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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.
This collection gathers thirteen contributions by a number of historians, friends, colleagues and/or students of Jinty’s, who were asked to pick their favourite article by her and say a few words about it for an event held in her memory on 15 January 2025 at King’s College London. We offer this collection in print now for a wider audience not so much because it has any claim to be exhaustive or authoritative, but because taken all together these pieces seemed to add up to a useful retrospective on Jinty’s work, its wider context, and its impact on the field over the decades. We hope that, for those who know her work well already, this may be an opportunity to remember some of her classic (and a few less classic) articles, while at the same time serving as an accessible introduction to her research for anyone who knew her without necessarily knowing about her field, as well as for a new and younger generation of readers.
Background: Artificial intelligence (AI) holds promise to predict outcomes for patients sustaining moderate to severe traumatic brain injury (msTBI). This systematic review sought to identify studies utilizing AI-based methods to predict mortality and functional outcomes after msTBI, where prognostic uncertainty is highest. Methods: The APPRAISE-AI quantitative evidence appraisal tool was used to evaluate methodological quality of included studies by determining overall scores and domain-specific scores. We constructed a multivariable linear regression model using study sample size, country of data collection, publication year and journal impact factor to quantify associations with overall APPRAISE-AI scores. Results: We identified 38 studies comprising 591,234 patients with msTBI. Median APPRAISE-AI score was 45.5 (/100 points), corresponding to moderate study quality. There were 13 low-quality studies (34%) and only 5 high-quality studies (13%). Weakest domains were methodological conduct, robustness of results and reproducibility. Multivariable linear regression highlighted that higher journal impact factor, larger sample size, more recent publication year and use of data that were collected in a high-income country were associated with higher APPRAISE-AI overall scores. Conclusions: We identified several study weaknesses of existing AI-based prediction models for msTBI; this work highlights methodological domains that require quality improvement to ultimately ensure safety and effiicacy of clinical AI models.
Background: Congenital myopathies (CM) are inherited muscle disorders historically classified according to features seen on muscle biopsy and congenital-onset weakness and hypotonia. The aim of our study was to evaluate the benefit of genetic testing, muscle biopsy, NCS/EMG and muscle MRI in obtaining a definite diagnosis for these patients. Methods: A retrospective chart review of all patients diagnosed at a single tertiary-care pediatric hospital over 15 years (2008-2022). REB approval was obtained. Results: Over a period of 15 years, 42 patients with CM were included. All (100%) had genetic testing (i.e. gene panel, WES), 65.9% had muscle biopsy, 67.5% had NCS/EMG and 20% had a muscle MRI. Definite diagnosis was obtained in 38% by genetic testing only, while 42.8% had a diagnosis made by genetic testing supported by the findings of one or more of the other diagnostic tools. Conclusions: Early diagnosis of CM is still essential in congenital myopathies to provide optimal care. Genetic testing is the gold standard for diagnosis, but other diagnostic tools remain valuable in the case of variants of unclear significance.
On February 6, 1968, leaders of the Southern Christian Leadership Conference drafted a letter addressed to the president, Congress, and the U.S. Supreme Court. The letter argued that the U.S. constitution facilitated economic and social second-class citizenship because the constitution did not protect economic and social rights but instead protected only civil and political rights. The letter’s authors demanded that the nation repent for its continued subordination of the poor and minorities and atone by recognizing economic and social rights. In this article, the authors recover the draft letter—a proposed economic and social bill of rights—and assert it was and remains a morally compelling call to recognize and protect positive fundamental rights under the constitution. The authors maintain that while the SCLC leaders who drafted the letter were clear that law alone could not end the sinful conditions that created racism and poverty, they were becoming more adamant that a radical redesign of the constitution was a necessary step toward building a beloved community.
We describe caudal analgesia agent, dose, reported adverse events, and outcomes in a single-centre, retrospective cohort study of 200 patients undergoing cardiac surgery from October 2020 to April 2023. Median (interquartile range) doses of clonidine and morphine were 2.7 (2.1–3) mCg/kg and 0.12 (0.1–1.12) mg/kg, respectively. Our findings suggest that a clonidine/morphine caudal was tolerated in cardiac surgical patients.
DSM-5 specifies bulimia nervosa (BN) severity based on specific thresholds of compensatory behavior frequency. There is limited empirical support for such severity groupings. Limited support could be because the DSM-5’s compensatory behavior frequency cutpoints are inaccurate or because compensatory behavior frequency does not capture true underlying differences in severity. In support of the latter possibility, some work has suggested shape/weight overvaluation or use of single versus multiple purging methods may be better severity indicators. We used structural equation modeling (SEM) Trees to empirically determine the ideal variables and cutpoints for differentiating BN severity, and compared the SEM Tree groupings to alternate severity classifiers: the DSM-5 indicators, single versus multiple purging methods, and a binary indicator of shape/weight overvaluation.
Methods
Treatment-seeking adolescents and adults with BN (N = 1017) completed self-report measures assessing BN and comorbid symptoms. SEM Trees specified an outcome model of BN severity and recursively partitioned this model into subgroups based on shape/weight overvaluation and compensatory behaviors. We then compared groups on clinical characteristics (eating disorder symptoms, depression, anxiety, and binge eating frequency).
Results
SEM Tree analyses resulted in five severity subgroups, all based on shape/weight overvaluation: overvaluation <1.25; overvaluation 1.25–3.74; overvaluation 3.75–4.74; overvaluation 4.75–5.74; and overvaluation ≥5.75. SEM Tree groups explained 1.63–6.41 times the variance explained by other severity schemes.
Conclusions
Shape/weight overvaluation outperformed the DSM-5 severity scheme and single versus multiple purging methods, suggesting the DSM-5 severity scheme should be reevaluated. Future research should examine the predictive utility of this severity scheme.
We undertake a comprehensive investigation into the distribution of in situ stars within Milky Way-like galaxies, leveraging TNG50 simulations and comparing their predictions with data from the H3 survey. Our analysis reveals that 28% of galaxies demonstrate reasonable agreement with H3, while only 12% exhibit excellent alignment in their profiles, regardless of the specific spatial cut employed to define in situ stars. To uncover the underlying factors contributing to deviations between TNG50 and H3 distributions, we scrutinise correlation coefficients among internal drivers (e.g. virial radius, star formation rate [SFR]) and merger-related parameters (such as the effective mass-ratio, mean distance, average redshift, total number of mergers, average spin-ratio, and maximum spin alignment between merging galaxies). Notably, we identify significant correlations between deviations from observational data and key parameters such as the median slope of virial radius, mean SFR values, and the rate of SFR change across different redshift scans. Furthermore, positive correlations emerge between deviations from observational data and parameters related to galaxy mergers. We validate these correlations using the Random Forest Regression method. Our findings underscore the invaluable insights provided by the H3 survey in unravelling the cosmic history of galaxies akin to the Milky Way, thereby advancing our understanding of galactic evolution and shedding light on the formation and evolution of Milky Way-like galaxies in cosmological simulations.
Posttraumatic stress disorder (PTSD) has been associated with advanced epigenetic age cross-sectionally, but the association between these variables over time is unclear. This study conducted meta-analyses to test whether new-onset PTSD diagnosis and changes in PTSD symptom severity over time were associated with changes in two metrics of epigenetic aging over two time points.
Methods
We conducted meta-analyses of the association between change in PTSD diagnosis and symptom severity and change in epigenetic age acceleration/deceleration (age-adjusted DNA methylation age residuals as per the Horvath and GrimAge metrics) using data from 7 military and civilian cohorts participating in the Psychiatric Genomics Consortium PTSD Epigenetics Workgroup (total N = 1,367).
Results
Meta-analysis revealed that the interaction between Time 1 (T1) Horvath age residuals and new-onset PTSD over time was significantly associated with Horvath age residuals at T2 (meta β = 0.16, meta p = 0.02, p-adj = 0.03). The interaction between T1 Horvath age residuals and changes in PTSD symptom severity over time was significantly related to Horvath age residuals at T2 (meta β = 0.24, meta p = 0.05). No associations were observed for GrimAge residuals.
Conclusions
Results indicated that individuals who developed new-onset PTSD or showed increased PTSD symptom severity over time evidenced greater epigenetic age acceleration at follow-up than would be expected based on baseline age acceleration. This suggests that PTSD may accelerate biological aging over time and highlights the need for intervention studies to determine if PTSD treatment has a beneficial effect on the aging methylome.
People with severe mental illness (SMI) have a higher risk of premature mortality than the general population.
Aims
To investigate whether the life expectancy gap for people with SMI is widening, by determining time trends in excess life-years lost.
Method
This population-based study included people with SMI (schizophrenia, bipolar disorder and major depression) alive on 1 January 2000. We ascertained SMI from psychiatric hospital admission records (1981–2019), and deaths via linkage to the national death register (2000–2019). We used the Life Years Lost (LYL) method to estimate LYL by SMI and sex, compared LYL to the Scottish population and assessed trends over 18 3-year rolling periods.
Results
We included 28 797 people with schizophrenia, 16 657 with bipolar disorder and 72 504 with major depression. Between 2000 and 2019, life expectancy increased in the Scottish population but the gap widened for people with schizophrenia. For 2000–2002, men and women with schizophrenia lost an excess 9.4 (95% CI 8.5–10.3) and 8.2 (95% CI 7.4–9.0) life-years, respectively, compared with the general population. In 2017–2019, this increased to 11.8 (95% CI 10.9–12.7) and 11.1 (95% CI 10.0–12.1). The life expectancy gap was lower for bipolar disorder and depression and unchanged over time.
Conclusions
The life expectancy gap in people with SMI persisted or widened from 2000 to 2019. Addressing this entrenched disparity requires equitable social, economic and health policies, healthcare re-structure and improved resourcing, and investment in interventions for primary and secondary prevention of SMI and associated comorbidities.
Glufosinate serves as both a primary herbicide option and a complement to glyphosate and other postemergence herbicides for managing herbicide-resistant weed species. Enhancing broadleaf weed control with glufosinate through effective mixtures may mitigate further herbicide resistance evolution in soybean and other glufosinate-resistant cropping systems. Two field experiments were conducted in 2020 and 2021 at four locations in Wisconsin (Arlington, Brooklyn, Janesville, and Lancaster) and one in Illinois (Macomb) to evaluate the effects of postemergence-applied glufosinate mixed with inhibitors of protoporphyrinogen oxidase (PPO) (flumiclorac-pentyl, fluthiacet-methyl, fomesafen, and lactofen; Group 14 herbicides), bentazon (a Group 6 herbicide), and 2,4-D (a Group 4 herbicide) on waterhemp control, soybean phytotoxicity, and yield. The experiments were established in a randomized, complete block design with four replications. The first experiment focused on soybean phytotoxicity 14 d after treatment (DAT) and yield in the absence of weed competition. All treatments received a preemergence herbicide, with postemergence herbicide applications occurring between the V3 and V6 soybean growth stages, depending on the site-year. The second experiment evaluated the effect of herbicide treatments on waterhemp control 14 DAT and on soybean yield. Lactofen, applied alone or with glufosinate, produced the greatest phytotoxicity to soybean at 14 DAT, but this injury did not translate into yield loss. Mixing glufosinate with 2,4-D, bentazon, and PPO-inhibitor herbicides did not increase waterhemp control, nor did it affect soybean yield compared to when glufosinate was applied alone, but it may be an effective practice to reduce selection pressure for glufosinate-resistant waterhemp.
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.
Corn (Zea mays L.) is an important crop that contributes to global food security, but understanding how farm management practices and soil health affect corn grain nutrient analysis and therefore human health is lacking. Leveraging Rodale Institute's Farming Systems Trial—a long-term field experiment established in 1981 in Kutztown, PA, USA—this study was conducted to assess the impact of different agricultural management systems on corn grain nutrient profiles in a long-term trial that has resulted in differences in soil health indicators between treatments as a result of long-term management. The main plot factor was two tillage practices (intensive and reduced) and the subplot factor was four cropping systems (non-diversified conventional [nCNV], diversified conventional [dCNV], legume-based organic [ORG-LEG], and manure-based organic [ORG-MNR]). Generally, the levels of amino acids, vitamins, and protein in corn grain were greatest in the ORG-MNR system, followed by the ORG-LEG and dCNV systems, and finally the nCNV system. It is important to consider that the observed difference between the organic and conventionally grown grain could be due to variations in corn hybrids that were used in those systems. However, nutrient composition of corn differed within cropping systems but between management practices (diversified crop rotation and cover cropping) which also contributed to differences in soil health indicators (soil compaction, soil protein, and organic C levels) that may also influence grain nutrient concentrations. With the exception of methionine, nutrient concentration in corn grain was not affected by different tillage regimes. These findings provide novel information on corn grain nutritional quality of organic and conventional cropping systems after long-term management and give insights into how system-specific components affect nutrient composition of corn grain.
Preliminary evidence suggests that a ketogenic diet may be effective for bipolar disorder.
Aims
To assess the impact of a ketogenic diet in bipolar disorder on clinical, metabolic and magnetic resonance spectroscopy outcomes.
Method
Euthymic individuals with bipolar disorder (N = 27) were recruited to a 6- to 8-week single-arm open pilot study of a modified ketogenic diet. Clinical, metabolic and MRS measures were assessed before and after the intervention.
Results
Of 27 recruited participants, 26 began and 20 completed the ketogenic diet. For participants completing the intervention, mean body weight fell by 4.2 kg (P < 0.001), mean body mass index fell by 1.5 kg/m2 (P < 0.001) and mean systolic blood pressure fell by 7.4 mmHg (P < 0.041). The euthymic participants had average baseline and follow-up assessments consistent with them being in the euthymic range with no statistically significant changes in Affective Lability Scale-18, Beck Depression Inventory and Young Mania Rating Scale. In participants providing reliable daily ecological momentary assessment data (n = 14), there was a positive correlation between daily ketone levels and self-rated mood (r = 0.21, P < 0.001) and energy (r = 0.19 P < 0.001), and an inverse correlation between ketone levels and both impulsivity (r = −0.30, P < 0.001) and anxiety (r = −0.19, P < 0.001). From the MRS measurements, brain glutamate plus glutamine concentration decreased by 11.6% in the anterior cingulate cortex (P = 0.025) and fell by 13.6% in the posterior cingulate cortex (P = <0.001).
Conclusions
These findings suggest that a ketogenic diet may be clinically useful in bipolar disorder, for both mental health and metabolic outcomes. Replication and randomised controlled trials are now warranted.
This article reflects on the phrase ‘early medieval’ as applied to European history between the end of Roman political rule in the West and some indeterminate point in the tenth or eleventh centuries. It is framed with reference to Michael Wallace-Hadrill’s 1974 lecture entitled ‘Early Medieval History’, which serves as a foil for a discussion of the evolving historiographical landscape from 1974 to 2024. The origins and the chronology of the term’s adoption into English usage are reviewed and, with an eye to discourses of modernity, the elements of middle-ness and early-ness are dissected. Points of comparison and contrast with the notion of ‘early modernity’ are noted, while an emphasis on the entanglement of middle-ness with European-ness leads into a discussion of whether the term has any applicability to extra-European history. The article concludes by highlighting the value of the weak relationship of ‘early medieval’ to modernity.
Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).
Aims
We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.
Method
Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.
Results
Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.
Conclusions
We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.
Hand, foot and mouth disease (HFMD) is a contagious communicable disease, with a high incidence in children aged under 10 years. It is a mainly self-limiting disease but can also cause serious neurological or cardiopulmonary complications in some cases, which can lead to death. Little is known about the burden of HMFD on primary care health care services in the UK. The aim of this work was to describe trends in general practitioner (GP) consultations for HFMD in England from January 2017 to December 2022 using a syndromic surveillance network of GPs. Daily GP consultations for HFMD in England were extracted from 1 January 2017 to 31 December 2022. Mean weekly consultation rates per 100,000 population and 95% confidence intervals (CI) were calculated. Consultation rates and rate ratios (RR) were calculated by age group and sex. During the study period, the mean weekly consultation rate for HFMD (per 100,000 registered GP patients) was 1.53 (range of 0.27 to 2.47). In England, children aged 1–4 years old accounted for the largest affected population followed by children <1 years old. We observed a seasonal pattern of HFMD incidence during the non-COVID years, with a seasonal peak of mean weekly rates between months of September and December. HFMD is typically diagnosed clinically rather than through laboratory sampling. Therefore, the ability to look at the daily HFMD consultation rates provides an excellent epidemiological overview on disease trends. The use of a novel GP-in-hours surveillance system allowed a unique epidemiological insight into the recent trends of general practitioner consultations for HFMD. We demonstrate a male predominance of cases, the impact of the non-pharmaceutical interventions during the COVID-19 pandemic, and a change in the week in which the peak number of cases happens post-pandemic.
The global population and status of Snowy Owls Bubo scandiacus are particularly challenging to assess because individuals are irruptive and nomadic, and the breeding range is restricted to the remote circumpolar Arctic tundra. The International Union for Conservation of Nature (IUCN) uplisted the Snowy Owl to “Vulnerable” in 2017 because the suggested population estimates appeared considerably lower than historical estimates, and it recommended actions to clarify the population size, structure, and trends. Here we present a broad review and status assessment, an effort led by the International Snowy Owl Working Group (ISOWG) and researchers from around the world, to estimate population trends and the current global status of the Snowy Owl. We use long-term breeding data, genetic studies, satellite-GPS tracking, and survival estimates to assess current population trends at several monitoring sites in the Arctic and we review the ecology and threats throughout the Snowy Owl range. An assessment of the available data suggests that current estimates of a worldwide population of 14,000–28,000 breeding adults are plausible. Our assessment of population trends at five long-term monitoring sites suggests that breeding populations of Snowy Owls in the Arctic have decreased by more than 30% over the past three generations and the species should continue to be categorised as Vulnerable under the IUCN Red List Criterion A2. We offer research recommendations to improve our understanding of Snowy Owl biology and future population assessments in a changing world.