79 research outputs found

    Academic anaesthesiology: a global perspective on training, support, and future development of early career researchers

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    As anaesthesiologists face increasing clinical demands and a limited and competitive funding environment for academic work, the sustainability of academic anaesthesiologists has never been more tenuous. Yet, the speciality needs academic anaesthesiologists in many roles, extending beyond routine clinical duties. Anaesthesiologist educators, researchers, and administrators are required not only to train future generations but also to lead innovation and expansion of anaesthesiology and related specialities, all to improve patient care. This group of early career researchers with geographically distinct training and practice backgrounds aim to highlight the diversity in clinical and academic training and career development pathways for anaesthesiologists globally. Although multiple routes to success exist, one common thread is the need for consistent support of strong mentors and sponsors. Moreover, to address inequitable opportunities, we emphasise the need for diversity and inclusivity through global collaboration and exchange that aims to improve access to research training and participation. We are optimistic that by focusing on these fundamental principles, we can help build a more resilient and sustainable future for academic anaesthesiologists around the world

    Chiral Supergravity

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    We study the linearized approximation of N=1 topologically massive supergravity around AdS3. Linearized gravitino fields are explicitly constructed. For appropriate boundary conditions, the conserved charges demonstrate chiral behavior, so that chiral gravity can be consistently extended to chiral supergravity.Comment: 30 page

    Coordinating Tissue Regeneration Through Transforming Growth Factorâ β Activated Kinase 1 Inactivation and Reactivation

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    Aberrant wound healing presents as inappropriate or insufficient tissue formation. Using a model of musculoskeletal injury, we demonstrate that loss of transforming growth factorâ β activated kinase 1 (TAK1) signaling reduces inappropriate tissue formation (heterotopic ossification) through reduced cellular differentiation. Upon identifying increased proliferation with loss of TAK1 signaling, we considered a regenerative approach to address insufficient tissue production through coordinated inactivation of TAK1 to promote cellular proliferation, followed by reactivation to elicit differentiation and extracellular matrix production. Although the current regenerative medicine paradigm is centered on the effects of drug treatment (â drug onâ ), the impact of drug withdrawal (â drug offâ ) implicit in these regimens is unknown. Because current TAK1 inhibitors are unable to phenocopy genetic Tak1 loss, we introduce the dualâ inducible COmbinational Sequential Inversion ENgineering (COSIEN) mouse model. The COSIEN mouse model, which allows us to study the response to targeted drug treatment (â drug onâ ) and subsequent withdrawal (â drug offâ ) through genetic modification, was used here to inactivate and reactivate Tak1 with the purpose of augmenting tissue regeneration in a calvarial defect model. Our study reveals the importance of both the â drug onâ (Creâ mediated inactivation) and â drug offâ (Flpâ mediated reactivation) states during regenerative therapy using a mouse model with broad utility to study targeted therapies for disease. Stem Cells 2019;37:766â 778Manipulating transforming growth factor βâ activated kinase 1 for cell and scaffold free tissue regeneration using a dualâ inducible Combinational Sequential Inversion Engineering mouse model.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149573/1/stem2991_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149573/2/stem2991.pd

    Effects of Cocaine-Kindling on the Expression of NMDA Receptors and Glutamate Levels in Mouse Brain

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    In the present study we examined the effects of cocaine seizure kindling on the expression of NMDA receptors and levels of extracellular glutamate in mouse brain. Quantitative autoradiography did not reveal any changes in binding of [3H] MK-801 to NMDA receptors in several brain regions. Likewise, in situ hybridization and Western blotting revealed no alteration in expression of the NMDA receptor subunits, NR1 and NR2B. Basal overflow of glutamate in the ventral hippocampus determined by microdialysis in freely moving animals also did not differ between cocaine-kindled and control groups. Perfusion with the selective excitatory amino acid transporter inhibitor, pyrrolidine-2,4-dicarboxylic acid (tPDC, 0.6 mM), increased glutamate overflow confirming transport inhibition. Importantly, KCl-evoked glutamate overflow under tPDC perfusion was significantly higher in cocaine-kindled mice than in control mice. These data suggest that enhancement of depolarization stimulated glutamate release may be one of the mechanisms underlying the development of increased seizure susceptibility after cocaine kindling

    Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

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    BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

    Family-led rehabilitation after stroke in India (ATTEND): a randomised controlled trial

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    Background Most people with stroke in India have no access to organised rehabilitation services. The effectiveness of training family members to provide stroke rehabilitation is uncertain. Our primary objective was to determine whether family-led stroke rehabilitation, initiated in hospital and continued at home, would be superior to usual care in a low-resource setting. Methods The Family-led Rehabilitation after Stroke in India (ATTEND) trial was a prospectively randomised open trial with blinded endpoint done across 14 hospitals in India. Patients aged 18 years or older who had had a stroke within the past month, had residual disability and reasonable expectation of survival, and who had an informal family-nominated caregiver were randomly assigned to intervention or usual care by site coordinators using a secure web-based system with minimisation by site and stroke severity. The family members of participants in the intervention group received additional structured rehabilitation training—including information provision, joint goal setting, carer training, and task-specific training—that was started in hospital and continued at home for up to 2 months. The primary outcome was death or dependency at 6 months, defined by scores 3–6 on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) as assessed by masked observers. Analyses were by intention to treat. This trial is registered with Clinical Trials Registry-India (CTRI/2013/04/003557), Australian New Zealand Clinical Trials Registry (ACTRN12613000078752), and Universal Trial Number (U1111-1138-6707). Findings Between Jan 13, 2014, and Feb 12, 2016, 1250 patients were randomly assigned to intervention (n=623) or control (n=627) groups. 33 patients were lost to follow-up (14 intervention, 19 control) and five patients withdrew (two intervention, three control). At 6 months, 285 (47%) of 607 patients in the intervention group and 287 (47%) of 605 controls were dead or dependent (odds ratio 0·98, 95% CI 0·78–1·23, p=0·87). 72 (12%) patients in the intervention group and 86 (14%) in the control group died (p=0·27), and we observed no difference in rehospitalisation (89 [14%]patients in the intervention group vs 82 [13%] in the control group; p=0·56). We also found no difference in total non-fatal events (112 events in 82 [13%] intervention patients vs 110 events in 79 [13%] control patients; p=0·80). Interpretation Although task shifting is an attractive solution for health-care sustainability, our results do not support investment in new stroke rehabilitation services that shift tasks to family caregivers, unless new evidence emerges. A future avenue of research should be to investigate the effects of task shifting to health-care assistants or team-based community care

    Diagnosing nasal obstruction and its common causes using the nasal acoustic device: A pilot study

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    Objectives: There is a need to develop a medical device which can accurately measure normal and abnormal nasal breathing which the patient can better understand in addition to being able to diagnose the cause for their nasal obstruction. The aim is to evaluate the accuracy of the nasal acoustic device (NAD) in diagnosing the common causes for nasal obstruction and diagnosing normal and abnormal (nasal obstruction) nasal breathing. Methods: This pilot study recruited 27 patients with allergic rhinitis (AR), chronic rhinosinusitis (CRS), and a deviated nasal septum (DNS) which represents the common causes for NO and 26 controls (with normal nasal breathing). Nasal breathing sounds were recorded by the NAD akin to two small stethoscopes placed over the left and right nasal ala. The novel outcome metrics for the NAD include inspiratory nasal acoustic score (INA) score, expiratory nasal acoustic (ENA) score and the inspiratory nasal obstruction balance index (NOBI). The change in acoustic score following decongestant is key in this diagnostic process. Results: Pre‐decongestant ENA score was used to detect the presence of nasal obstruction in patients compared to controls, with a sensitivity of 0.81 (95% CI: 0.66‐0.96) and a specificity of 0.77 (0.54‐1.00). Post‐decongestant percentage change in INA score was used to identify the presence of AR or CRS, with a sensitivity of 0.87 (0.69‐1.00) and specificity of 0.72 (0.55‐0.89) for AR; and a sensitivity of 0.92 (0.75‐1.00) and specificity of 0.69 (0.52‐0.86) for CRS. Post‐decongestant inspiratory NOBI was used to identify DNS, with a sensitivity of 0.77 (0.59‐0.95) and specificity of 0.94 (0.82‐1.00). Conclusion: We have demonstrated that the NAD can help distinguish between normal and abnormal nasal breathing and help diagnose AR, CRS, and DNS. Such a device has not been invented and could revolutionize COVID‐19 recovery telemedicine. Level of Evidence: Diagnostic accuracy study—Level III
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