Clinical prediction models for diagnosis of COVID-19 among adult patients: a validation and agreement study.

peer reviewed[en] BACKGROUND: Since the beginning of the pandemic, hospitals have been constantly overcrowded, with several observed waves of infected cases and hospitalisations. To avoid as much as possible this situation, efficient tools to facilitate the diagnosis of COVID-19 are needed. OBJECTIVE: To evaluate and compare prediction models to diagnose COVID-19 identified in a systematic review published recently using performance indicators such as discrimination and calibration measures. METHODS: A total of 1618 adult patients present at two Emergency Department triage centers and for whom qRT-PCR tests had been performed were included in this study. Six previously published models were reconstructed and assessed using diagnostic tests as sensitivity (Se) and negative predictive value (NPV), discrimination (Area Under the Roc Curve (AUROC)) and calibration measures. Agreement was also measured between them using Kappa's coefficient and IntraClass Correlation Coefficient (ICC). A sensitivity analysis has been conducted by waves of patients. RESULTS: Among the 6 selected models, those based only on symptoms and/or risk exposure were found to be less efficient than those based on biological parameters and/or radiological examination with smallest AUROC values ( 0.75 for Se and NPV but poor agreement (Kappa and ICC < 0.5) between them. The results of the first wave were similar to those of the second wave. CONCLUSION: Although quite acceptable and similar results were found between all models, the importance of radiological examination was also emphasized, making it difficult to find an appropriate triage system to classify patients at risk for COVID-19

A roadmap to the efficient and robust characterization of temperate terrestrial planet atmospheres with JWST

Ultra-cool dwarf stars are abundant, long-lived, and uniquely suited to enable the atmospheric study of transiting terrestrial companions with JWST. Amongst them, the most prominent is the M8.5V star TRAPPIST-1 and its seven planets, which have been the favored targets of eight JWST Cycle 1 programs. While Cycle 1 observations have started to yield preliminary insights into the planets, they have also revealed that their atmospheric exploration requires a better understanding of their host star. Here, we propose a roadmap to characterize the TRAPPIST-1 system -- and others like it -- in an efficient and robust manner. We notably recommend that -- although more challenging to schedule -- multi-transit windows be prioritized to constrain stellar heterogeneities and gather up to 2$\times$ more transits per JWST hour spent. We conclude that in such systems planets cannot be studied in isolation by small programs, thus large-scale community-supported programs should be supported to enable the efficient and robust exploration of terrestrial exoplanets in the JWST era

A roadmap for the atmospheric characterization of terrestrial exoplanets with JWST

peer reviewedUltracool dwarf stars are abundant, long-lived and uniquely suited to enable the atmospheric study of transiting terrestrial companions with the JWST. Among them, the most prominent is the M8.5V star TRAPPIST-1 and its seven planets. While JWST Cycle 1 observations have started to yield preliminary insights into the planets, they have also revealed that their atmospheric exploration requires a better understanding of their host star. Here we propose a roadmap to characterize the TRAPPIST-1 system — and others like it — in an efficient and robust manner with JWST. We notably recommend that — although more challenging to schedule — multi-transit windows be prioritized to mitigate the effects of stellar activity and gather up to twice more transits per JWST hour spent. We conclude that, for such systems, planets cannot be studied in isolation by small programmes but rather need large-scale, joint space- and ground-based initiatives to fully exploit the capabilities of JWST for the exploration of terrestrial planets

UNRAVELLING THE ROLES OF LYSINE ACETYLATION BY ELP3 DURING INNER EAR DEVELOPMENT

Given the importance of acetylation homeostasis in controlling developmental processes [1-3], we planned to investigate its role in inner ear formation and focused our attention on Elp3 acetyl-transferase, a member of the Elongator complex recently implicated in neurogenesis [4]. To determine the role of Elp3 in the inner ear, we first analysed the spatio-temporal pattern of ELp3 mRNA expression and showed that it was expressed in the entire early otocyst at E11.5 and persisted later in the sensory epithelium of the cochlea (the organ of Corti), in the spiral ganglion, in the stria vascularis and in the vestibule. To unravel in vivo functions of Elp3 in the inner ear, we used conditional knock-out mice in which Elp3 gene is deleted from early otocyst (Elp3 cKO). We submitted these mice to a battery of vestibular testing (i.e. stereotyped circling ambulation, head bobbing, retropulsion, and absence of reaching response in the tail-hanging test) and found significant abnormalities. Besides, the auditory brain stem response of Elp3 cKO indicated that these mice are severely deaf. At the cellular level, we did not find any structural abnormalities nor cell patterning defects that could explain deafness or balance dysfunction in Elp3 cKO mice. However, we detected some defaults in the planar orientation of their auditory hair cell bundle. We were also able to demonstrate an increased level of apoptosis in the Elp3 cKO spiral ganglion at E14.5 leading to a reduced number of neurons and fibers innervating the cochlear hair cells as well as a reduced number of their synaptic ribbons at P15. Moreover, the remaining spiral ganglion neurons extend processes showing clearly defects regarding hair cells innervation (misorientation of fibers). In conclusion, our results clearly show a role for Elp3 both in hearing and balance. We plan to go deeper in the mechanisms involved through the identification of the proteins that are targeted for acetylation by Elp3

Unravelling the roles of lysine acetylation by Elp3 during inner ear development

Given the importance of acetylation homeostasis in controlling developmental processes, we planned to investigate its role in inner ear formation and focused our attention on Elp3 acetyl-transferase, a member of the Elongator complex recently implicated in neurogenesis. To determine the role of Elp3 in the inner ear, we first analysed the spatio-temporal pattern of ELp3 mRNA expression and showed that it was expressed in the entire early otocyst at E11.5 and persisted later in the sensory epithelium of the cochlea (the organ of Corti), in the spiral ganglion, in the stria vascularis and in the vestibule. To unravel in vivo functions of Elp3 in the inner ear, we used conditional knock-out mice in which Elp3 gene is deleted from early otocyst (Elp3 cKO). We submitted these mice to a battery of vestibular testing (i.e. stereotyped circling ambulation, head bobbing, retropulsion, and absence of reaching response in the tail-hanging test) and found significant abnormalities. Besides, the auditory brain stem response of Elp3 cKO indicated that these mice are severely deaf. At the cellular level, we did not find any structural abnormalities nor cell patterning defects that could explain deafness or balance dysfunction in Elp3 cKO mice. However, we detected some defaults in the planar orientation of their auditory hair cell bundle. In addition, the length of the kinocilium was significantly reduced both in vestibular and cochlear hair cells from Elp3 cKO mice compared with wild type littermates. We were also able to demonstrate an increased level of apoptosis in the Elp3 cKO spiral ganglion at E14.5 leading to a reduced number of fibers innervating the cochlear hair cells as well as a reduced number of their synaptic ribbons P15. In conclusion, our results clearly show a role for Elp3 both in hearing and balance. We plan to go deeper in the mechanisms involved through the identification of the proteins that are targeted for acetylation by Elp3

UNRAVELLING THE ROLES OF LYSINE ACETYLATION BY ELP3 DURING INNER EAR DEVELOPMENT

Given the importance of acetylation homeostasis in controlling developmental processes [1-3], we planned to investigate its role in inner ear formation and focused our attention on Elp3 acetyl-transferase, a member of the Elongator complex recently implicated in neurogenesis [4]. To determine the role of Elp3 in the inner ear, we first analysed the spatio-temporal pattern of ELp3 mRNA expression and showed that it was expressed in the entire early otocyst at E11.5 and persisted later in the sensory epithelium of the cochlea (the organ of Corti), in the spiral ganglion, in the stria vascularis and in the vestibule. To unravel in vivo functions of Elp3 in the inner ear, we used conditional knock-out mice in which Elp3 gene is deleted from early otocyst (Elp3 cKO). We submitted these mice to a battery of vestibular testing (i.e. stereotyped circling ambulation, head bobbing, retropulsion, and absence of reaching response in the tail-hanging test) and found significant abnormalities. Besides, the auditory brain stem response of Elp3 cKO indicated that these mice are severely deaf. At the cellular level, we did not find any structural abnormalities nor cell patterning defects that could explain deafness or balance dysfunction in Elp3 cKO mice. However, we detected some defaults in the planar orientation of their auditory hair cell bundle. We were also able to demonstrate an increased level of apoptosis in the Elp3 cKO spiral ganglion at E14.5 leading to a reduced number of neurons and fibers innervating the cochlear hair cells as well as a reduced number of their synaptic ribbons at P15. Moreover, the remaining spiral ganglion neurons extend processes showing clearly defects regarding hair cells innervation (misorientation of fibers). In conclusion, our results clearly show a role for Elp3 both in hearing and balance. We plan to go deeper in the mechanisms involved through the identification of the proteins that are targeted for acetylation by Elp3

Unravelling the roles of lysine acetylation by Elp3 during inner ear development

Given the importance of acetylation homeostasis in controlling developmental processes, we planned to investigate its role in inner ear formation and focused our attention on Elp3 acetyl-transferase, a member of the Elongator complex recently implicated in neurogenesis. To determine the role of Elp3 in the inner ear, we first analysed the spatio-temporal pattern of ELp3 mRNA expression and showed that it was expressed in the entire early otocyst at E11.5 and persisted later in the sensory epithelium of the cochlea (the organ of Corti), in the spiral ganglion, in the stria vascularis and in the vestibule. To unravel in vivo functions of Elp3 in the inner ear, we used conditional knock-out mice in which Elp3 gene is deleted from early otocyst (Elp3 cKO). We submitted these mice to a battery of vestibular testing (i.e. stereotyped circling ambulation, head bobbing, retropulsion, and absence of reaching response in the tail-hanging test) and found significant abnormalities. Besides, the auditory brain stem response of Elp3 cKO indicated that these mice are severely deaf. At the cellular level, we did not find any structural abnormalities nor cell patterning defects that could explain deafness or balance dysfunction in Elp3 cKO mice. However, we detected some defaults in the planar orientation of their auditory hair cell bundle. In addition, the length of the kinocilium was significantly reduced both in vestibular and cochlear hair cells from Elp3 cKO mice compared with wild type littermates. We were also able to demonstrate an increased level of apoptosis in the Elp3 cKO spiral ganglion at E14.5 leading to a reduced number of fibers innervating the cochlear hair cells as well as a reduced number of their synaptic ribbons P15. In conclusion, our results clearly show a role for Elp3 both in hearing and balance. We plan to go deeper in the mechanisms involved through the identification of the proteins that are targeted for acetylation by Elp3

A prospective audit of acute ENT activity in a university teaching hospital

Introduction and aim: Acute ENT coverage is available out-of-hours in most hospitals. However, increasing pressure to reduce healthcare cost threatens this 24-hour availability. Our goal was to audit the emergency ENT activity in our institution. Methods: A prospective audit of all ENT emergency referrals was carried out over a one-month period in an academic hospital. Descriptive statistics were produced for age, sex, origin, admission time, diagnosis, management, and patient outcome. Results: A total of 190 patients (109 men and 81 women) were referred to the ENT emergency service over the study period (mean, 6.1 cases/day). Mean age was 47.9 (SD ±23.6) years. Most admissions (76.4%) occurred during normal working hours, and 62.0% of patients were self-referred. The mean complaint duration before admission was 7.6 (±13.7) days. One third (33.2% patients) required ambulatory treatment, a quarter (24.7% patients) had a minor ENT procedure, 18 (9.5%) required admission to the ward, and 8 (4.2%) required surgical treatment. Severity of diagnosis or management between patients did not differ with referral by a physician (GP or specialist) and self-referral. At 30 days, 3 (1.6%) patients died, 106 (55.8%) benefitted from an ENT follow-up, 65 (34.2%) were referred to another physician (GP or specialist), and 16 (8.4%) were lost to follow-up. Conclusions: The results of this workload audit suggest that emergency ENT activity is justified in our hospital. Restricting emergency ENT cover to patients referred by a GP or another physician would not improve patient selection

Rhinologic Emergencies: a Prospective Audit in a University Teaching Hospital

Aims: Increasing pressure to reduce healthcare cost threatens the provision of acute ENT coverage round the clock. Our goal was to audit our emergency rhinologic activity over a one-month period. Methods: A prospective audit for all emergency ENT referrals was carried out from May 1st to May 31th 2017. Descriptive statistics were produced for age, sex, origin, time of arrival, diagnosis and outcome. A specific subgroup analysis was performed for rhinologic emergencies. A basic cost analysis was ran. Results: Over the study period, 190 patients were referred to the ENT emergency service. Twenty percent patients presented with nose or sinus complaint (36.8% with otological or neuro-vestibular primary complaint, 43.2% with laryngeal or neck complaint). Nose and throat complaints were more likely to present at night or on weekends. Ear complaints were more likely to present during business hours. Rhinologic complaint was more likely to require technical or surgical management than ear or throat complaint. Patients with nose complaint required minor procedure in 43.2% cases (35.6% of the total minor procedures), and required surgical procedure in 13.5% cases. Among the total ENT emergency surgical procedures, 62.5% were rhinologic ones, involving the nose (50%) or the sinus (12.5%). Ear or throat initial complaint were more likely to require no treatment or ambulatory management. Conclusion: The emergency rhinologic activity is justified in our hospital. An initial rhinological complaint was more likely to require specific ENT management than other complaints. ENT cover is an efficient service provision, especially for rhinologic emergencies

Validation and agreement of clinical prediction models for diagnosis of COVID‑19

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