Archias the good immigrant

Cicero's Pro Archia has historically been taken as a bona fide expression of humanism. In this article, I demonstrate how this reading of the Pro Archia has allowed the political and cultural tensions in the speech to remain hidden. Cicero's vision of Archias as an idealized amalgam sanitizes both the poetic and the cultural identity of his Syrian client in favour of a projection which combined generic “Greekness” with a politicized invocation of the Roman poet, Q. Ennius. Contextualizing the Pro Archia within its contemporary political moment reveals that Cicero is consciously constructing a narrative of Archias as a “good immigrant.”Published versio

Improvement in thermoregulation outcomes following the implementation of a thermoregulation bundle for preterm infants

Aim: Hypothermia is associated with increased morbidity and mortality in preterm infants. A local audit revealed 60% preterm infants ≤32 weeks gestation and/or very low birth weight (VLBW) infants (<1500 g) had an abnormal body temperature at admission. This study compares thermoregulatory outcomes before and after the implementation of a thermoregulation bundle in the birthing environment. Methods: This retrospective cohort study reviewed thermoregulatory data for all inborn preterm (≤32 weeks) and/or VLBW infants for a period of 30 months before (Group 1: 1st January 2013 to 30 June 2015) and after changes to thermoregulation practice (Group 2: 1st July 2015 to 31 December 2017). The key practice changes included: improved anticipation and staff preparedness, wrapping infant in a polyethylene sheet, using a polyethylene lined bonnet, using servo-control mode at birth and during transport. Results: There were 282 and 286 infants in group 1 and group 2 respectively, with similar baseline characteristics. A clinically and statistically significant improvement was observed in the proportion of infants with normothermia (33% in group 1 to 60% in group 2, P < 0.0001) including the sub-group of extremely preterm (<28 weeks gestation) infants (38 to 60%, P = 0.0083). A higher mean admission temperature was observed for group 2 (36.10°C ± 0.78 in group 1 vs 36.52°C ± 0.61 in group 2, P < 0.0001). Moderate hypothermia was reduced by two-thirds in group 2 (41–12%, P = <0.0001). Conclusions: The introduction of a thermoregulation bundle improved admission temperature, improved the proportion of normothermia and reduced moderate hypothermia in preterm infants

Final report on project SP1210: Lowland peatland systems in England and Wales – evaluating greenhouse gas fluxes and carbon balances

Lowland peatlands represent one of the most carbon-rich ecosystems in the UK. As a result of widespread habitat modification and drainage to support agriculture and peat extraction, they have been converted from natural carbon sinks into major carbon sources, and are now amongst the largest sources of greenhouse gas (GHG) emissions from the UK land-use sector. Despite this, they have previously received relatively little policy attention, and measures to reduce GHG emissions either through re-wetting and restoration or improved management of agricultural land remain at a relatively early stage. In part, this has stemmed from a lack of reliable measurements on the carbon and GHG balance of UK lowland peatlands. This project aimed to address this evidence gap via an unprecedented programme of consistent, multi year field measurements at a total of 15 lowland peatland sites in England and Wales, ranging from conservation managed ‘near-natural’ ecosystems to intensively managed agricultural and extraction sites. The use of standardised measurement and data analysis protocols allowed the magnitude of GHG emissions and removals by peatlands to be quantified across this heterogeneous data set, and for controlling factors to be identified. The network of seven flux towers established during the project is believed to be unique on peatlands globally, and has provided new insights into the processes the control GHG fluxes in lowland peatlands. The work undertaken is intended to support the future development and implementation of agricultural management and restoration measures aimed at reducing the contribution of these important ecosystems to UK GHG emissions

Fractional flow reserve vs. angiography in guiding management to optimize outcomes in non-ST-segment elevation myocardial infarction: the British Heart Foundation FAMOUS-NSTEMI randomized trial

Aim: We assessed the management and outcomes of non-ST segment elevation myocardial infarction (NSTEMI) patients randomly assigned to fractional flow reserve (FFR)-guided management or angiography-guided standard care. Methods and results: We conducted a prospective, multicentre, parallel group, 1 : 1 randomized, controlled trial in 350 NSTEMI patients with &#8805; coronary stenosis &#8805;30% of the lumen diameter assessed visually (threshold for FFR measurement) (NCT01764334). Enrolment took place in six UK hospitals from October 2011 to May 2013. Fractional flow reserve was disclosed to the operator in the FFR-guided group (n = 176). Fractional flow reserve was measured but not disclosed in the angiography-guided group (n = 174). Fractional flow reserve &#8804;0.80 was an indication for revascularization by percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG). The median (IQR) time from the index episode of myocardial ischaemia to angiography was 3 (2, 5) days. For the primary outcome, the proportion of patients treated initially by medical therapy was higher in the FFR-guided group than in the angiography-guided group [40 (22.7%) vs. 23 (13.2%), difference 95% (95% CI: 1.4%, 17.7%), P = 0.022]. Fractional flow reserve disclosure resulted in a change in treatment between medical therapy, PCI or CABG in 38 (21.6%) patients. At 12 months, revascularization remained lower in the FFR-guided group [79.0 vs. 86.8%, difference 7.8% (−0.2%, 15.8%), P = 0.054]. There were no statistically significant differences in health outcomes and quality of life between the groups. Conclusion: In NSTEMI patients, angiography-guided management was associated with higher rates of coronary revascularization compared with FFR-guided management. A larger trial is necessary to assess health outcomes and cost-effectiveness

Multi-ancestry Mendelian randomization of omics traits revealing drug targets of COVID-19 severity

BACKGROUND: Recent omic studies prioritised several drug targets associated with coronavirus disease 2019 (COVID-19) severity. However, little evidence was provided to systematically estimate the effect of drug targets on COVID-19 severity in multiple ancestries. METHODS: In this study, we applied Mendelian randomization (MR) and colocalization approaches to understand the putative causal effects of 16,059 transcripts and 1608 proteins on COVID-19 severity in European and effects of 610 proteins on COVID-19 severity in African ancestry. We further integrated genetics, clinical and literature evidence to prioritise drug targets. Additional sensitivity analyses including multi-trait colocalization and phenome-wide MR were conducted to test for MR assumptions. FINDINGS: MR and colocalization prioritized four protein targets, FCRL3, ICAM5, ENTPD5 and OAS1 that showed effect on COVID-19 severity in European ancestry. One protein target, SERPINA1 showed a stronger effect in African ancestry but much weaker effect in European ancestry (odds ratio [OR] in Africans=0.369, 95%CI=0.203 to 0.668, P = 9.96 × 10(−4); OR in Europeans=1.021, 95%CI=0.901 to 1.157, P = 0.745), which suggested that increased level of SERPINA1 will reduce COVID-19 risk in African ancestry. One protein, ICAM1 showed suggestive effect on COVID-19 severity in both ancestries (OR in Europeans=1.152, 95%CI=1.063 to 1.249, P = 5.94 × 10(−4); OR in Africans=1.481, 95%CI=1.008 to 2.176; P = 0.045). The OAS1, SERPINA1 and ICAM1 effects were replicated using updated COVID-19 severity data in the two ancestries respectively, where alternative splicing events in OAS1 and ICAM1 also showed marginal effects on COVID-19 severity in Europeans. The phenome-wide MR of the prioritised targets on 622 complex traits provided information on potential beneficial effects on other diseases and suggested little evidence of adverse effects on major complications. INTERPRETATION: Our study identified six proteins as showing putative causal effects on COVID-19 severity. OAS1 and SERPINA1 were targets of existing drugs in trials as potential COVID-19 treatments. ICAM1, ICAM5 and FCRL3 are related to the immune system. Across the six targets, OAS1 has no reliable instrument in African ancestry; SERPINA1, FCRL3, ICAM5 and ENTPD5 showed a different level of putative causal evidence in European and African ancestries, which highlights the importance of more powerful ancestry-specific GWAS and value of multi-ancestry MR in informing the effects of drug targets on COVID-19 across different populations. This study provides a first step towards clinical investigation of beneficial and adverse effects of COVID-19 drug targets. FUNDING: No

Ecrg4 expression and its product augurin in the choroid plexus: impact on fetal brain development, cerebrospinal fluid homeostasis and neuroprogenitor cell response to CNS injury

<p>Abstract</p> <p>Background</p> <p>The content and composition of cerebrospinal fluid (CSF) is determined in large part by the choroid plexus (CP) and specifically, a specialized epithelial cell (CPe) layer that responds to, synthesizes, and transports peptide hormones into and out of CSF. Together with ventricular ependymal cells, these CPe relay homeostatic signals throughout the central nervous system (CNS) and regulate CSF hydrodynamics. One new candidate signal is augurin, a newly recognized 14 kDa protein that is encoded by <it>esophageal cancer related gene-4 </it>(<it>Ecrg4</it>), a putative tumor suppressor gene whose presence and function in normal tissues remains unexplored and enigmatic. The aim of this study was to explore whether <it>Ecrg4 </it>and its product augurin, can be implicated in CNS development and the response to CNS injury.</p> <p>Methods</p> <p><it>Ecrg4 </it>gene expression in CNS and peripheral tissues was studied by <it>in situ </it>hybridization and quantitative RT-PCR. Augurin, the protein encoded by <it>Ecrg4</it>, was detected by immunoblotting, immunohistochemistry and ELISA. The biological consequence of augurin over-expression was studied in a cortical stab model of rat CNS injury by intra-cerebro-ventricular injection of an adenovirus vector containing the <it>Ecrg4 </it>cDNA. The biological consequences of reduced augurin expression were evaluated by characterizing the CNS phenotype caused by <it>Ecrg4 </it>gene knockdown in developing zebrafish embryos.</p> <p>Results</p> <p>Gene expression and immunohistochemical analyses revealed that, the CP is a major source of <it>Ecrg4 </it>in the CNS and that <it>Ecrg4 </it>mRNA is predominantly localized to choroid plexus epithelial (CPe), ventricular and central canal cells of the spinal cord. After a stab injury into the brain however, both augurin staining and <it>Ecrg4 </it>gene expression decreased precipitously. If the loss of augurin was circumvented by over-expressing <it>Ecrg4 in vivo</it>, BrdU incorporation by cells in the subependymal zone decreased. Inversely, gene knockdown of <it>Ecrg4 </it>in developing zebrafish embryos caused increased proliferation of GFAP-positive cells and induced a dose-dependent hydrocephalus-like phenotype that could be rescued by co-injection of antisense morpholinos with <it>Ecrg4 </it>mRNA.</p> <p>Conclusion</p> <p>An unusually elevated expression of the <it>Ecrg4 </it>gene in the CP implies that its product, augurin, plays a role in CP-CSF-CNS function. The results are all consistent with a model whereby an injury-induced decrease in augurin dysinhibits target cells at the ependymal-subependymal interface. We speculate that the ability of CP and ependymal epithelium to alter the progenitor cell response to CNS injury may be mediated, in part by <it>Ecrg4</it>. If so, the canonic control of its promoter by DNA methylation may implicate epigenetic mechanisms in neuroprogenitor fate and function in the CNS.</p

Mobility and kinship in the world’s first village societies

Around 10,000 y ago in southwest Asia, the cessation of a mobile lifestyle and the emergence of the first village communities during the Neolithic marked a fundamental change in human history. The first communities were small (tens to hundreds of individuals) but remained semisedentary. So-called megasites appeared soon after, occupied by thousands of more sedentary inhabitants. Accompanying this shift, the material culture and ancient ecological data indicate profound changes in economic and social behavior. A shift from residential to logistical mobility and increasing population size are clear and can be explained by either changes in fertility and/or aggregation of local groups. However, as sedentism increased, small early communities likely risked inbreeding without maintaining or establishing exogamous relationships typical of hunter-gatherers. Megasites, where large populations would have made endogamy sustainable, could have avoided this risk. To examine the role of kinship practices in the rise of megasites, we measured strontium and oxygen isotopes in tooth enamel from 99 individuals buried at Pınarbaşı, Boncuklu, and Çatalhöyük (Turkey) over 7,000 y. These sites are geographically proximate and, critically, span both early sedentary behaviors (Pınarbaşı and Boncuklu) and the rise of a local megasite (Çatalhöyük). Our data are consistent with the presence of only local individuals at Pınarbaşı and Boncuklu, whereas at Çatalhöyük, several nonlocals are present. The Çatalhöyük data stand in contrast to other megasites where bioarchaeological evidence has pointed to strict endogamy. These different kinship behaviors suggest that megasites may have arisen by employing unique, community-specific kinship practices

Mobility and kinship in the world's first village societies

Around 10,000 y ago in southwest Asia, the cessation of a mobile lifestyle and the emergence of the first village communities during the Neolithic marked a fundamental change in human history. The first communities were small (tens to hundreds of individuals) but remained semisedentary. So-called megasites appeared soon after, occupied by thousands of more sedentary inhabitants. Accompanying this shift, the material culture and ancient ecological data indicate profound changes in economic and social behavior. A shift from residential to logistical mobility and increasing population size are clear and can be explained by either changes in fertility and/or aggregation of local groups. However, as sedentism increased, small early communities likely risked inbreeding without maintaining or establishing exogamous relationships typical of hunter-gatherers. Megasites, where large populations would have made endogamy sustainable, could have avoided this risk. To examine the role of kinship practices in the rise of megasites, we measured strontium and oxygen isotopes in tooth enamel from 99 individuals buried at Pınarbaşı, Boncuklu, and Çatalhöyük (Turkey) over 7,000 y. These sites are geographically proximate and, critically, span both early sedentary behaviors (Pınarbaşı and Boncuklu) and the rise of a local megasite (Çatalhöyük). Our data are consistent with the presence of only local individuals at Pınarbaşı and Boncuklu, whereas at Çatalhöyük, several nonlocals are present. The Çatalhöyük data stand in contrast to other megasites where bioarchaeological evidence has pointed to strict endogamy. These different kinship behaviors suggest that megasites may have arisen by employing unique, community-specific kinship practices

Working with female offenders in restorative justice frameworks: Effective and ethical practice

Despite a recent increase in restorative justice practice in the criminal justice system, to date there has been no in-depth consideration of the impact of gender in these settings. This paper presents findings from a unique qualitative study on female offenders’ experiences of restorative conferencing in England and Wales, drawing on interviews with practitioners who have worked with female cases, as well as with women who have gone through a restorative justice conference in a perpetrator capacity. Gender specific factors, suggested to be especially valuable for practitioners to consider when delivering effective and ethical restorative conferences with female offenders, are outlined