Standard Anatomical and Visual Space for the Mouse Retina: Computational Reconstruction and Transformation of Flattened Retinae with the Retistruct Package

The concept of topographic mapping is central to the understanding of the visual system at many levels, from the developmental to the computational. It is important to be able to relate different coordinate systems, e.g. maps of the visual field and maps of the retina. Retinal maps are frequently based on flat-mount preparations. These use dissection and relaxing cuts to render the quasi-spherical retina into a 2D preparation. The variable nature of relaxing cuts and associated tears limits quantitative cross-animal comparisons. We present an algorithm, "Retistruct," that reconstructs retinal flat-mounts by mapping them into a standard, spherical retinal space. This is achieved by: stitching the marked-up cuts of the flat-mount outline; dividing the stitched outline into a mesh whose vertices then are mapped onto a curtailed sphere; and finally moving the vertices so as to minimise a physically-inspired deformation energy function. Our validation studies indicate that the algorithm can estimate the position of a point on the intact adult retina to within 8° of arc (3.6% of nasotemporal axis). The coordinates in reconstructed retinae can be transformed to visuotopic coordinates. Retistruct is used to investigate the organisation of the adult mouse visual system. We orient the retina relative to the nictitating membrane and compare this to eye muscle insertions. To align the retinotopic and visuotopic coordinate systems in the mouse, we utilised the geometry of binocular vision. In standard retinal space, the composite decussation line for the uncrossed retinal projection is located 64° away from the retinal pole. Projecting anatomically defined uncrossed retinal projections into visual space gives binocular congruence if the optical axis of the mouse eye is oriented at 64° azimuth and 22° elevation, in concordance with previous results. Moreover, using these coordinates, the dorsoventral boundary for S-opsin expressing cones closely matches the horizontal meridian

The Australasian Resuscitation In Sepsis Evaluation : fluids or vasopressors in emergency department sepsis (ARISE FLUIDS), a multi-centre observational study describing current practice in Australia and New Zealand

Objectives: To describe haemodynamic resuscitation practices in ED patients with suspected sepsis and hypotension. Methods: This was a prospective, multicentre, observational study conducted in 70 hospitals in Australia and New Zealand between September 2018 and January 2019. Consecutive adults presenting to the ED during a 30-day period at each site, with suspected sepsis and hypotension (systolic blood pressure <100 mmHg) despite at least 1000 mL fluid resuscitation, were eligible. Data included baseline demographics, clinical and laboratory variables and intravenous fluid volume administered, vasopressor administration at baseline and 6- and 24-h post-enrolment, time to antimicrobial administration, intensive care admission, organ support and in-hospital mortality. Results: A total of 4477 patients were screened and 591 were included with a mean (standard deviation) age of 62 (19) years, Acute Physiology and Chronic Health Evaluation II score 15.2 (6.6) and a median (interquartile range) systolic blood pressure of 94 mmHg (87–100). Median time to first intravenous antimicrobials was 77 min (42–148). A vasopressor infusion was commenced within 24 h in 177 (30.2%) patients, with noradrenaline the most frequently used (n = 138, 78%). A median of 2000 mL (1500–3000) of intravenous fluids was administered prior to commencing vasopressors. The total volume of fluid administered from pre-enrolment to 24 h was 4200 mL (3000–5661), with a range from 1000 to 12 200 mL. Two hundred and eighteen patients (37.1%) were admitted to an intensive care unit. Overall in-hospital mortality was 6.2% (95% confidence interval 4.4–8.5%). Conclusion: Current resuscitation practice in patients with sepsis and hypotension varies widely and occupies the spectrum between a restricted volume/earlier vasopressor and liberal fluid/later vasopressor strategy

Functional topography and integration of the contralateral and ipsilateral retinocollicular projections of ephrin-A-/- mice.

Topographically ordered projections are established by molecular guidance cues and refined by neuronal activity. Retinal input to a primary visual center, the superior colliculus (SC), is bilateral with a dense contralateral projection and a sparse ipsilateral one. Both projections are topographically organized, but in opposing anterior-posterior orientations. This arrangement provides functionally coherent input to each colliculus from the binocular visual field, supporting visual function. When guidance cues involved in contralateral topography (ephrin-As) are absent, crossed retinal ganglion cell (RGC) axons form inappropriate terminations within the SC. However, the organization of the ipsilateral projection relative to the abnormal contralateral input remains unknown, as does the functional capacity of both projections. We show here that in ephrin-A(-/-) mice, the SC contains an expanded, diffuse ipsilateral projection. Electrophysiological recording demonstrated that topography of visually evoked responses recorded from the contralateral superior colliculus of ephrin-A(-/-) mice displayed similar functional disorder in all genotypes, contrasting with their different degrees of anatomical disorder. In contrast, ipsilateral responses were retinotopic in ephrin-A2(-/-) but disorganized in ephrin-A2/A5(-/-) mice. The lack of integration of binocular input resulted in specific visual deficits, which could be reversed by occlusion of one eye. The discrepancy between anatomical and functional topography in both the ipsilateral and contralateral projections implies suppression of inappropriately located terminals. Moreover, the misalignment of ipsilateral and contralateral visual information in ephrin-A2/A5(-/-) mice suggests a role for ephrin-As in integrating convergent visual inputs

Effect of lower vs higher oxygen saturation targets on survival to hospital discharge among patients resuscitated after out-of-hospital cardiac arrest

ImportanceThe administration of a high fraction of oxygen following return of spontaneous circulation in out-of-hospital cardiac arrest may increase reperfusion brain injury.ObjectiveTo determine whether targeting a lower oxygen saturation in the early phase of postresuscitation care for out-of-hospital cardiac arrest improves survival at hospital discharge.Design, Setting, and ParticipantsThis multicenter, parallel-group, randomized clinical trial included unconscious adults with return of spontaneous circulation and a peripheral oxygen saturation (Spo2) of at least 95% while receiving 100% oxygen. The trial was conducted in 2 emergency medical services and 15 hospitals in Victoria and South Australia, Australia, between December 11, 2017, and August 11, 2020, with data collection from ambulance and hospital medical records (final follow-up date, August 25, 2021). The trial enrolled 428 of a planned 1416 patients.InterventionsPatients were randomized by paramedics to receive oxygen titration to achieve an oxygen saturation of either 90% to 94% (intervention; n = 216) or 98% to 100% (standard care; n = 212) until arrival in the intensive care unit.Main Outcomes and MeasuresThe primary outcome was survival to hospital discharge. There were 9 secondary outcomes collected, including hypoxic episodes (Spo2 &amp;amp;lt;90%) and prespecified serious adverse events, which included hypoxia with rearrest.ResultsThe trial was stopped early due to the COVID-19 pandemic. Of the 428 patients who were randomized, 425 were included in the primary analysis (median age, 65.5 years; 100 [23.5%] women) and all completed the trial. Overall, 82 of 214 patients (38.3%) in the intervention group survived to hospital discharge compared with 101 of 211 (47.9%) in the standard care group (difference, −9.6% [95% CI, −18.9% to −0.2%]; unadjusted odds ratio, 0.68 [95% CI, 0.46-1.00]; P = .05). Of the 9 prespecified secondary outcomes collected during hospital stay, 8 showed no significant difference. A hypoxic episode prior to intensive care was observed in 31.3% (n = 67) of participants in the intervention group and 16.1% (n = 34) in the standard care group (difference, 15.2% [95% CI, 7.2%-23.1%]; OR, 2.37 [95% CI, 1.49-3.79]; P &amp;amp;lt; .001).Conclusions and RelevanceAmong patients achieving return of spontaneous circulation after out-of-hospital cardiac arrest, targeting an oxygen saturation of 90% to 94%, compared with 98% to 100%, until admission to the intensive care unit did not significantly improve survival to hospital discharge. Although the trial is limited by early termination due to the COVID-19 pandemic, the findings do not support use of an oxygen saturation target of 90% to 94% in the out-of-hospital setting after resuscitation from cardiac arrest.Trial RegistrationClinicalTrials.gov Identifier: NCT0313800