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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.
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.
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.
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.
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.
While clozapine has risks, relative risk of fatality is overestimated. The UK pharmacovigilance programme is efficient, but comparisons with other drugs can mislead because of reporting variations. Clozapine actually lowers mortality, partly by reducing schizophrenia-related suicides, but preventable deaths still occur. Clozapine should be used earlier and more widely, but there should be better monitoring and better management of toxicity.
To investigate the symptoms of SARS-CoV-2 infection, their dynamics and their discriminatory power for the disease using longitudinally, prospectively collected information reported at the time of their occurrence. We have analysed data from a large phase 3 clinical UK COVID-19 vaccine trial. The alpha variant was the predominant strain. Participants were assessed for SARS-CoV-2 infection via nasal/throat PCR at recruitment, vaccination appointments, and when symptomatic. Statistical techniques were implemented to infer estimates representative of the UK population, accounting for multiple symptomatic episodes associated with one individual. An optimal diagnostic model for SARS-CoV-2 infection was derived. The 4-month prevalence of SARS-CoV-2 was 2.1%; increasing to 19.4% (16.0%–22.7%) in participants reporting loss of appetite and 31.9% (27.1%–36.8%) in those with anosmia/ageusia. The model identified anosmia and/or ageusia, fever, congestion, and cough to be significantly associated with SARS-CoV-2 infection. Symptoms’ dynamics were vastly different in the two groups; after a slow start peaking later and lasting longer in PCR+ participants, whilst exhibiting a consistent decline in PCR- participants, with, on average, fewer than 3 days of symptoms reported. Anosmia/ageusia peaked late in confirmed SARS-CoV-2 infection (day 12), indicating a low discrimination power for early disease diagnosis.
The U.S. Department of Agriculture–Agricultural Research Service (USDA-ARS) has been a leader in weed science research covering topics ranging from the development and use of integrated weed management (IWM) tactics to basic mechanistic studies, including biotic resistance of desirable plant communities and herbicide resistance. ARS weed scientists have worked in agricultural and natural ecosystems, including agronomic and horticultural crops, pastures, forests, wild lands, aquatic habitats, wetlands, and riparian areas. Through strong partnerships with academia, state agencies, private industry, and numerous federal programs, ARS weed scientists have made contributions to discoveries in the newest fields of robotics and genetics, as well as the traditional and fundamental subjects of weed–crop competition and physiology and integration of weed control tactics and practices. Weed science at ARS is often overshadowed by other research topics; thus, few are aware of the long history of ARS weed science and its important contributions. This review is the result of a symposium held at the Weed Science Society of America’s 62nd Annual Meeting in 2022 that included 10 separate presentations in a virtual Weed Science Webinar Series. The overarching themes of management tactics (IWM, biological control, and automation), basic mechanisms (competition, invasive plant genetics, and herbicide resistance), and ecosystem impacts (invasive plant spread, climate change, conservation, and restoration) represent core ARS weed science research that is dynamic and efficacious and has been a significant component of the agency’s national and international efforts. This review highlights current studies and future directions that exemplify the science and collaborative relationships both within and outside ARS. Given the constraints of weeds and invasive plants on all aspects of food, feed, and fiber systems, there is an acknowledged need to face new challenges, including agriculture and natural resources sustainability, economic resilience and reliability, and societal health and well-being.
We describe the scientific goals and survey design of the First Large Absorption Survey in H i (FLASH), a wide field survey for 21-cm line absorption in neutral atomic hydrogen (H i) at intermediate cosmological redshifts. FLASH will be carried out with the Australian Square Kilometre Array Pathfinder (ASKAP) radio telescope and is planned to cover the sky south of $\delta \approx +40\,\deg$ at frequencies between 711.5 and 999.5 MHz. At redshifts between $z = 0.4$ and $1.0$ (look-back times of 4 – 8 Gyr), the H i content of the Universe has been poorly explored due to the difficulty of carrying out radio surveys for faint 21-cm line emission and, at ultra-violet wavelengths, space-borne searches for Damped Lyman-$\alpha$ absorption in quasar spectra. The ASKAP wide field of view and large spectral bandwidth, in combination with a radio-quiet site, will enable a search for absorption lines in the radio spectra of bright continuum sources over 80% of the sky. This survey is expected to detect at least several hundred intervening 21-cm absorbers and will produce an H i-absorption-selected catalogue of galaxies rich in cool, star-forming gas, some of which may be concealed from optical surveys. Likewise, at least several hundred associated 21-cm absorbers are expected to be detected within the host galaxies of radio sources at $0.4 < z < 1.0$, providing valuable kinematical information for models of gas accretion and jet-driven feedback in radio-loud active galactic nuclei. FLASH will also detect OH 18-cm absorbers in diffuse molecular gas, megamaser OH emission, radio recombination lines, and stacked H i emission.
To determine the incidence of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection among healthcare personnel (HCP) and to assess occupational risks for SARS-CoV-2 infection.
Design:
Prospective cohort of healthcare personnel (HCP) followed for 6 months from May through December 2020.
Setting:
Large academic healthcare system including 4 hospitals and affiliated clinics in Atlanta, Georgia.
Participants:
HCP, including those with and without direct patient-care activities, working during the coronavirus disease 2019 (COVID-19) pandemic.
Methods:
Incident SARS-CoV-2 infections were determined through serologic testing for SARS-CoV-2 IgG at enrollment, at 3 months, and at 6 months. HCP completed monthly surveys regarding occupational activities. Multivariable logistic regression was used to identify occupational factors that increased the risk of SARS-CoV-2 infection.
Results:
Of the 304 evaluable HCP that were seronegative at enrollment, 26 (9%) seroconverted for SARS-CoV-2 IgG by 6 months. Overall, 219 participants (73%) self-identified as White race, 119 (40%) were nurses, and 121 (40%) worked on inpatient medical-surgical floors. In a multivariable analysis, HCP who identified as Black race were more likely to seroconvert than HCP who identified as White (odds ratio, 4.5; 95% confidence interval, 1.3–14.2). Increased risk for SARS-CoV-2 infection was not identified for any occupational activity, including spending >50% of a typical shift at a patient’s bedside, working in a COVID-19 unit, or performing or being present for aerosol-generating procedures (AGPs).
Conclusions:
In our study cohort of HCP working in an academic healthcare system, <10% had evidence of SARS-CoV-2 infection over 6 months. No specific occupational activities were identified as increasing risk for SARS-CoV-2 infection.
The mechanics underlying ice–skate friction remain uncertain despite over a century of study. In the 1930s, the theory of self-lubrication from frictional heat supplanted an earlier hypothesis that pressure melting governed skate friction. More recently, researchers have suggested that a layer of abraded wear particles or the presence of quasi-liquid molecular layers on the surface of ice could account for its slipperiness. Here, we assess the dominant hypotheses proposed to govern ice–skate friction and describe experiments conducted in an indoor skating rink aimed to provide observations to test these hypotheses. Our results indicate that the brittle failure of ice under rapid compression plays a strong role. Our observations did not confirm the presence of full-contact water films and are more consistent with the presence of lubricating ice-rich slurries at discontinuous high-pressure zones (HPZs). The presence of ice-rich slurries supporting skates through HPZs merges pressure-melting, abrasion and lubricating films as a unified hypothesis for why skates are so slippery across broad ranges of speeds, temperatures and normal loads. We suggest tribometer experiments to overcome the difficulties of investigating these processes during actual skating trials.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
Aims
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Method
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Results
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
Conclusions
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
A novel paediatric disease, multi-system inflammatory syndrome in children, has emerged during the 2019 coronavirus disease pandemic.
Objectives:
To describe the short-term evolution of cardiac complications and associated risk factors in patients with multi-system inflammatory syndrome in children.
Methods:
Retrospective single-centre study of confirmed multi-system inflammatory syndrome in children treated from 29 March, 2020 to 1 September, 2020. Cardiac complications during the acute phase were defined as decreased systolic function, coronary artery abnormalities, pericardial effusion, or mitral and/or tricuspid valve regurgitation. Patients with or without cardiac complications were compared with chi-square, Fisher’s exact, and Wilcoxon rank sum.
Results:
Thirty-nine children with median (interquartile range) age 7.8 (3.6–12.7) years were included. Nineteen (49%) patients developed cardiac complications including systolic dysfunction (33%), valvular regurgitation (31%), coronary artery abnormalities (18%), and pericardial effusion (5%). At the time of the most recent follow-up, at a median (interquartile range) of 49 (26–61) days, cardiac complications resolved in 16/19 (84%) patients. Two patients had persistent mild systolic dysfunction and one patient had persistent coronary artery abnormality. Children with cardiac complications were more likely to have higher N-terminal B-type natriuretic peptide (p = 0.01), higher white blood cell count (p = 0.01), higher neutrophil count (p = 0.02), severe lymphopenia (p = 0.05), use of milrinone (p = 0.03), and intensive care requirement (p = 0.04).
Conclusion:
Patients with multi-system inflammatory syndrome in children had a high rate of cardiac complications in the acute phase, with associated inflammatory markers. Although cardiac complications resolved in 84% of patients, further long-term studies are needed to assess if the cardiac abnormalities (transient or persistent) are associated with major cardiac events.
Among 353 healthcare personnel in a longitudinal cohort in 4 hospitals in Atlanta, Georgia (May–June 2020), 23 (6.5%) had severe acute respiratory coronavirus virus 2 (SARS-CoV-2) antibodies. Spending >50% of a typical shift at the bedside (OR, 3.4; 95% CI, 1.2–10.5) and black race (OR, 8.4; 95% CI, 2.7–27.4) were associated with SARS-CoV-2 seropositivity.
It is not clear to what extent associations between schizophrenia, cannabis use and cigarette use are due to a shared genetic etiology. We, therefore, examined whether schizophrenia genetic risk associates with longitudinal patterns of cigarette and cannabis use in adolescence and mediating pathways for any association to inform potential reduction strategies.
Methods
Associations between schizophrenia polygenic scores and longitudinal latent classes of cigarette and cannabis use from ages 14 to 19 years were investigated in up to 3925 individuals in the Avon Longitudinal Study of Parents and Children. Mediation models were estimated to assess the potential mediating effects of a range of cognitive, emotional, and behavioral phenotypes.
Results
The schizophrenia polygenic score, based on single nucleotide polymorphisms meeting a training-set p threshold of 0.05, was associated with late-onset cannabis use (OR = 1.23; 95% CI = 1.08,1.41), but not with cigarette or early-onset cannabis use classes. This association was not mediated through lower IQ, victimization, emotional difficulties, antisocial behavior, impulsivity, or poorer social relationships during childhood. Sensitivity analyses adjusting for genetic liability to cannabis or cigarette use, using polygenic scores excluding the CHRNA5-A3-B4 gene cluster, or basing scores on a 0.5 training-set p threshold, provided results consistent with our main analyses.
Conclusions
Our study provides evidence that genetic risk for schizophrenia is associated with patterns of cannabis use during adolescence. Investigation of pathways other than the cognitive, emotional, and behavioral phenotypes examined here is required to identify modifiable targets to reduce the public health burden of cannabis use in the population.