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Advanced imaging techniques are enhancing research capacity focussed on the developmental origins of adult health and disease (DOHaD) hypothesis, and consequently increasing awareness of future health risks across various subareas of DOHaD research themes. Understanding how these advanced imaging techniques in animal models and human population studies can be both additively and synergistically used alongside traditional techniques in DOHaD-focussed laboratories is therefore of great interest. Global experts in advanced imaging techniques congregated at the advanced imaging workshop at the 2019 DOHaD World Congress in Melbourne, Australia. This review summarizes the presentations of new imaging modalities and novel applications to DOHaD research and discussions had by DOHaD researchers that are currently utilizing advanced imaging techniques including MRI, hyperpolarized MRI, ultrasound, and synchrotron-based techniques to aid their DOHaD research focus.
There is a long history in Lucretian scholarship of finding conflict in the DRN between its philosophical content and its poetic form. Recent criticism has emphasized rather how the poem’s poetic form complements its Epicurean message. This chapter argues for important differences between literary and philosophical approaches to the poem, in particular with regard to its relationship with other texts, in order to identify some important differences in common modes of reading the poem. The chapter examines a ‘master-text’ model of reading, in which the DRN is related in strong fashion to another text on which it is dependent. The precise nature and identity of this ‘master-text’ can vary, according to the purpose or use to which the DRN is put. The approach of such ‘master-text’ readings is strikingly different from the dominant intertextual mode. In the examples of intertextual reading examined, the relationship to the other text is not one of subordination, but a tool used by the DRN to serve a particular function within the poem itself. The modes of reading explored in this chapter can lead to real differences in interpretation: e.g., on the end of the DRN, or on how uncompromising or sympathetic we should view certain parts of the poem. One important consequence is the need to acknowledge the differences in our reading practices and theoretical assumptions.
OBJECTIVES/GOALS: We have recently shown that mice exposed to six days of 60% caloric restriction acutely display reduced hypoglycemia-induced glucagon release following refeeding, and that this effect is concurrent with low leptin levels. The current study was conducted to ascertain if leptin treatment during caloric restriction would reverse this effect. METHODS/STUDY POPULATION: Three groups of mice were used, an ad libitum (Ad-lib) fed group and two caloric restriction (CR) groups, one of which received twice daily leptin injection (0.5-1μg/g; IP) and the other vehicle (saline) during their caloric restriction. CR mice were placed on 60% caloric restriction for 6 consecutive days. Ad lib mice were housed in an identical manner but fed ad libitum during this same period. Following 6 days of restriction, CR mice were given ad lib access to food for 16 h. After the 16 h period of refeeding, both CR and ad lib mice began a 6 h fast which was immediately followed by a hypoglycemic insulin tolerance test (ITT). ITTs consisted of a variable dose of insulin intended to achieve a blood glucose of ~45 mg/dL within 60 minutes, at which time blood was collected for glucagon and corticosterone assays. RESULTS/ANTICIPATED RESULTS: The mean blood glucose levels during the ITT at 45 and 60 minutes post injection across all three groups were 46.8 + 3.1 and 37.0 + 2.4, respectively. There were no significant differences in glucose levels between the three groups at these two time points. As expected, saline treated CR mice displayed significantly reduced serum glucagon levels in response to the ITT relative to Ad-lib mice (23.5 + 10.9 vs. 91.7 + 20.8 pg/mL, p = 0.009). In contrast, leptin-treated CR mice maintained their hypoglycemia-induced glucagon response to the ITT (78.0 + 16.8 pg/mL, p>0.99 vs. Ad-lib group). In addition, although corticosterone levels in saline treated CR mice were numerically lower than in Ad-lib mice, this difference was not statistically significance (3928 + 277 vs. 4571 + 178 pg/mL, p = 0.179). DISCUSSION/SIGNIFICANCE OF IMPACT: Diabetes patients on insulin therapy often develop impaired hypoglycemic counter-regulation which can lead to life-threatening hypoglycemic complications. Our results suggest that leptin may hold promise as a therapeutic intervention for the prevention of impaired hypoglycemic counter-regulation in persons with diabetes.
Our study objective was to describe the Canadian emergency medicine (EM) research community landscape prior to the initiation of a nationwide network.
A two-phase electronic survey was sent to 17 Canadian medical schools. The Phase 1 Environmental Scan was administered to department chairs/hospital EM chiefs, to identify EM physicians conducting clinical or educational research. The Phase 2 Survey was sent to the identified EM researchers to assess four themes: 1) geographic distribution, 2) training/career satisfaction, 3) time/financial compensation, and 4) research facilitators/barriers. Descriptive analyses were conducted, and results were stratified by Canadian regions.
A total of 92 EM researchers were identified in Phase 1; 67 (73%) responded to the Phase 2 Survey. Of those, 42 (63%) reported being clinical researchers, and 19 (45%) had a graduate degree. Three provinces encompassed most of the researchers (n = 35). Of the respondents, 61% had a research degree, 66% felt adequately trained for their research career, 73% had financial support, 83% had access to office spaces, 52% had no mentor during their first years of their career, 69% felt satisfied with their research career, and 82% suggested that they will still be conducting research in 5 years.
EM researchers reported being adequately trained, even though only a little over half had a graduate degree. Only two-thirds had financial support, and mentorship was lacking in one-third of the participants. Not all respondents had a form of infrastructure, but most felt optimistic about their careers. The Canadian EM research environment could be improved to ensure better research capacity.
Introduction: Prognostication is a significant challenge early in the post-cardiac arrest period. Common prognostic factors for neurological survival are unreliable (high false positive rates) until 72 hours post-cardiac arrest. It is not known whether there are a combination of factors that can be utilized earlier in the post-cardiac arrest period to accurately predict patient outcome. Our objective was to predict neurological outcome utilizing a novel combination of patient factors early in the post-cardiac arrest period. Methods: We conducted a retrospective cohort study using data from our local cardiac arrest registry. We included adult patients who obtained a return of spontaneous circulation (ROSC) after out-of-hospital cardiac arrest (OHCA). We excluded patients who did not survive for at least 24 hours post-ROSC and those who had a do not resuscitate (DNR) order within 2 hours of ROSC. We performed an ordinal regression analysis using the proportional odds model to predict neurological outcome (modified rankin score (mRS)). We included a good neurological outcome (mRS 0-2), poor neurological outcome (mRS 3-5), and dead (mRS 6) as an ordinal outcome. We included a number of patient demographics, intra- and post-cardiac arrest factors as covariates in our model. The predictive performance of our model was analyzed using receiver operating characteristic (ROC) curves for discrimination and Brier statistic for calibration. Results: We included 3448 patients in our analysis. We found that an initial shockable rhythm (odds ratio (OR) 4.1; 95% confidence interval (CI) 3.6, 5.4), the absence of pupillary reflexes (OR 3.5; 95% CI 2.4,4.8) and maximum motor score on the Glasgow Coma Scale (GCS) (OR 1.5; 95% CI 1.4,1.6) had the greatest association with improved neurologic outcome. Longer duration of resuscitation was associate with worse outcomes (OR 0.84, 95% CI 0.82,0.87). The overall performance of our model was excellent with an area under the ROC curve of 0.89 and a Brier statistic of 0.13. Conclusion: Our model predicted good neurological outcome with a high rate of accuracy, however external validation of the model is required. This model may be useful in providing initial risk stratification of patients in clinical practice and future research on post-cardiac arrest care.
Introduction: Despite recent advances in resuscitation, some patients remain in ventricular fibrillation (VF) after multiple defibrillation attempts during out-of-hospital cardiac arrest (OHCA). Vector change defibrillation (VC) and double sequential external defibrillation (DSED) have been proposed as alternate therapeutic strategies for OHCA patients with refractory VF. The primary objective was to determine the feasibility, safety and sample size required for a future cluster randomized controlled trial (RCT) with crossover comparing VC or DSED to standard defibrillation for patients experiencing refractory VF. Secondary objectives were to evaluate the intervention effect on VF termination and return of spontaneous circulation (ROSC). Methods: We conducted a pilot cluster RCT with crossover in four Canadian paramedic services and included all treated adult OHCA patients who presented in VF and received a minimum of three defibrillation attempts. In addition to standard cardiac arrest care, each EMS service was randomly assigned to provide continued standard defibrillation (control), VC or DSED. Services crossed over to an alternate defibrillation strategy after six months. Prior to the launch of the trial, 2,500 paramedics received in-person training for VC and DSED defibrillation using a combination of didactic, video and simulated scenarios. Results: Between March 2018 and September 2019, 152 patients were enrolled. Monthly enrollment varied from 1.4 to 6.1 cases per service. With respect to feasibility, 89.5% of cases received the defibrillation strategy they were randomly allocated to, and 93.1% of cases received a VC or DSED shock prior to the sixth defibrillation attempt. There were no reported cases of defibrillator malfunction, skin burns, difficulty with pad placement or concerns expressed by paramedics, patients, families, or ED staff about the trial. In the standard defibrillation group, 66.6% of cases resulted in VF termination, compared to 82.0% in VC and 76.3% of cases in the DSED group. ROSC was achieved in 25.0%, 39.3% and 40.0% of standard, VC and DSED groups, respectively. Conclusion: Findings from our pilot RCT suggest the DOSE VF protocol is feasible and safe. VF termination and ROSC were higher with VC and DSED compared to standard defibrillation. The results of this pilot trial will allow us to inform a multicenter cluster RCT with crossover to determine if alternate defibrillation strategies for refractory VF may impact patient-centered, clinical outcomes
This retrospective, case series audit assessed the clinical and health-economic impact of long-term treatment with quetiapine (‘Seroquel’), a new atypical antipsychotic, in patients with chronic schizophrenia.
The study design was of a case series format, comprising patients entered from one centre into the open-label extension of a multicentre 6-week efficacy study. Twenty-one patients (15 male, six female; mean age 39 years) were studied, of whom 17 (81%) had been rated as ‘partially responsive’ to previous antipsychotics. Data on hospitalisations and information on symptoms were collected retrospectively for the 12 months before quetiapine treatment was initiated and for the 12 months after.
Quetiapine was effective in reducing psychotic symptoms with mean BPRS scores reducing significantly, from 38 to 21 (P < 0.005). Motor function was also significantly improved with mean Simpson scale scores reducing from 15 to 12 (P < 0.005). Average inpatient days were reduced by 11% in year two (97 compared with 109 days) while the overall costs of treatment, including drug costs, fell by 5% (I£20,843 to I£19,827).
Four patients had been hospitalised for longer than 5 years before starting quetiapine; these chronically institutionalised patients remained in hospital, despite improved clinical outcomes (mean BPRS scores after treatment of 34, compared with 43 before), for the full 12 months of quetiapine treatment. Were the data from this audit to be re-analysed excluding these four patients then average inpatient days would have been reduced by 33% (45 to 30 days) and overall cost of treatment by 19% (I£8617 to I£7011).
This audit suggests that treatment with quetiapine over this 1-year period was associated with both clinical improvements and a decreased usage of inpatient services. The reduction in hospitalisation costs would appear to compensate for the increased cost of drug treatment. Significantly, potential savings appear to be greatest for those patients with a ‘revolving door’ pattern of repeated readmission.
Antidepressant use has risen x3-5 in Western countries since the early 1990s, outstripping changes in depression incidence or prevalence. This represents a major public health challenge.
Nationally-collected antidepressant data were used to assess the impact of "Doing Well", (DW) a novel depression care programme operating in Renfrewshire, Scotland. "Doing Well" implemented a model of “stepped collaborative care”, practitioner education and significant service redesign. Prescribing was compared for three groups: "DW" (76,000 population; clinical and educational intervention), "DW neighbours” (101,000 population; educational interventions only), and Scotland (no specific intervention).
A national rise in antidepressant prescriptions was stabilised for the "DW" group (graph). Antidepressant cost/item fell by 42% and 40% in both “DW” and “DW neighbours” groups but rose by 8% nationally.
Access to clinical interventions are required to reduce antidepressant prescriptions, but cost savings may be made with educational interventions alone.
A main objective of EPOS is to provide a valid multifactorial model for the prediction of psychosis. One major element of such a model should be the clinical state.
In a European multicentre study, persons fulfilling clinical criteria thought to indicate an increased risk for psychosis (PAR) were assessed amongst others with different psychopathological instruments covering the whole spectrum from basic symptoms to frank psychotic symptoms. Inclusion criteria comprised attenuated positive symptoms (APS), brief limited intermittent psychotic symptoms (BLIPS), cognitive basic symptoms (CogDis) and a combination of family risk and reduced functioning (S&T).
246 PAR were included into the study, mostly by APS or CogDis. Analysis of demographical data showed a high amount of functional impairment, resulting e.g. in low mean GAF scores (51.0 ± 11.8 SD), and of non-psychotic axis-I disorders. In September 2006, the hazard rate for a conversion to psychosis was 15.3 at 12 and 20.0 at 18 months after baseline assessment. According to the inclusion criteria, the highest rate of conversion was observed among PAR with BLIPS. On a dimensional level, a low GAF score was among the best predictors of conversion.
The transition rates of EPOS were in line with recent studies. A first analysis of clinical data supports the notion that the functional state should be an inherent part of any set of clinical risk criteria. Further analysis will consider the contribution of single symptoms or symptom combinations and the impact of symptom duration.
One aim of the European prediction of psychosis study (EPOS) has been to evaluate the clinical course of putatively prodromal patients in terms of psychopathology.
245 patients at risk for psychosis defined by attenuated positive symptoms, brief limited psychotic symptoms, a state/ trait combination or cognitive-perceptive basic symptoms was recruited in six centres in four countries. The Structured Interview for Prodromal Syndromes (SIPS) and the Bonn Scale for the Assessment of Basic Symptoms – Prediction List (BSABS-P) were employed. Follow-up was scheduled after 9 months (t1) and 18 months.
In total, 40 patients developed a psychosis (P). Compared to those without a transition (NP), P showed significantly higher SIPS scores at baseline. The same applied to the BSABS-P sub-scores 'cognitive perception disturbances' and 'cognitive motor disturbances'. The P sub-group developing psychosis after t1 showed no significant change of the SIPS positive (SIPS-P) sub-score or of any BSABS-P score from baseline to t1, whereas all scores improved in the NP group. At t1, SIPS-P and BSABS-P sub-score 'cognitive thought disturbances' were significantly lower in those later becoming psychotic.
Patients at risk showing a transition to psychosis during exhibited a pronounced psychopathology at baseline. Also, the positive symptom scores did not significantly improve during 1st follow-up, whereas those patients with no transition during the complete follow-up showed an improvement of all scores. As EPOS is a naturalistic study, different treatments have been performed in a considerable portion of the patients and association with course awaits further analysis.
In this chapter I focus attention on the ways in which the Argonautica combines different attitudes to the past and its connections with the present: once again, historiography (especially Herodotean historiography) is crucial, since the epic engages in important ways with the different types of explanation in historiographical texts, including explanations of human action or motivation, explanations of events, and explanations of origins or causes, which together account for why things happened as they did in the past, and what effect this has on the present. A historiographical approach to the mythic past can be fruitfully contrasted with modes of explanation more typical of the Argonautica’s key poetic intertexts, such the use of mythical aetiology to authorise connections between past and its present in Pindar’s Pythian 4. It is the combination of elements of both kinds of approach to the past and how to explain it which problematises the connections of past and present in the Argonautica.
What did Herodotus mean for Apollonius’ readers in the Hellenistic period? How did Herodotus affect the historiography written in this period, and what associations did Herodotus have for the audience of Apollonius’ epic? It is to these questions that we turn in this chapter, by examining the relationship of Herodotus to Hellenistic historiography and the wider intellectual culture of the period.
Herodotus thus focuses attention on his own critical faculties and the central role they play in the creation of an authoritative narrative from the material he has himself gathered. Herodotus’ intelligence and judgement are vital if the problems of unreliable or conflicting sources are to be overcome (although Herodotus also shows an acute awareness that sometimes sources present irreducible problems). This too is very different from the Homeric epics, where the problem of sources never arises, since the Muses are presented as having complete omniscience on which the narrator relies absolutely.7 The Homeric narrator never has to establish his own authority as a collector or judge of sources since the Muses’ stories do not require corroboration.8 But Herodotus’ critical attitude to his sources is found throughout the Histories and forms a key element of his distinctively historiographical discourse, thus marked as different in particular from the modes employed in Archaic epic poetry. Herodotus regularly indicates the limits of his knowledge or the boundaries of possible research, as in his statement about the territories inland of those he covers in his account of Scythia.
We have so far examined both how Apollonius exploits general features of the historiographical mode shared by a number of historians and more particularly how he adapts various aspects of Herodotus’ historiographical manner and method; it is also important to focus attention on the various narratives themselves within the Histories and how they are engaged with by the Argonautica. There are several important examples of specific logoi, narratives or locations in Herodotus forming significant reference points for the readers of the epic. These are instances of sections from the text of Herodotus forming a ‘modello-esemplare’ for particular parts of the Argonautica, in which a given section forms the model (or example) on which the Apollonian passage is based.1 Such instances reinforce for the readers of the poem the importance of the broader intertextual relationship between Apollonius’ epic and Herodotus (as both historiographical modello-codice and the modello-esemplare for particular passages), and so lead the readers to expect and look for further examples of interaction with Herodotus (both in terms of specific passages and as a wider reference point as a representative of a type of discourse). Accordingly in this chapter I shall examine particularly important examples of specific interactions with Herodotus and the patterns in the use of these examples which we can discern, especially the importance of Herodotus’ interest in the beginnings of his narrative of Greek/non-Greek conflict) at crucial narrative junctures in Apollonius, and the presence of significant Herodotean places, locations and episodes in the Argonautica. As in the , the implications of the use of Herodotus in this way for reading the Argonautica as containing possible exemplars for Ptolemaic rulers or institutions will be explored.
In fragment 43 of Pfeiffer’s edition of the Aetia (fr. 50 M.), Callimachus has the Muse Clio rest her hand on the shoulder of her sister as she begins to speak for the second time,1 in answer to one of his questions. The sister is unnamed, but it is tempting to think of this as Calliope,2 who probably spoke second of the Muses in the Aetia,3 and was often characterised as the ‘senior Muse’ in ancient texts.4 This vignette hints at the close relationship between epic and historiography, the investigation of which is the subject of this book.5 This closeness has, of course, long been recognised: Herodotus himself was characterised as Ὁμηρικώτατος (‘most Homeric’) by [Longinus] (de subl. 13.3), and modern scholarship has explored at length the Homeric affinities of Herodotean historiography6 so that the roots of historiography in epic are as clear to us as they were for Archelaus of Priene in his Apotheosis of Homer, who depicts History among those sacrificing before the divine Homer, or for the makers of the ‘Salmacis inscription’ which commemorated Herodotus as the ‘Prose Homer of History’.7 The great majority, however, of work on the relationship of historiography and epic has concerned how the former adapts the latter, especially (of course) Homer.8 Less attention has been paid to investigating systematically the degree to which Greek epic after Homer responds to and makes use of the historiography which itself developed and modified various aspects of Homeric epic. There are, however, good reasons for thinking that historiography as a mode of discourse (its tropes, structures, means of characterising individuals, fields of interest), as well as the particular descriptions of places and peoples contained within particular texts, were exploited by Apollonius and other poets. Both epic and history are forms of long, complex narrative, often dealing with the same or similar locations, albeit from different perspectives and with different aims.9 Moreover, the two genres as found in Greek literature were able also to show some important overlap in subject matter and content, since there existed from the Archaic period onwards several examples of epics with a distinct historical dimension, such as the Corinthiaca of Eumelus,10 which connected historical peoples and places with mythic or historical forebears.11
I have argued in this book that in the Argonautica we can see extensive and pervasive engagement with the genre of historiography, in particular with the Histories of Herodotus, which functions both as the modello-codice for historiographical discourse in general and as the particular modello-esemplare for a number of crucial passages in the epic. A good example of this double relationship is provided by the different ways in which Apollonius makes use of Herodotean ethnography, which is among the most distinctive (and influential) aspects of Herodotus’ historical writing. The Argonautica, I have suggested, views the mythological events of the heroic age which it narrates from an ethnographic perspective (quite different from the situation we find in the Homeric epics), in which the narrator explains the practices and customs of heroes such as Jason in a way strongly reminiscent of the kind of language used by Herodotus when explaining the nomoi of historical peoples (both Greek and non-Greek). Particular individual Herodotean descriptions of people, such as those of the Egyptians and Persians, are also engaged with directly by Apollonius in his portrayal of not only non-Greek peoples such as the Colchians, but also in his depiction of Greeks such as Jason. In part, as we have explored, the adoption of an ethnographic perspective and the engagement with particular ethnographies is a means for articulating the Argonautica’s distance from its epic modello-codice, Homer (especially the Odyssey).