Occupational health screening during Gurkha Central Selection: a retrospective cohort study.

OBJECTIVE: The selection process to the British Army's Brigade of Gurkhas is rigorous, demanding and competitive. The ethos of recruitment to the Gurkhas is grounded in an overarching tenant: that selection is free, fair and transparent. The aim of this study was to retrospectively review reasons for potential recruits (PRs) to be deemed medically unsuitable or deferred suitability on medical grounds for selection to the Brigade of Gurkhas. METHODS: A retrospective review was conducted by extracted data from published post-exercise reports for the past four years to ascertain numbers of PRs deemed medically fit, medically unsuitable or deferred suitability on medical grounds. The International Classification of Disease version 11 (ICD-11) codes were retrospectively assigned to code medical reasons for non-progression. Rates of medical non-progression were compared by year. RESULTS: A total of 3154 PRs were analysed between 2018 and 2021. There was no significant difference between PRs deemed medically fit and those deemed medically suitable or deferred on medical grounds over the study period (p=0.351). There was a significant difference in the ratio of PRs deferred on medical grounds and those deemed medically unsuitable over the study period (p<0.05). CONCLUSION: Selection to the Gurkhas is extremely competitive. These data demonstrate that, overall, reasons for medical deferral or unsuitability have remained constant despite the impact of a global pandemic. These data reinforce the central tenant of Gurkha selection; that it continues to be free, fair, and transparent.

EELS: Autonomous snake-like robot with task and motion planning capabilities for ice world exploration.

Ice worlds are at the forefront of astrobiological interest because of the evidence of subsurface oceans. Enceladus in particular is unique among the icy moons because there are known vent systems that are likely connected to a subsurface ocean, through which the ocean water is ejected to space. An existing study has shown that sending small robots into the vents and directly sampling the ocean water is likely possible. To enable such a mission, NASA's Jet Propulsion Laboratory is developing a snake-like robot called Exobiology Extant Life Surveyor (EELS) that can navigate Enceladus' extreme surface and descend an erupting vent to capture unaltered liquid samples and potentially reach the ocean. However, navigating to and through Enceladus' environment is challenging: Because of the limitations of existing orbital reconnaissance, there is substantial uncertainty with respect to its geometry and the physical properties of the surface/vents; communication is limited, which requires highly autonomous robots to execute the mission with limited human supervision. Here, we provide an overview of the EELS project and its development effort to create a risk-aware autonomous robot to navigate these extreme ice terrains/environments. We describe the robot's architecture and the technical challenges to navigate and sense the icy environment safely and effectively. We focus on the challenges related to surface mobility, task and motion planning under uncertainty, and risk quantification. We provide initial results on mobility and risk-aware task and motion planning from field tests and simulated scenarios.

COVID-19 infection and maternal morbidity in critical care units in Scotland: a national cohort study.

BACKGROUND: Previous research has shown that, in comparison with non-pregnant women of reproductive age, pregnant women with COVID-19 are more likely to be admitted to critical care, receive invasive ventilation, and die. At present there are limited data in relation to outcomes and healthcare utilisation following hospital discharge of pregnant and recently pregnant women admitted to critical care. METHODS: A national cohort study of pregnant and recently pregnant women who were admitted to critical care in Scotland with confirmed or suspected COVID-19. We examined hospital outcomes as well as hospital re-admission rates. RESULTS: Between March 2020 and March 2022, 75 pregnant or recently pregnant women with laboratory-confirmed COVID-19 were admitted to 24 Intensive Care Units across Scotland. Almost two thirds (n=49, 65%) were from the most deprived socio-economic areas. Complete 90-day acute hospital re-admission data were available for 74 (99%) patients. Nine (12%) women required an emergency non-obstetric hospital re-admission within 90 days. Less than 5% of the cohort had received any form of vaccination. CONCLUSIONS: This national cohort study has demonstrated that pregnant or recently pregnant women admitted to critical care with COVID-19 were more likely to reside in areas of socio-economic deprivation, and fewer than 5% of the cohort had received any form of vaccination. More targeted public health campaigning across the socio-economic gradient is urgently required.

Patient engagement in the Continuing Professional Development programs within the department of radiation oncology at the University of Toronto (UTDRO): A qualitative study.

INTRODUCTION: There is little research regarding patient engagement (PE) in Continuing Professional Development (CPD) programs in radiation oncology. This study aims to understand the barriers and enablers to PE in the design and implementation process of CPD programs, and advance PE in these programs moving forward. METHODS: This qualitative study involved 17 semi-structured interviews, with 5 cancer patients and 12 educators, conducted from June 2019 to April 2020. Interview data identified common themes, such as: the current state of PE in CPD programming, and key barriers and recommendations on how to engage patients in meaningful and practical ways. RESULTS: Six themes were identified related to PE: the concept of PE, ethical considerations, barriers, key considerations in planning resources, and the anticipated impact of PE on curriculum planning. CONCLUSION: Both patients and educators emphasized that creating and sustaining meaningful educator-patient relationships and giving patients an active and effective role in CPD planning would improve curriculum content. The University of Toronto Department of Radiation Oncology (UTDRO) should consider building this initiative into its strategic CPD priorities and ensure the appropriate infrastructure is in place.

The changing epidemiology of radial head replacement over a 22-year period in Scotland.

BACKGROUND: Radial head replacement is used to confer joint stability in the management of acute unstable elbow fractures and dislocations associated with instability. We determined the annual incidence of radial head replacement over a 22-year period in a defined population. MATERIALS AND METHODS: Hospital episode statistics were collected prospectively at a national level. This database was retrospectively examined to determine the annual incidence of radial head replacement over the study period in adults over 16 years of age. RESULTS: A total of 615 radial head replacements were performed over the 22 years studied. The overall incidence was 0.65/100,000/year (95% confidence interval, CI, 0.50-0.71). The average adult population during the period was 4,270,593. There was a steady and statistically significant increase in the incidence of radial head replacement over the study period (r 2 = 0.816; p < 0.0001). This incidence was significantly greater in women than men (odds ratio 1.46, 95% CI 1.25-1.72; p < 0.001). The peak incidence in men was 0.87/100,000 population/year in the fifth decade of life while in women the peak incidence was in the seventh decade of life (1.38/100,000 population/year). CONCLUSION: The incidence of radial head replacement has increased steadily over 22 years. We hypothesise that this represents an evolving understanding of the role of radial head replacement in acute trauma in the context of emerging literature during the study period.

Predictors of death and new disability after critical illness: a multicentre prospective cohort study.

PURPOSE: This study aimed to determine the prevalence and predictors of death or new disability following critical illness. METHODS: Prospective, multicentre cohort study conducted in six metropolitan intensive care units (ICU). Participants were adults admitted to the ICU who received more than 24 h of mechanical ventilation. The primary outcome was death or new disability at 6 months, with new disability defined by a 10% increase in the WHODAS 2.0. RESULTS: Of 628 patients with the primary outcome available (median age of 62 [49-71] years, 379 [61.0%] had a medical admission and 370 (58.9%) died or developed new disability by 6 months. Independent predictors of death or new disability included age [OR 1.02 (1.01-1.03), P = 0.001], higher severity of illness (APACHE III) [OR 1.02 (1.01-1.03), P < 0.001] and admission diagnosis. Compared to patients with a surgical admission diagnosis, patients with a cardiac arrest [OR (95% CI) 4.06 (1.89-8.68), P < 0.001], sepsis [OR (95% CI) 2.43 (1.32-4.47), P = 0.004], or trauma [OR (95% CI) 6.24 (3.07-12.71), P < 0.001] diagnosis had higher odds of death or new disability, while patients with a lung transplant [OR (95% CI) 0.21 (0.07-0.58), P = 0.003] diagnosis had lower odds. A model including these three variables had good calibration (Brier score 0.20) and acceptable discriminative power with an area under the receiver operating characteristic curve of 0.76 (95% CI 0.72-0.80). CONCLUSION: Less than half of all patients mechanically ventilated for more than 24 h were alive and free of new disability at 6 months after admission to ICU. A model including age, illness severity and admission diagnosis has acceptable discriminative ability to predict death or new disability at 6 months.

Altered activity patterns during development reduce neural tuning.

Neonatal mice were reared in an acoustic environment that repetitively entrained activity in a large proportion of primary auditory afferents during the period when the frequency tuning of auditory neurons normally develops. The tuning curves obtained from these mice were significantly broader than those of normally reared mice of the same age. This suggests that the normal frequency tuning of neurons was prevented or delayed by synchronizing the pattern of activity imposed on the auditory pathway.

Eye-specific termination bands in tecta of three-eyed frogs.

An extra eye primordium was implanted into the forebrain region of embryonic Rana pipiens. During development both normal and supernumerary optic tracts terminated within a single, previously uninnervated tectal lobe. Autoradiographic tracing of either the normal or supernumerary eye's projection revealed distinct, eye-specific bands of radioactivity running rostrocaudally through the dually innervated tectum. Interactions among axons of retinal ganglion cells, possibly mediated through tectal neurons, must be invoked to explain this stereotyped disruption of the normally continuous retinal termination pattern.

Central projection of optic tract from translocated eyes in the leopard frog (Rana pipiens).

In Rana pipiens embryos, eye anlagen were moved to the evacuated ear position, where they continued to differentiate and sent their optic nerve fibers into the hindbrain. Upon entering the medulla, the optic fibers turned caudally, penetrated the spinal cord, and traversed the dorsolateral white matter to the caudal end. We found this pattern of growth in every animal; the optic fibers did not enter the tecta. These results suggest the existence within the neural tube of a three-dimensional gradient system to which embryonic optic fibers are responsive and which may guide the normal development of the visual pathway.

Clinical practice recommendations for depression.

OBJECTIVE: To provide clinically relevant evidence-based recommendations for the management of depression in adults that are informative, easy to assimilate and facilitate clinical decision making. METHOD: A comprehensive literature review of over 500 articles was undertaken using electronic database search engines (e.g. MEDLINE, PsychINFO and Cochrane reviews). In addition articles, book chapters and other literature known to the authors were reviewed. The findings were then formulated into a set of recommendations that were developed by a multidisciplinary team of clinicians who routinely deal with mood disorders. The recommendations then underwent consultative review by a broader advisory panel that included experts in the field, clinical staff and patient representatives. RESULTS: The clinical practice recommendations for depression (Depression CPR) summarize evidence-based treatments and provide a synopsis of recommendations relating to each phase of the illness. They are designed for clinical use and have therefore been presented succinctly in an innovative and engaging manner that is clear and informative. CONCLUSION: These up-to-date recommendations provide an evidence-based framework that incorporates clinical wisdom and consideration of individual factors in the management of depression. Further, the novel style and practical approach should promote uptake and implementation.

Clinical practice recommendations for bipolar disorder.

OBJECTIVE: To provide clinically relevant evidence-based recommendations for the management of bipolar disorder in adults that are informative, easy to assimilate and facilitate clinical decision-making. METHOD: A comprehensive literature review of over 500 articles was undertaken using electronic database search engines (e.g. MEDLINE, PsychINFO and Cochrane reviews). In addition articles, book chapters and other literature known to the authors were reviewed. The findings were then formulated into a set of recommendations that were developed by a multidisciplinary team of clinicians who routinely deal with mood disorders. These preliminary recommendations underwent extensive consultative review by a broader advisory panel that included experts in the field, clinical staff and patient representatives. RESULTS: The clinical practice recommendations for bipolar disorder (bipolar CPR) summarise evidence-based treatments and provide a synopsis of recommendations relating to each phase of the illness. They are designed for clinical use and have therefore been presented succinctly in an innovative and engaging manner that is clear and informative. CONCLUSION: These up-to-date recommendations provide an evidence-based framework that incorporates clinical wisdom and consideration of individual factors in the management of bipolar disorder. Further, the novel style and practical approach should promote their uptake and implementation.

NMDA receptor antagonists disrupt the retinotectal topographic map.

We tested the effect of two NMDA receptor antagonists, APV or MK801 (with NMDA), and the receptor agonist NMDA on the maintenance of retinal topography in frogs. Topography was assayed by measuring the dispersion of retrogradely labeled ganglion cells following a local HRP injection into the tectum. In untreated tadpoles, labeled cells covered about 5% of the retinal area. In APV- or MK801/NMDA-treated tadpoles, labeled ganglion cells covered 17% and 10% of the retinal area, respectively. Neither treatment with L-APV nor with NMDA disrupts the fidelity of the retinotectal projection. Neither APV- nor NMDA-treated ganglion cell terminals differed from untreated terminals with respect to tangential area, branch number, or branch density. These data support a role for the NDMA receptor in visual system development.

The differential influence of protein kinase inhibitors on retinal arbor morphology and eye-specific stripes in the frog retinotectal system.

We investigated retinal axon morphology and eye-specific afferent termination zones in the optic tectum of three-eyed tadpoles that were chronically treated with protein kinase inhibitors. The kinase inhibitors sphingosine, H-7, and phorbol ester, which down-regulates protein kinase C with chronic exposure, were applied to the tecta in a slow release plastic, Elvax. In vivo protein phosphorylation assays in drug-treated tadpoles indicated that the treatments decreased 32P incorporation into some protein bands by as much as 60%. Although the drugs did not cause a desegregation of the eye-specific stripes, treated retinal axon arbors covered about half the area covered by untreated arbors or arbors treated with inactive analogs of the drugs. We conclude that eye-specific segregation can be maintained under conditions that markedly alter retinal ganglion cell axon arbor size and that significantly perturb protein phosphorylation. Furthermore, we conclude that the protein kinase(s) that we blocked with these treatments is involved in the growth of axon arbors.

Activity-dependent induction of tonic calcineurin activity mediates a rapid developmental downregulation of NMDA receptor currents.

Whole-cell recording in the superficial layers of the developing superior colliculus (sSC) reveals a large drop in NMDA receptor (NMDAR) current decay time synchronized across all neurons and occurring consistently between P10 and P11. We show that blocking the Ca2+/calmodulin-dependent phosphatase calcineurin (CaN) in the postsynaptic neuron can abolish this drop. The regulation is induced prematurely by 1-2 hr of electrical stimulation in P10 collicular slices only if CaN and NMDAR currents can be activated in the neuron. These data suggest that a long-lasting, CaN-mediated control of NMDAR kinetics is rapidly initiated by heightened activity of the NMDAR itself and demonstrate a novel developmental and tonic function of CaN that can play an important role in modulating the plasticity of the developing CNS.

NMDA receptor-mediated control of protein synthesis at developing synapses.

We demonstrate a rapid and complex effect of N-methyl-d-aspartate receptor (NMDAR) activation on synaptic protein synthesis in the superior colliculi of young rats. Within minutes of receptor activation, translation of alpha Ca2+/calmodulin dependent kinase II (alphaCamK II) was increased, whereas total protein synthesis was reduced. NMDAR activation also increased phosphorylation of eukaryotic elongation factor 2 (eEF2), a process known to inhibit protein translation by reducing peptide chain elongation. Low doses of cycloheximide, which reduce elongation rate independently of eEF2 phosphorylation, decreased overall protein synthesis but increased alphaCaMK II synthesis. These observations suggest that regulation of peptide elongation via eEF2 phosphorylation can link NMDAR activation to local increases in the synthesis of specific proteins during activity-dependent synaptic change.

LTP and activity-dependent synaptogenesis: the more alike they are, the more different they become.

Recent data suggest that long-term potentiation and activity-dependent synaptogenesis share the same mechanism at the initiation stage during which NMDA receptor activity is necessary to increase the postsynaptic response via AMPA receptor currents. However, several fundamental differences between the environments of young and mature synapses and the neurons that support them suggest that the same cellular mechanism is facilitated by very different parameters in the young versus the mature brain.

Nitric oxide in the retinotectal system: a signal but not a retrograde messenger during map refinement and segregation.

The role of nitric oxide (NO) as a mediator of synaptic plasticity is controversial in both the adult and developing brain. NO generation appears to be necessary for some types of NMDA receptor-dependent synaptic plasticity during development but not for others. Our previous work using several NO donors revealed that Xenopus laevis retinal ganglion cell axons stop growing in response to NO exposure. We demonstrate here that the same response occurs in tectal neuron processes bathed in the NO donor S-nitrosocysteine (SNOC) and in RGC growth cones to which SNOC is very locally applied. We show that NO synthase (NOS) activity is present in the Rana pipiens optic tectum throughout development in a dispersed subpopulation of tectal neurons, although effects of NO on synaptic function in a Rana pipiens tectal slice were varied. We chronically inhibited NOS in doubly innervated Rana tadpole optic tecta using L-N(G)-nitroarginine methyl ester in Elvax. Despite significant NOS inhibition as measured biochemically, eye-specific stripes remained normally segregated. This suggests that NOS activity is not downstream of NMDA receptor activation during retinotectal synaptic competition because NMDA receptor activation is necessary for segregation of retinal afferents into ocular dominance stripes in the doubly innervated tadpole optic tectum. We conclude that NO has some signaling function in the retinotectal pathway, but this function is not critical to the mechanism that refines the projection and causes eye-specific stripes.

Chronic NMDA receptor blockade from birth increases the sprouting capacity of ipsilateral retinocollicular axons without disrupting their early segregation.

We have investigated the role of the NMDA glutamate receptor (NMDAR) in the genesis and regulation of structural plasticity during synaptogenesis in the visual layers of the rat superior colliculus (sSC). In this neuropil, three projections compete for synaptic space during development. By fluorescently labeling the projections of both eyes and imaging them with confocal microscopy, we can quantify the sprouting of the ipsilateral retinal projection that follows removal of a portion of the contralateral retinal and/or corticocollicular projection. Using these techniques we have studied the effects of NMDAR blockade under different levels of competition. NMDARs were chronically blocked from birth [postnatal day 0 (P0)] by suspending the competitive antagonist 2-amino-5-phosphonopentanoic acid in the slow release plastic Elvax, a slab of which was implanted over the sSC. Such treatment alone does not impair the normal segregation of the retinal projections. However, if sprouting of the ipsilateral projection is initiated with a small contralateral retinal lesion at P6, this sprouting can be further increased by blocking NMDARs from birth. Sprouting of the ipsilateral retinal projection is also induced by retinal lesions made at P10/P11, but NMDAR blockade does not augment the sprouting induced by this later lesion. However, when combined with simultaneous ablation of the ipsilateral visual cortex, P10/P11 lesions show increased sprouting after NMDAR blockade. These data indicate that P0 NMDAR blockade does not eliminate synaptic competition in the sSC. Instead, early elimination of NMDAR function appears to facilitate sprouting that is gated in a stepwise manner by the other visual afferents.

Developmental depression of glutamate neurotransmission by chronic low-level activation of NMDA receptors.

Slabs of slow-release plastic (Elvax) containing NMDA or solvent were implanted over the rat colliculus beginning on postnatal day 8 (P8). Whole-cell patch clamping in the superficial superior collicular layers (sSCs) from P10 to P21 demonstrated a severe decrease in spontaneous EPSC frequency after chronic NMDA treatment. The decrease was not attributable to an increase in GABA(A) receptor-mediated inhibition and was present only when NMDA receptor (NMDAR) current was blocked by Mg(2+). Analysis of miniature EPSCs indicated that many active sites on NMDA-treated neurons lacked functional AMPA and kainate receptor (AMPA/KAR) currents, and AMPA/KAR:NMDAR current ratios of evoked EPSCs were also significantly reduced. In addition, the normal downregulation of NMDAR decay time in sSC neurons at P11 was absent after NMDA treatment. Nevertheless, neither AMPA nor NMDA receptor subunit expression was altered by NMDA treatment, and experiments with the NMDAR antagonist ifenprodil suggested that incorporation of NR2A-containing NMDARs at the sSC synapses was unperturbed. Thus, disrupting but not blocking NMDARs suppresses the development of AMPA/KAR currents. The absence of the P11 NMDAR current downregulation is likely a secondary effect resulting from the reduction of AMPA/KAR function. Chronic agonist application reduces but does not eliminate NMDAR conductances. Therefore these data support an active role for NMDAR currents in synaptic development. Prolonged NMDA treatment in vivo, which couples reduced postsynaptic Ca(2+) responses with normally developing afferent activity, produces a long-lasting synaptic depression and stalls glutamatergic synaptogenesis, suggesting that the correlation between robust NMDAR activation and afferent activity is an essential component during normal development.