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Roman literature was by nature intertextual from the beginning, taking on the genres it inherited from the Greeks and adapting them within the constraints and zeities of native Roman prosody, Latin language, and Roman cultural differences. No longer seen under the sign of ‘influence’ or as part of the struggle to look or behave like the father – even when it is a matter of translation – this reality is rather seen as part of the dynamism of a literature that is as contentious, rivalrous and as preoccupied with dominating as the culture and state of which it was a part. Nor is the rivalry simply with the Greeks. Ennius takes an emulative and corrective stance with Naevius, updating his metre and much else. The prologues of Terence show that internal contention is as much a part of the game as any struggle to come to grips with and rearrange the sources in the poets of New Comedy.
Pharmacogenomic testing has emerged to aid medication selection for patients with major depressive disorder (MDD) by identifying potential gene-drug interactions (GDI). Many pharmacogenomic tests are available with varying levels of supporting evidence, including direct-to-consumer and physician-ordered tests. We retrospectively evaluated the safety of using a physician-ordered combinatorial pharmacogenomic test (GeneSight) to guide medication selection for patients with MDD in a large, randomized, controlled trial (GUIDED).
Materials and Methods
Patients diagnosed with MDD who had an inadequate response to ≥1 psychotropic medication were randomized to treatment as usual (TAU) or combinatorial pharmacogenomic test-guided care (guided-care). All received combinatorial pharmacogenomic testing and medications were categorized by predicted GDI (no, moderate, or significant GDI). Patients and raters were blinded to study arm, and physicians were blinded to test results for patients in TAU, through week 8. Measures included adverse events (AEs, present/absent), worsening suicidal ideation (increase of ≥1 on the corresponding HAM-D17 question), or symptom worsening (HAM-D17 increase of ≥1). These measures were evaluated based on medication changes [add only, drop only, switch (add and drop), any, and none] and study arm, as well as baseline medication GDI.
Most patients had a medication change between baseline and week 8 (938/1,166; 80.5%), including 269 (23.1%) who added only, 80 (6.9%) who dropped only, and 589 (50.5%) who switched medications. In the full cohort, changing medications resulted in an increased relative risk (RR) of experiencing AEs at both week 4 and 8 [RR 2.00 (95% CI 1.41–2.83) and RR 2.25 (95% CI 1.39–3.65), respectively]. This was true regardless of arm, with no significant difference observed between guided-care and TAU, though the RRs for guided-care were lower than for TAU. Medication change was not associated with increased suicidal ideation or symptom worsening, regardless of study arm or type of medication change. Special attention was focused on patients who entered the study taking medications identified by pharmacogenomic testing as likely having significant GDI; those who were only taking medications subject to no or moderate GDI at week 8 were significantly less likely to experience AEs than those who were still taking at least one medication subject to significant GDI (RR 0.39, 95% CI 0.15–0.99, p=0.048). No other significant differences in risk were observed at week 8.
These data indicate that patient safety in the combinatorial pharmacogenomic test-guided care arm was no worse than TAU in the GUIDED trial. Moreover, combinatorial pharmacogenomic-guided medication selection may reduce some safety concerns. Collectively, these data demonstrate that combinatorial pharmacogenomic testing can be adopted safely into clinical practice without risking symptom degradation among patients.
A cumulative environmental exposure score for schizophrenia (exposome score for schizophrenia [ES-SCZ]) may provide potential utility for risk stratification and outcome prediction. Here, we investigated whether ES-SCZ was associated with functioning in patients with schizophrenia spectrum disorder, unaffected siblings, and healthy controls.
This cross-sectional sample consisted of 1,261 patients, 1,282 unaffected siblings, and 1,525 healthy controls. The Global Assessment of Functioning (GAF) scale was used to assess functioning. ES-SCZ was calculated based on our previously validated method. The association between ES-SCZ and the GAF dimensions (symptom and disability) was analyzed by applying regression models in each group (patients, siblings, and controls). Additional models included polygenic risk score for schizophrenia (PRS-SCZ) as a covariate.
ES-SCZ was associated with the GAF dimensions in patients (symptom: B = −1.53, p-value = 0.001; disability: B = −1.44, p-value = 0.001), siblings (symptom: B = −3.07, p-value < 0.001; disability: B = −2.52, p-value < 0.001), and healthy controls (symptom: B = −1.50, p-value < 0.001; disability: B = −1.31, p-value < 0.001). The results remained the same after adjusting for PRS-SCZ. The degree of associations of ES-SCZ with both symptom and disability dimensions were higher in unaffected siblings than in patients and controls. By analyzing an independent dataset (the Genetic Risk and Outcome of Psychosis study), we replicated the results observed in the patient group.
Our findings suggest that ES-SCZ shows promise for enhancing risk prediction and stratification in research practice. From a clinical perspective, ES-SCZ may aid in efforts of clinical characterization, operationalizing transdiagnostic clinical staging models, and personalizing clinical management.
In April 2018, Public Health England was notified of cases of Shigella sonnei who had eaten food from three different catering outlets in England. The outbreaks were initially investigated as separate events, but whole-genome sequencing (WGS) showed they were caused by the same strain. The investigation included analyses of epidemiological data, the food chain and microbiological examination of food samples. WGS was used to determine the phylogenetic relatedness and antimicrobial resistance profile of the outbreak strain. Ultimately, 33 cases were linked to this outbreak; the majority had eaten food from seven outlets specialising in Indian or Middle Eastern cuisine. Five outlets were linked to two or more cases, all of which used fresh coriander although a shared supplier was not identified. An investigation at one of the venues recorded that 86% of cases reported eating dishes with coriander as an ingredient or garnish. Four cases were admitted to hospital and one had evidence of treatment failure with ciprofloxacin. Phylogenetic analysis showed that the outbreak strain was part of a wider multidrug-resistant clade associated with travel to Pakistan. Poor hygiene practices during cultivation, distribution or preparation of fresh produce are likely contributing factors.
Citizens’ beliefs about uncertain events are fundamental variables in many areas of political science. While beliefs are often conceptualized in the form of distributions, obtaining reliable measures in terms of full probability densities is a difficult task. In this letter, we ask if there is an effective way of eliciting beliefs as distributions in the context of online surveys. Relying on experimental evidence, we evaluate the performance of five different elicitation methods designed to capture citizens’ uncertain expectations. Our results suggest that an elicitation method originally proposed by Manski (2009) performs well. It measures average citizens’ subjective belief distributions reliably and is easily implemented in the context of regular (online) surveys. We expect that a wider use of this method will lead to considerable improvements in the study of citizens’ expectations and beliefs.
United States certified organic and conventional dairy farms are compared on the basis of economic, financial, and technological measures using dairy data from the 2016 USDA Agricultural Resource Management Survey. A stochastic production frontier model using an input distance function framework is estimated for U.S. dairy farms to examine technical efficiency and returns to scale (RTS) of farms of both systems and by multiple size categories. Financial and economic measures such as net return on assets and input costs, as well as technological adoption measures are compared by system and size. For both systems, size is the major determinant of competitiveness based on selected measures of productivity and RTS.
The recipients of NIH’s Clinical and Translational Science Awards (CTSA) have worked for over a decade to build informatics infrastructure in support of clinical and translational research. This infrastructure has proved invaluable for supporting responses to the current COVID-19 pandemic through direct patient care, clinical decision support, training researchers and practitioners, as well as public health surveillance and clinical research to levels that could not have been accomplished without the years of ground-laying work by the CTSAs. In this paper, we provide a perspective on our COVID-19 work and present relevant results of a survey of CTSA sites to broaden our understanding of the key features of their informatics programs, the informatics-related challenges they have experienced under COVID-19, and some of the innovations and solutions they developed in response to the pandemic. Responses demonstrated increased reliance by healthcare providers and researchers on access to electronic health record (EHR) data, both for local needs and for sharing with other institutions and national consortia. The initial work of the CTSAs on data capture, standards, interchange, and sharing policies all contributed to solutions, best illustrated by the creation, in record time, of a national clinical data repository in the National COVID-19 Cohort Collaborative (N3C). The survey data support seven recommendations for areas of informatics and public health investment and further study to support clinical and translational research in the post-COVID-19 era.
The contribution of neonatal cyanosis, inherent to cyanotic congenital heart disease, to the magnitude of neurologic injury during deep hypothermic circulatory arrest has not been fully delineated. This study investigates the impact of cyanosis and deep hypothermic circulatory arrest on brain injury.
Neonatal piglets were randomised to placement of a pulmonary artery to left atrium shunt to create cyanosis or sham thoracotomy. At day 7, animals were randomised to undergo deep hypothermic circulatory arrest or sham. Arterial oxygen tension and haematocrit were obtained. Neurobehavioural performance was serially assessed. The animals were sacrificed on day 14. Brain tissue was assessed for neuronal necrosis using a 5-point histopathologic score.
Four experimental groups were analysed (sham, n = 10; sham + deep hypothermic circulatory arrest, n = 8; shunt, n = 9; shunt + deep hypothermic circulatory arrest, n = 7). Cyanotic piglets had significantly higher haematocrit and lower partial pressure of oxygen at day 14 than non-cyanotic piglets. There were no statistically significant differences in neurobehavioural scores at day 1. However, shunt + deep hypothermic circulatory arrest piglets had evidence of greater neuronal injury than sham animals (median (range): 2 (0–4) versus 0 (0–0), p = 0.02).
Cyanotic piglets undergoing deep hypothermic circulatory arrest had increased neuronal injury compared to sham animals. Significant injury was not seen for either cyanosis or deep hypothermic circulatory arrest alone relative to shams. These findings suggest an interaction between cyanosis and deep hypothermic circulatory arrest and may partially explain the suboptimal neurologic outcomes seen in children with cyanotic heart disease who undergo deep hypothermic circulatory arrest.
In this paper, we consider the changing nature of today's protest–election connection by looking back to the Blue Wave of the 2018 midterm elections that led to Republicans losing control of the House of Representatives. We ask whether White voters' participation in the Blue Wave of the 2018 elections is related to the multi-racial participation in the #BlackLivesMatter protests of 2020. Could it be that White participation in both is symptomatic of a larger resurgence of racial liberalism that is likely to continue to play a significant role in our politics going forward starting with the 2020 election?
In premodern economic systems where the social embedding of exchange provided actors with the ability to control or monopolize trade, including the goods that enter and leave a marketplace, “restricted markets” formed. These markets produced external revenues that could be used to achieve political goals. Conversely, commercialized systems required investment in public goods that incentivize the development of market cooperation and “open markets,” where buyers and sellers from across social sectors and diverse communities could engage in exchange as economic equals within marketplaces. In this article, we compare market development at the Late Postclassic sites of Chetumal, Belize, and Tlaxcallan, Mexico. We identified a restricted market at Chetumal, using the distribution of exotic goods, particularly militarily and ritually charged obsidian projectile points; in contrast, an open market was built at Tlaxcallan. Collective action theory provides a useful framework to understand these differences in market development. We argue that Tlaxcaltecan political architects adopted more collective strategies, in which open markets figured, to encourage cooperation among an ethnically diverse population.
There is evidence that environmental and genetic risk factors for schizophrenia spectrum disorders are transdiagnostic and mediated in part through a generic pathway of affective dysregulation.
We analysed to what degree the impact of schizophrenia polygenic risk (PRS-SZ) and childhood adversity (CA) on psychosis outcomes was contingent on co-presence of affective dysregulation, defined as significant depressive symptoms, in (i) NEMESIS-2 (n = 6646), a representative general population sample, interviewed four times over nine years and (ii) EUGEI (n = 4068) a sample of patients with schizophrenia spectrum disorder, the siblings of these patients and controls.
The impact of PRS-SZ on psychosis showed significant dependence on co-presence of affective dysregulation in NEMESIS-2 [relative excess risk due to interaction (RERI): 1.01, p = 0.037] and in EUGEI (RERI = 3.39, p = 0.048). This was particularly evident for delusional ideation (NEMESIS-2: RERI = 1.74, p = 0.003; EUGEI: RERI = 4.16, p = 0.019) and not for hallucinatory experiences (NEMESIS-2: RERI = 0.65, p = 0.284; EUGEI: −0.37, p = 0.547). A similar and stronger pattern of results was evident for CA (RERI delusions and hallucinations: NEMESIS-2: 3.02, p < 0.001; EUGEI: 6.44, p < 0.001; RERI delusional ideation: NEMESIS-2: 3.79, p < 0.001; EUGEI: 5.43, p = 0.001; RERI hallucinatory experiences: NEMESIS-2: 2.46, p < 0.001; EUGEI: 0.54, p = 0.465).
The results, and internal replication, suggest that the effects of known genetic and non-genetic risk factors for psychosis are mediated in part through an affective pathway, from which early states of delusional meaning may arise.
The seroprevalence of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) IgG antibody was evaluated among employees of a Veterans Affairs healthcare system to assess potential risk factors for transmission and infection.
All employees were invited to participate in a questionnaire and serological survey to detect antibodies to SARS-CoV-2 as part of a facility-wide quality improvement and infection prevention initiative regardless of clinical or nonclinical duties. The initiative was conducted from June 8 to July 8, 2020.
Of the 2,900 employees, 51% participated in the study, revealing a positive SARS-CoV-2 seroprevalence of 4.9% (72 of 1,476; 95% CI, 3.8%–6.1%). There were no statistically significant differences in the presence of antibody based on gender, age, frontline worker status, job title, performance of aerosol-generating procedures, or exposure to known patients with coronavirus infectious disease 2019 (COVID-19) within the hospital. Employees who reported exposure to a known COVID-19 case outside work had a significantly higher seroprevalence at 14.8% (23 of 155) compared to those who did not 3.7% (48 of 1,296; OR, 4.53; 95% CI, 2.67–7.68; P < .0001). Notably, 29% of seropositive employees reported no history of symptoms for SARS-CoV-2 infection.
The seroprevalence of SARS-CoV-2 among employees was not significantly different among those who provided direct patient care and those who did not, suggesting that facility-wide infection control measures were effective. Employees who reported direct personal contact with COVID-19–positive persons outside work were more likely to have SARS-CoV-2 antibodies. Employee exposure to SARS-CoV-2 outside work may introduce infection into hospitals.
Within the Biostatistics, Epidemiology, and Research Design (BERD) component of the Northwestern University Clinical and Translational Sciences Institute, we created a mentoring program to complement training provided by the associated Multidisciplinary Career Development Program (KL2). Called Research design Analysis Methods Program (RAMP) Mentors, the program provides each KL2 scholar with individualized, hands-on mentoring in biostatistics, epidemiology, informatics, and related fields, with the goal of building multidisciplinary research teams. From 2015 to 2019, RAMP Mentors paired 8 KL2 scholars with 16 individually selected mentors. Mentors had funded/protected time to meet at least monthly with their scholar to provide advice and instruction on methods for ongoing research, including incorporating novel techniques. RAMP Mentors has been evaluated through focus groups and surveys. KL2 scholars reported high satisfaction with RAMP Mentors and confidence in their ability to establish and maintain methodologic collaborations. Compared with other Northwestern University K awardees, KL2 scholars reported higher confidence in obtaining research funding, including subsequent K or R awards, and selecting appropriate, up-to-date research methods. RAMP Mentors is a promising partnership between a BERD group and KL2 program, promoting methodologic education and building multidisciplinary research teams for junior investigators pursuing clinical and translational research.
The mitigation of CMAS (calcium–magnesium–aluminum–silicon oxide) infiltration is a major requirement for the stability of thermal barrier coatings. In this study, yttria-stabilized zirconia (YSZ)–Al2O3–SiC, YSZ–Al2O3–Ta2O5, and YSZ–Al2O3–Nb2O5 self-healing composites produced by uniaxially pressing powders were investigated as an alternative to YSZ. CMAS infiltration in these materials was tested at 1250 °C for 10 h. Comparing the depth of CMAS infiltration using scanning electron microscope (SEM) in tandem with electron-dispersive X-ray spectroscopy (EDS), all self-healing materials were found to perform better than the reference materials. While standard YSZ shows massive CMAS infiltration, SEM micrographs and EDS maps revealed a 33-fold improvement in CMAS resistance for the YSZ–Al2O3–Nb2O5 system, which exhibited the best performance among the selected self-repairing materials. X-ray diffraction and high-resolution SEM micrographs taken 10 μm below the surface revealed that CMAS only infiltrated pores in the topmost region of the samples. Both YSZ–Al2O3–Ta2O5 and YSZ–Al2O3–Nb2O5 systems showed no signs of chemical reaction with CMAS.
During the past decade, genetics research has allowed scientists and clinicians to explore the human genome in detail and reveal many thousands of common genetic variants associated with disease. Genetic risk scores, known as polygenic risk scores (PRSs), aggregate risk information from the most important genetic variants into a single score that describes an individual’s genetic predisposition to a given disease. This article reviews recent developments in the predictive utility of PRSs in relation to a person’s susceptibility to breast cancer and coronary artery disease. Prognostic models for these disorders are built using data from the UK Biobank, controlling for typical clinical and underwriting risk factors. Furthermore, we explore the possibility of adverse selection where genetic information about multifactorial disorders is available for insurance purchasers but not for underwriters. We demonstrate that prediction of multifactorial diseases, using PRSs, provides population risk information additional to that captured by normal underwriting risk factors. This research using the UK Biobank is in the public interest as it contributes to our understanding of predicting risk of disease in the population. Further research is imperative to understand how PRSs could cause adverse selection if consumers use this information to alter their insurance purchasing behaviour.
We describe 14 yr of public data from the Parkes Pulsar Timing Array (PPTA), an ongoing project that is producing precise measurements of pulse times of arrival from 26 millisecond pulsars using the 64-m Parkes radio telescope with a cadence of approximately 3 weeks in three observing bands. A comprehensive description of the pulsar observing systems employed at the telescope since 2004 is provided, including the calibration methodology and an analysis of the stability of system components. We attempt to provide full accounting of the reduction from the raw measured Stokes parameters to pulse times of arrival to aid third parties in reproducing our results. This conversion is encapsulated in a processing pipeline designed to track provenance. Our data products include pulse times of arrival for each of the pulsars along with an initial set of pulsar parameters and noise models. The calibrated pulse profiles and timing template profiles are also available. These data represent almost 21 000 h of recorded data spanning over 14 yr. After accounting for processes that induce time-correlated noise, 22 of the pulsars have weighted root-mean-square timing residuals of
in at least one radio band. The data should allow end users to quickly undertake their own gravitational wave analyses, for example, without having to understand the intricacies of pulsar polarisation calibration or attain a mastery of radio frequency interference mitigation as is required when analysing raw data files.
In 2015, excavations at Stainton Quarry, Furness, Cumbria, recovered remains that provide a unique insight into Early Neolithic farming in the vicinity. Five pits, a post-hole, and deposits within a tree-throw and three crevices in a limestone outcrop were investigated. The latter deposits yielded potentially the largest assemblage of Carinated Bowl fragments yet recovered in Cumbria. Lipid analysis identified dairy fats within nine of these sherds. This was consistent with previous larger studies but represents the first evidence that dairying was an important component of Early Neolithic subsistence strategies in Cumbria. In addition, two deliberately broken polished stone axes, an Arran pitchstone core, a small number of flint tools and debitage, and a tuff flake were retrieved. The site also produced moderate amounts of charred grain, hazelnut shell, charcoal, and burnt bone. Most of the charred grain came from an Early Neolithic pit and potentially comprises the largest assemblage of such material recovered from Cumbria to date. Radiocarbon dating indicated activity sometime during the 40th–35th centuries cal bc as well as an earlier presence during the 46th–45th centuries. Later activity during the Chalcolithic and the Early Bronze Age was also demonstrated. The dense concentration of material and the fragmentary and abraded nature of the pottery suggested redeposition from an above-ground midden. Furthermore, the data recovered during the investigation has wider implications regarding the nature and use of the surrounding landscape during the Early Neolithic and suggests higher levels of settlement permanence, greater reliance on domesticated resources, and a possible different topographical focus for settlement than currently proposed.
L’utilisation prolongée et les associations de benzodiazépines (BZD) anxiolytiques et hypnotiques exposent à des risques à court et long terme (dépendance, démence, troubles psychomoteurs…). Selon la Haute Autorité de santé (HAS), il n’y a pas lieu d’associer une BZD et un apparenté (zopiclone ou zolpidem) le soir.
– Évaluer les habitudes de prescription des BZD et de leurs apparentés hypnotiques dans une population de patients suivis en psychiatrie hospitalière.
– Suivre sur 6 années l’évolution de ces pratiques de prescription et l’émergence d’alternatives thérapeutiques aux BZD.
– Établir un parallèle avec les recommandations et les actualités de la littérature au sujet de ces risques pendant cette même période.
L’étude rétrospective a été réalisée au centre hospitalier Henri-Laborit (Poitiers) en sélectionnant les ordonnances informatisées comportant des BZD et/ou apparentés sur une période allant du 1er janvier 2008 au 31 décembre 2013, par tranche d’une année. Les associations de ces molécules et leurs posologies ont été répertoriées.
L’analyse de 6511 ordonnances a notamment mis en évidence que la prescription de zolpidem ou zopiclone seuls, sans association à une benzodiazépine, est majoritaire (77,5 % des ordonnances en moyenne) jusqu’en 2010. Puis elle diminue fortement (plus que 38 % en 2013) et elle est inférieure à celle de benzodiazépine seule pendant les 3 années suivantes. Parallèlement, le nombre total d’ordonnances dans cet hôpital est en constante augmentation. L’association de benzodiazépine et d’apparentés sur une même ordonnance reste peu courante, dans 2 % des prescriptions en moyenne, mais la prise des deux se situe le soir dans 91 % des cas (69–100 %).
L’étude montre une diminution de prescription d’hypnotiques apparentés aux BZD, allant de pair avec les mises en garde sur leurs effets indésirables et aux actions de l’HAS. Leur association en soirée à des BZD reste présente et une étude prospective auprès des prescripteurs pour connaître leur choix d’alternative thérapeutique est nécessaire.