self (e.g. relational or activity-based roles) may buffer the effects of a potentially morally injurious event.
Mood and anxiety disorders co-occur and share symptoms, treatments and genetic risk, but it is unclear whether combining them into a single phenotype would better capture genetic variation. The contribution of common genetic variation to these disorders has been investigated using a range of measures; however, the differences in their ability to capture variation remain unclear, while the impact of rare variation is mostly unexplored.
Aims
We aimed to explore the contributions of common genetic variation and copy number variations associated with risk of psychiatric morbidity (P-CNVs) to different measures of internalising disorders.
Method
We investigated eight definitions of mood and anxiety disorder, and a combined internalising disorder, derived from self-report questionnaires, diagnostic assessments and electronic healthcare records (EHRs). Association of these definitions with polygenic risk scores (PRSs) of major depressive disorder and anxiety disorder, as well as presence of a P-CNV, was assessed.
Results
The effect sizes of both PRSs and P-CNVs were similar for mood and anxiety disorder. Compared to mood and anxiety disorder, internalising disorder resulted in higher prediction accuracy for PRSs, and increased significance of associations with P-CNVs for most definitions. Comparison across the eight definitions showed that PRSs had higher prediction accuracy and effect sizes for stricter definitions, whereas P-CNVs were more strongly associated with EHR- and self-report-based definitions.
Conclusions
Future studies may benefit from using a combined internalising disorder phenotype, and may need to consider that different phenotype definitions may be more informative depending on whether common or rare variation is studied.
There is a lack of ethical triage and treatment guidelines for the entrapped and mangled extremity (E&ME) in resource scarce environments: mass casualty incidents, low- to middle- income countries, complex humanitarian emergencies including conflict, and prolonged transport times (RSE).
Objectives:
The aim of this study is to use a modified Delphi (mD) approach to produce statements to develop treatment guidelines of the E&ME in RSE to advance the 2021 WHO EMT Minimum Standards (EMT) treating the E&ME.
Method/Description:
Experts rated their agreement with each statement on a 7- point linear numeric scale. Consensus amongst experts was defined as a standard deviation <= 1. Statements attaining consensus after the first round moved to the final report. Those not attaining consensus moved to the second round in which experts were shown the mean response of the expert panel and their own response for the opportunity to reconsider their rating for that round. Statements attaining consensus after the second round moved to the final report. This process repeated in the third round. Statements attaining consensus moved to the final report. The remaining statements did not attain consensus.
Results/Outcomes:
Seventy-seven experts participated in the first, 75 in the second, and 74 in the third round. Twenty-three statements attained consensus. Twenty-one statements did not attain consensus.
Conclusion:
A Delphi technique was used to establish consensus regarding the numerous complex factors influencing treatment of the E&ME in RSEs. Twenty-three statements attained consensus and can be incorporated into guidelines to advance the EMT treating the E&ME.
Chemical, biological, radiological, and nuclear (CBRN) incidents pose increasing transborder risks globally, necessitating enhanced health sector preparedness.
Objectives:
This study aimed to develop a comprehensive CBRN preparedness assessment tool (PAT), operational response guidelines (ORG), and tabletop simulation scenarios for the health sectors of the Middle East and North Africa (MENA) region.
Method/Description:
A mixed-methods approach comprised a systematic review of the literature up to 2022 in English and French, modified expert interviews (MIM), and an online Delphi questionnaire. Content analysis was performed on interview data. Using R-Studio™, consensus metrics and artificial intelligence techniques, including natural language processing, sentiment analysis, and unsupervised machine learning (ML) clustering algorithms, were deployed for advanced data analysis across all phases.
Results/Outcomes:
The literature review identified 63 relevant studies illustrating various preparedness strategies. The MIM’s thematic analysis, reinforced by AI-driven content analysis, emphasized the need for stronger inter-regional cooperation facilitated by organizations such as WHO and standardized tabletop simulation training. A robust consensus was achieved on the proposed assessment tool and operational response guidelines. ML analysis identified distinct expert clusters, providing additional consensus perspectives.
Conclusion:
The study emphasized the urgency for collaborative CBRN response strategies within MENA, valuing the innovative aspect of our suggested PAT, ORG, and simulation scenarios. This work advocates a dynamic, resilient approach to disaster medicine preparedness, which is crucial for regional security and global health resilience, especially in the MENA. It also highlights the significant role of AI analysis methods in enriching analytical outcomes in disaster medicine research and promoting data-informed preparedness strategies.
Asymptotic homogenisation is considered for problems with integral constraints imposed on a slowly varying microstructure; an insulator with an array of perfectly dielectric inclusions of slowly varying size serves as a paradigm. Although it is well-known how to handle each of these effects (integral constraints, slowly varying microstructure) independently within multiple scales analysis, additional care is needed when they are combined. Using the flux transport theorem, the multiple scales form of an integral constraint on a slowly varying domain is identified. The proposed form is applied to obtain a homogenised model for the electric potential in a dielectric composite, where the microstructure slowly varies and the integral constraint arises due to a statement of charge conservation. A comparison with multiple scales analysis of the problem with established approaches provides validation that the proposed form results in the correct homogenised model.
Bioreactor scaffolds must be designed to facilitate adequate nutrient delivery to the growing tissue they support. For perfusion bioreactors, the dominant transport process is determined by the scale of fluid velocity relative to diffusion and the geometry of the scaffold. In this paper, models of nutrient transport in a fibrous bioreactor scaffold are developed using homogenisation via multiscale asymptotics. The scaffold is modelled as an ensemble of aligned strings surrounded by viscous, slowly flowing fluid. Multiple scales analysis is carried out for various parameter regimes which give rise to macroscale transport models that incorporate the effects of advection, reaction and diffusion. Multiple scales in both space and time are employed when macroscale advection balances macroscale diffusion. The microscale model is solved to obtain the effective diffusion coefficient and simple solutions to the macroscale problem are presented for each regime.
Surfactant transport is central to a diverse range of natural phenomena with numerous practical applications in physics and engineering. Surprisingly, this process remains relatively poorly understood at the molecular scale. Here, we use non-equilibrium molecular dynamics (NEMD) simulations to study the spreading of sodium dodecyl sulphate on a thin film of liquid water. The molecular form of the control volume is extended to a coordinate system moving with the liquid–vapour interface to track surfactant spreading. We use this to compare the NEMD results to the continuum description of surfactant transport on an interface. By including the molecular details in the continuum model, we establish that the transport equation preserves substantial accuracy in capturing the underlying physics. Moreover, the relative importance of the different mechanisms involved in the transport process is identified. Consequently, we derive a novel exact molecular equation for surfactant transport along a deforming surface. Close agreement between the two conceptually different approaches, i.e. NEMD simulations and the numerical solution of the continuum equation, is found as measured by the surfactant concentration profiles, and the time dependence of the so-called spreading length. The current study focuses on a relatively simple specific solvent–surfactant system, and the observed agreement with the continuum model may not arise for more complicated industrially relevant surfactants and anti-foaming agents. In such cases, the continuum approach may fail to predict accompanying phase transitions, which can still be captured through the NEMD framework.
Objectives/Goals: We describe the prevalence of individuals with household exposure to SARS-CoV-2, who subsequently report symptoms consistent with COVID-19, while having PCR results persistently negative for SARS-CoV-2 (S[+]/P[-]). We assess whether paired serology can assist in identifying the true infection status of such individuals. Methods/Study Population: In a multicenter household transmission study, index patients with SARS-CoV-2 were identified and enrolled together with their household contacts within 1 week of index’s illness onset. For 10 consecutive days, enrolled individuals provided daily symptom diaries and nasal specimens for polymerase chain reaction (PCR). Contacts were categorized into 4 groups based on presence of symptoms (S[+/-]) and PCR positivity (P[+/-]). Acute and convalescent blood specimens from these individuals (30 days apart) were subjected to quantitative serologic analysis for SARS-CoV-2 anti-nucleocapsid, spike, and receptor-binding domain antibodies. The antibody change in S[+]/P[-] individuals was assessed by thresholds derived from receiver operating characteristic (ROC) analysis of S[+]/P[+] (infected) versusS[-]/P[-] (uninfected). Results/Anticipated Results: Among 1,433 contacts, 67% had ≥1 SARS-CoV-2 PCR[+] result, while 33% remained PCR[-]. Among the latter, 55% (n = 263) reported symptoms for at least 1 day, most commonly congestion (63%), fatigue (63%), headache (62%), cough (59%), and sore throat (50%). A history of both previous infection and vaccination was present in 37% of S[+]/P[-] individuals, 38% of S[-]/P[-], and 21% of S[+]/P[+] (P<0.05). Vaccination alone was present in 37%, 41%, and 52%, respectively. ROC analyses of paired serologic testing of S[+]/P[+] (n = 354) vs. S[-]/P[-] (n = 103) individuals found anti-nucleocapsid data had the highest area under the curve (0.87). Based on the 30-day antibody change, 6.9% of S[+]/P[-] individuals demonstrated an increased convalescent antibody signal, although a similar seroresponse in 7.8% of the S[-]/P[-] group was observed. Discussion/Significance of Impact: Reporting respiratory symptoms was common among household contacts with persistent PCR[-] results. Paired serology analyses found similar seroresponses between S[+]/P[-] and S[-]/P[-] individuals. The symptomatic-but-PCR-negative phenomenon, while frequent, is unlikely attributable to true SARS-CoV-2 infections that go missed by PCR.
Objectives/Goals: Accurately stratifying patients with clinically isolated syndrome by risk of developing multiple sclerosis is of great clinical importance. Though numerous prediction models attempt to achieve this goal, no systematic review exists to independently evaluate these models. We aim to systematically identify and assess the risk of bias in all such models. Methods/Study Population: Studies developing or validating prediction models to assess risk of developing MS in patients with CIS who are not receiving an MS-indicated disease-modifying therapeutic will be identified via a systematic literature search. Studies will be evaluated for overall risk of bias using PROBAST (Prediction model Risk Of Bias Assessment Tool). Briefly, data sources, predictor, and outcome definition and assessment, applicability, and analysis will be assessed for each model in each identified study, and an overall risk of biased judgment will be assigned. Identified studies, predictors incorporated, results, and risk of bias assessment with accompanying rationale will be summarized in the final report. Results/Anticipated Results: Based on an initial exploratory search, we anticipate that most, if not all, identified prediction models will have high risk of bias. We anticipate that many studies will have limited applicability due to the use of outdated diagnostic criteria for definition of outcomes, or high risk of bias concerns originating from their analysis due to insufficient volume of included participants or poor model validation practices. We further anticipate that most, if not all, of the identified prediction models will have limited potential to be translated to use in a clinical setting. Discussion/Significance of Impact: Understanding how to identify patients with high-risk CIS may inform and improve clinician treatment decisions, patient outcomes, and future research study design. This work may also reveal flaws in current prediction models for CIS, opening new avenues of research and prompting development of improved prognostic models for patients with CIS.
Objectives/Goals: This poster discusses key methodological and theoretical issues in translation and implementation for improving HPV vaccine recommendations in clinics serving rural communities. Methods/Study Population: Leveraging implementation science, the study of how to improve the uptake of evidence-based practices, this pilot study uses a mixed-methods effectiveness-implementation design to engage local experts in identifying a bundle of locally-tailored implementation strategies to facilitate uptake of evidence-based HPV vaccine recommendations. In partnership with the University of Arkansas for Medical Sciences Rural Research Network, we will follow an evidence-based quality improvement process to develop locally tailored implementation strategies, which we will then evaluate for acceptability, feasibility, and effectiveness. Results/Anticipated Results: This study aims to generate actionable insights into the design and implementation of tailored, evidence-based communication strategies that can be scaled to improve HPV vaccine uptake in rural communities. Findings from this pilot study will be used to support a future full-scale Hybrid-Type 3 effectiveness-implementation trial to evaluate the bundle of tailored implementation strategies. Discussion/Significance of Impact: By addressing the rural-specific determinants of evidence-based HPV vaccine recommendations, this research will contribute to a deeper understanding of how to support high-quality, evidence-based provider recommendations in rural, underserved communities, and will mitigate rural disparities in HPV-related cancers.