A macroscopic free-swimming medusa from the middle Cambrian Burgess Shale.

Cnidarians are regarded as one of the earliest-diverging animal phyla. One of the hallmarks of the cnidarian body plan is the evolution of a free-swimming medusa in some medusozoan classes, but the origin of this innovation remains poorly constrained by the fossil record and molecular data. Previously described macrofossils, putatively representing medusa stages of crown-group medusozoans from the Cambrian of Utah and South China, are here reinterpreted as ctenophore-grade organisms. Other putative Ediacaran to Cambrian medusozoan fossils consist mainly of microfossils and tubular forms. Here we describe Burgessomedusa phasmiformis gen. et sp. nov., the oldest unequivocal macroscopic free-swimming medusa in the fossil record. Our study is based on 182 exceptionally preserved body fossils from the middle Cambrian Burgess Shale (Raymond Quarry, British Columbia, Canada). Burgessomedusa possesses a cuboidal umbrella up to 20 cm high and over 90 short, finger-like tentacles. Phylogenetic analysis supports a medusozoan affinity, most likely as a stem group to Cubozoa or Acraspeda (a group including Staurozoa, Cubozoa and Scyphozoa). Burgessomedusa demonstrates an ancient origin for the free-swimming medusa life stage and supports a growing number of studies showing an early evolutionary diversification of Medusozoa, including of the crown group, during the late Precambrian-Cambrian transition.

First record of growth patterns in a Cambrian annelid.

Early annelid evolution is mostly known from 13 described species from Cambrian Burgess Shale-type Lagerstätten. We introduce a new exceptionally well-preserved polychaete, Ursactis comosa gen. et sp. nov., from the Burgess Shale (Wuliuan Stage). This small species (3-15 mm) is the most abundant Cambrian polychaete known to date. Most specimens come from Tokumm Creek, a new Burgess Shale locality in northern Kootenay National Park, British Columbia, Canada. Ursactis has a pair of large palps, thin peristomial neurochaetae and biramous parapodia bearing similarly sized capillary neurochaetae and notochaetae, except for segments six to nine, which also have longer notochaetae. The number of segments in this polychaete range between 8 and 10 with larger individuals having 10 segments. This number of segments in Ursactis is remarkably small compared with other polychaetes, including modern forms. Specimens with 10 segments show significant size variations, and the length of each segment increases with the body length, indicating that body growth was primarily achieved by increasing the size of existing segments rather than adding new ones. This contrasts with most modern polychaetes, which typically have a larger number of segments through additions of segments throughout life. The inferred growth pattern in Ursactis suggests that annelids had evolved control over segment addition by the mid-Cambrian.

Childhood maltreatment and major depressive disorder in well-being: a network analysis of a longitudinal community-based cohort.

BACKGROUND: Little has been done to comprehensively study the relationships between multiple well-being constructs at a time. Even less is known about whether child maltreatment and major depressive disorder (MDD) impact different well-being constructs. This study aims to examine whether maltreated or depressed individuals have specific impacts on well-being structures. METHODS: Data analyzed were from the Montreal South-West Longitudinal Catchment Area Study (N = 1380). The potential confounding of age and sex was controlled by propensity score matching. We used network analysis to assess the impact of maltreatment and MDD on well-being. The centrality of nodes was estimated with the 'strength' index and a case-dropping bootstrap procedure was used to test network stability. Differences in the structure and connectivity of networks between different studied groups were also examined. RESULTS: Autonomy and daily life and social relations were the most central nodes for the MDD and maltreated groups [MDD group: strength coefficient (SC) autonomy = 1.50; SCdaily life and social relations = 1.34; maltreated group: SCautonomy = 1.69; SCdaily life and social relations = 1.55]. Both maltreatment and MDD groups had statistical differences in terms of the global strength of interconnectivity in their networks. Network invariance differed between with and without MDD groups indicating different structures of their networks. The non-maltreatment and MDD group had the highest level of overall connectivity. CONCLUSIONS: We discovered distinct connectivity patterns of well-being outcomes in maltreatment and MDD groups. The identified core constructs could serve as potential targets to maximize the effectiveness of clinical management of MDD and also advance prevention to minimize the sequelae of maltreatment.

The problematic Cambrian arthropod Tuzoia and the origin of mandibulates revisited.

The origin of mandibulates, the hyperdiverse arthropod group that includes pancrustaceans and myriapods, dates back to the Cambrian. Bivalved arthropod groups such as hymenocarines have been argued to be early mandibulates, but many species are still poorly known, and their affinities remain uncertain. One of the most common and globally distributed Cambrian bivalved arthropods is Tuzoia. Originally described in 1912 from the Burgess Shale based on isolated carapaces, its full anatomy has remained largely unknown. Here, we describe new specimens of Tuzoia from the Canadian Burgess Shale (Wuliuan, Cambrian) showcasing exceptionally preserved soft tissues, allowing for the first comprehensive reconstruction of its anatomy, ecology and evolutionary affinities. The head bears antennae and differentiated cephalic appendages. The body is divided into a cephalothorax, a homonomous trunk bearing ca 10 pairs of legs with heptopodomerous endopods and enlarged basipods, and a tail fan with two pairs of caudal rami. These traits suggest that Tuzoia swam along the seafloor and used its spinose legs for predation or scavenging. Tuzoia is retrieved by a Bayesian phylogenetic analysis as an early mandibulate hymenocarine lineage, exemplifying the rapid diversification of this group in open marine environments during the Cambrian Explosion.

To what extent do social support and coping strategies mediate the relation between childhood maltreatment and major depressive disorder: A longitudinal community-based cohort.

This study aimed to articulate the roles of social support and coping strategies in the relation between childhood maltreatment (CM) and subsequent major depressive disorder (MDD) with a comprehensive exploration of potential factors in a longitudinal community-based cohort. Parallel and serial mediation analyses were applied to estimate the direct effect (DE) (from CM to MDD) and indirect effects (from CM to MDD through social support and coping strategies, simultaneously and sequentially). Sociodemographic characteristics and genetic predispositions of MDD were considered in the modeling process. A total of 902 participants were included in the analyses. CM was significantly associated with MDD (DE coefficient (ß) = 0.015, 95% confidence interval (CI) = 0.002∼0.028). This relation was partially mediated by social support (indirect ß = 0.004, 95% CI = 0.0001∼0.008) and negative coping (indirect ß = 0.013, 95% CI = 0.008∼0.020), respectively. Social support, positive coping, and negative coping also influenced each other and collectively mediated the association between CM and MDD. This study provides robust evidence that although CM has a detrimental effect on later-on MDD, social support and coping strategies could be viable solutions to minimize the risk of MDD. Intervention and prevention programs should primarily focus on weakening negative coping strategies, then strengthening social support and positive coping strategies.

A possible home for a bizarre Carboniferous animal: is Typhloesus a pelagic gastropod?

By contrast to many previously enigmatic Palaeozoic fossils, the Carboniferous metazoan Typhloesus has defied phylogenetic placement. Here, we document new features, including possible phosphatized muscle tissues and a hitherto unrecognized feeding apparatus with two sets of ca 20 spinose teeth whose closest similarities appear to lie with the molluscan radula. The ribbon-like structure, located well behind the mouth area and deep into the anterior part of the body, is interpreted as being in an inverted proboscis configuration. Gut contents, mostly conodonts, in the midgut area demonstrate that Typhloesus was an active predator. This animal was capable of propelling itself in the water column using its flexible body and a prominent posterior fin. The affinity of Typhloesus as a pelagic mollusc remains problematic but may lie more closely with the gastropods. Heteropod gastropods share with Typhloesus an active predatory lifestyle and have a comparable general body organization, albeit they possess characteristic aragonitic shells and their origins in the Jurassic post-date Typhloesus. Typhloesus may represent an independent radiation of Mid-Palaeozoic pelagic gastropods.

A three-eyed radiodont with fossilized neuroanatomy informs the origin of the arthropod head and segmentation.

In addition to being among the most iconic and bizarre-looking Cambrian animals, radiodonts are a group that offers key insight into the acquisition of the arthropod body plan by virtue of their phylogenetic divergence prior to all living members of the phylum. Nonetheless, radiodont fossils are rare and often fragmentary, and contentions over their interpretation have hindered resolution of important evolutionary conundrums. Here, we describe 268 specimens of Stanleycaris hirpex from the Cambrian Burgess Shale, including many exceptionally preserved whole-body specimens, informing the most complete reconstruction of a radiodont to date. The trunk region of Stanleycaris has up to 17 segments plus two pairs of filiform caudal blades. The recognition of dorsal sclerotic segmentation of the trunk cuticle and putative unganglionated nerve cords provides new insight into the relative timing of acquisition of segmental traits, the epitome of the arthropod body plan. In addition to the pair of stalked lateral eyes, the short head unexpectedly bears a large median eye situated behind a preocular sclerite on an anteriorly projecting head lobe. Upon re-evaluation, similar median eyes can be identified in other Cambrian panarthropods demonstrating a deep evolutionary continuity. The exquisitely preserved brain of Stanleycaris is consistent with the hypothesized deutocerebral innervation of the frontal appendages, reconciling neuroanatomical evidence with external morphology in support of an ancestrally bipartite head and brain for arthropods. We propose that the integration of this bipartite head prior to the acquisition of most segmental characters exclusively in the arthropod trunk may help explain its developmental differentiation.

Extreme multisegmentation in a giant bivalved arthropod from the Cambrian Burgess Shale.

The origin of mandibulate arthropods can be traced back to the Cambrian period to several carapace-bearing arthropod groups, but their morphological diversity is still not well characterized. Here, we describe Balhuticaris voltae, a bivalved arthropod from the 506-million-year-old Burgess Shale (Marble Canyon, British Columbia, Canada). This species has an extremely elongated and multisegmented body bearing ca. 110 pairs of homonomous biramous limbs, the highest number among Cambrian arthropods, and, at 245 mm, it represents one of the largest Cambrian arthropods known. Its unusual carapace resembles an arch; it covers only the frontalmost section of the body but extends ventrally beyond the legs. Balhuticaris had a complex sensory system and was probably an active swimmer thanks to its powerful paddle-shaped exopods and a long and flexible body. Balhuticaris increases the ecological and functional diversity of bivalved arthropods and suggests that cases of gigantism occurred in more arthropod groups than previously recognized.

Integrative PheWAS analysis in risk categorization of major depressive disorder and identifying their associations with genetic variants using a latent topic model approach.

Major depressive disorder (MDD) is the most prevalent mental disorder that constitutes a major public health problem. A tool for predicting the risk of MDD could assist with the early identification of MDD patients and targeted interventions to reduce the risk. We aimed to derive a risk prediction tool that can categorize the risk of MDD as well as discover biologically meaningful genetic variants. Data analyzed were from the fourth and fifth data collections of a longitudinal community-based cohort from Southwest Montreal, Canada, between 2015 and 2018. To account for high dimensional features, we adopted a latent topic model approach to infer a set of topical distributions over those studied predictors that characterize the underlying meta-phenotypes of the MDD cohort. MDD probability derived from 30 MDD meta-phenotypes demonstrated superior prediction accuracy to differentiate MDD cases and controls. Six latent MDD meta-phenotypes we inferred via a latent topic model were highly interpretable. We then explored potential genetic variants that were statistically associated with these MDD meta-phenotypes. The genetic heritability of MDD meta-phenotypes was 0.126 (SE = 0.316), compared to 0.000001 (SE = 0.297) for MDD diagnosis defined by the structured interviews. We discovered a list of significant MDD - related genes and pathways that were missed by MDD diagnosis. Our risk prediction model confers not only accurate MDD risk categorization but also meaningful associations with genetic predispositions that are linked to MDD subtypes. Our findings shed light on future research focusing on these identified genes and pathways for MDD subtypes.

How psychosocial stress profile influences the subsequent occurrence of neuropsychiatric comorbidities: A longitudinal population-based cohort study.

BACKGROUND: The role of psychosocial stressors in psychiatric disorders and executive dysfunction has been reported, separately. The literature has also suggested the involvement of social support and coping strategies in these relationships. However, there is a lack of research conducted to examine the relationships among multiple stressors and neuropsychiatric comorbidities while considering the presence of social support and coping strategies. This study aims to articulate the roles of multiple psychosocial stressors, social support, and coping strategies in the subsequent occurrence of neuropsychiatric comorbidities. METHODS: Data analyzed were from the 6th data collection of a large-scale, longitudinal population-based cohort from Southwest Montreal in Canada. The cumulative effects of multiple stressors were separately examined by a composite score and latent profile analysis. Multinomial logistic regression models were used to test the relationship between cumulative stressors and neuropsychiatric comorbidities. RESULTS: A total of 210 participants were included in the analyses. The LPA identified a 2-class model for psychosocial stressors (low and high) and executive function (executive dysfunction and no executive dysfunction), respectively. There were 11.8% of participants with neuropsychiatric comorbidities. Both the composite stress score (RR = 1.08, 95%CI = 1.01-1.15) and latent stress groups (RR = 3.65, 95%CI = 1.15-11.57) were associated with neuropsychiatric comorbidities after adjusting for social support and coping strategies. The risk of developing neuropsychiatric comorbidities decreased when the level of social support was high (P < 0.05). CONCLUSIONS: Exposures to multiple stressors increased the risk of subsequent neuropsychiatric comorbidities, but the risk can be modified by a higher level of social support.

Endovascular therapy versus microsurgical clipping of unruptured wide-neck aneurysms: a prospective multicenter study with propensity score analysis.

OBJECTIVE: Numerous techniques have been developed to treat wide-neck aneurysms (WNAs), each with different safety and efficacy profiles. Few studies have compared endovascular therapy (EVT) with microsurgery (MS). The authors' objective was to perform a prospective multicenter study of a WNA registry using rigorous outcome assessments and to compare EVT and MS using propensity score analysis (PSA). METHODS: Unruptured, saccular, not previously treated WNAs were included. WNA was defined as an aneurysm with a neck width ≥ 4 mm or a dome-to-neck ratio (DTNR) < 2. The primary outcome was modified Rankin Scale (mRS) score at 1 year after treatment (good outcome was defined as mRS score 0-2), as assessed by blinded research nurses and compared with PSA. Angiographic outcome was assessed using the Raymond scale with core laboratory review (adequate occlusion was defined as Raymond scale score 1-2). RESULTS: The analysis included 224 unruptured aneurysms in the EVT cohort (n = 140) and MS cohort (n = 84). There were no differences in baseline demographic characteristics, such as proportion of patients with good baseline mRS score (94.3% of the EVT cohort vs 94.0% of the MS cohort, p = 0.941). WNA inclusion criteria were similar between cohorts, with the most common being both neck width ≥ 4 mm and DTNR < 2 (50.7% of the EVT cohort vs 50.0% of the MS cohort, p = 0.228). More paraclinoid (32.1% vs 9.5%) and basilar tip (7.1% vs 3.6%) aneurysms were treated with EVT, whereas more middle cerebral artery (13.6% vs 42.9%) and pericallosal (1.4% vs 4.8%) aneurysms were treated with MS (p < 0.001). EVT aneurysms were slightly larger (p = 0.040), and MS aneurysms had a slightly lower mean DTNR (1.4 for the EVT cohort vs 1.3 for the MS cohort, p = 0.010). Within the EVT cohort, 9.3% of patients underwent stand-alone coiling, 17.1% balloon-assisted coiling, 34.3% stent-assisted coiling, 37.1% flow diversion, and 2.1% PulseRider-assisted coiling. Neurological morbidity secondary to a procedural complication was more common in the MS cohort (10.3% vs 1.4%, p = 0.003). One-year mRS scores were assessed for 218 patients (97.3%), and no significantly increased risk of poor clinical outcome was found for the MS cohort (OR 2.17, 95% CI 0.84-5.60, p = 0.110). In an unadjusted direct comparison, more patients in the EVT cohort achieved a good clinical outcome at 1 year (93.4% vs 84.1%, p = 0.048). Final adequate angiographic outcome was superior in the MS cohort (97.6% of the MS cohort vs 86.5% of the EVT cohort, p = 0.007). CONCLUSIONS: Although the treatments for unruptured WNA had similar clinical outcomes according to PSA, there were fewer complications and superior clinical outcome in the EVT cohort and superior angiographic outcomes in the MS cohort according to the unadjusted analysis. These results may be considered when selecting treatment modalities for patients with unruptured WNAs.

Endovascular Therapy Versus Microsurgical Clipping of Ruptured Wide Neck Aneurysms (EVERRUN Registry): a multicenter, prospective propensity score analysis.

OBJECTIVE: Randomized controlled trials have demonstrated the superiority of endovascular therapy (EVT) compared to microsurgery (MS) for ruptured aneurysms suitable for treatment or when therapy is broadly offered to all presenting aneurysms; however, wide neck aneurysms (WNAs) are a challenging subset that require more advanced techniques and warrant further investigation. Herein, the authors sought to investigate a prospective, multicenter WNA registry using rigorous outcome assessments and compare EVT and MS using propensity score analysis (PSA). METHODS: Untreated, ruptured, saccular WNAs were included in the analysis. A WNA was defined as having a neck ≥ 4 mm or a dome/neck ratio (DNR) < 2. The primary outcome was the modified Rankin Scale (mRS) score at 1 year posttreatment, as assessed by blinded research nurses (good outcome: mRS scores 0-2) and compared using PSA. RESULTS: The analysis included 87 ruptured aneurysms: 55 in the EVT cohort and 32 in the MS cohort. Demographics were similar in the two cohorts, including Hunt and Hess grade (p = 0.144) and modified Fisher grade (p = 0.475). WNA type inclusion criteria were similar in the two cohorts, with the most common type having a DNR < 2 (EVT 60.0% vs MS 62.5%). More anterior communicating artery aneurysms (27.3% vs 18.8%) and posterior circulation aneurysms (18.2% vs 0.0%) were treated with EVT, whereas more middle cerebral artery aneurysms were treated with MS (34.4% vs 18.2%, p = 0.025). Within the EVT cohort, 43.6% underwent stand-alone coiling, 50.9% balloon-assisted coiling, 3.6% stent-assisted coiling, and 1.8% flow diversion. The 1-year mRS score was assessed in 81 patients (93.1%), and the primary outcome demonstrated no increased risk for a poor outcome with MS compared to EVT (OR 0.43, 95% CI 0.13-1.45, p = 0.177). The durability of MS was higher, as evidenced by retreatment rates of 12.7% and 0% for EVT and MS, respectively (p = 0.04). CONCLUSIONS: EVT and MS had similar clinical outcomes at 1 year following ruptured WNA treatment. Because of their challenging anatomy, WNAs may represent a population in which EVT's previously demonstrated superiority for ruptured aneurysm treatment is less relevant. Further investigation into the treatment of ruptured WNAs is warranted.

Increased income over time predicts better self-perceived mental health only at a population level but not for individual changes: An analysis of a longitudinal cohort using cross-lagged models.

BACKGROUND: The literature identifies a strong relationship between mental health and income, but there is little research that clarifies the directional association between household income and self-perceived mental health (SPMH) overtime either at between-perso+n or within-person levels. This study investigates whether higher income predicts better SPMH overtime and poor SPMH predicts lower income overtime both at between-person or within-person levels. METHODS: Data analyzed was from the Montreal Southwest Social and Psychiatric Epidemiology Catchment Area study (ZEPSOM), a longitudinal community-based cohort. The baseline survey was conducted in 2007/8 with follow-up every two years. We traced a total of 3464 participants over a period of 8 years. To examine the associations between income and SPMH at both between-person or within-person levels, cross-lagged panel models (CLPMs) and random intercept cross-lagged panel models (RI-CLPMs) were used. Gender and age effects were examined using multiple group analyses. Complete case analyses evaluated the findings' robustness. RESULTS: At between-person levels, higher household income predicted higher SPMH, but not vice versa. These associations were stronger among men and older adults. At within-person levels, higher income did not predict higher SPMH. No significant gender- or age- group differences were observed. Complete case analyses supported the findings. LIMITATIONS: Loss to follow-up may affect the generalizability of the research findings. CONCLUSIONS: This study suggests that higher household income predicts higher SPMH at between-person levels. Policy and programs aiming at promoting mental health should focus on low-income individuals, especially men and older adults.

Symbiosis in the Cambrian: enteropneust tubes from the Burgess Shale co-inhabited by commensal polychaetes.

The in situ preservation of animal behaviour in the fossil record is exceedingly rare, but can lead to unique macroecological and macroevolutionary insights, especially regarding early representatives of major animal clades. We describe a new complex ecological relationship from the middle Cambrian Burgess Shale (Raymond Quarry, Canada). More than 30 organic tubes were recorded with multiple enteropneust and polychaete worms preserved within them. Based on the tubicolous nature of fossil enteropneusts, we suggest that they were the tube builders while the co-preserved polychaetes were commensals. These findings mark, to our knowledge, the first record of commensalism within Annelida and Hemichordata in the entire fossil record. The finding of multiple enteropneusts sharing common tubes suggests that either the tubes represent reproductive structures built by larger adults, and the enteropneusts commonly preserved within are juveniles, or these enteropneusts were living as a pseudo-colony without obligate attachment to each other, and the tube was built collaboratively. While neither hypothesis can be ruled out, gregarious behaviour was clearly an early trait of both hemichordates and annelids. Further, commensal symbioses in the Cambrian may be more common than currently recognized.

Fish without Tail Fins-Exploring the Function of Tail Morphology of the First Vertebrates.

We use a series of hydrodynamic experiments on abstracted models to explore whether primitive vertebrates may have swum under various conditions without a clearly-differentiated tail fin. Cambrian vertebrates had post-anal stubby tails, some had single dorsal and ventral fins, but none had yet evolved a clearly differentiated caudal fin typical of post-Cambrian fishes, and must have relied on their long and flexible laterally-compressed bodies for locomotion, i.e., by bending their bodies side-to-side in order to propagate waves from head to tail. We approach this problem experimentally based on an abstracted model of Metaspriggina walcotti from the 506-million-year old Burgess Shale by using oscillating thin flexible plates while varying the tail fin geometry from rectangular to uniform, and finally to a no tail-fin condition. Despite a missing tail fin, this study supports the observation that the abstracted Metaspriggina model can generate a strong propulsive force in cruise conditions, both away from, and near the sea bed (in ground effect). However, when the abstracted Metaspriggina model moves in ground effect, a weaker performance is observed, indicating that Metaspriggina may not necessarily have been optimized for swimming near the sea bed. When considering acceleration from rest, we find that the Metaspriggina model's performance is not significantly different from other morphological models (abstracted truncate tail and abstracted heterocercal tail). Statistical analysis shows that morphological parameters, swimming modes, and ground effect all play significant roles in thrust performance. While the exact relationships of Cambrian vertebrates are still debated, as agnathans, they share some general characteristics with modern cyclostomes, in particular an elongate body akin to lampreys. Lampreys, as anguilliform swimmers, are considered to be some of the most efficient swimmers using a particular type of suction thrust induced by the traveling body wave as it travels from head to tail. Our current experiments suggest that Metaspriggina's ability in acceleration from rest, through possibly a similar type of suction thrust, which is defined as the ability to generate low pressure on upstream facing sections of the body, might have evolved early in response to increasing predator pressure during the Cambrian Explosion.

Relative 'greenness' and not availability of public open space buffers stressful life events and longitudinal trajectories of psychological distress.

Despite evidence of associations between urban green space exposure and mental health, explanatory mechanisms and the role of green space qualities remain unclear. This prospective cohort study (n = 929) examined the distinct relationships of residential public open space (POS) availability and 'greenness' with four-year trajectories of psychological distress in Montreal, Canada. Stress-buffering and main effect mechanisms were tested under the respective hypotheses that POS exposures 1) attenuate the impact of stressful events on psychological distress and 2) protect against psychological distress independently of exposure to stressful events. Results from growth mixture models indicate that residing among 'greener' POS protects against rising distress through both mechanisms. Conversely, POS availability was not associated with trajectories of distress when holding greenness constant. Findings reinforce the need to consider the quality as well as quantity of public open space in urban environments.

Impact of parental socioeconomic status on offspring's mental health: protocol for a longitudinal community-based study.

INTRODUCTION: Socioeconomic status (SES) affects physical and mental health and cognitive functioning. The association between SES changes (SES mobility) and health has ethical and political implications in that the pernicious effects of inequality and the differential impact on social classes of economic and social policies. There is a lack of research conducted to explore the intergenerational transmission of parental SES changes on the offspring's mental health and cognitive functioning. We aim to fill this gap and identify roles of parental SES changes in offspring's mental health and cognitive outcomes. METHODS AND ANALYSIS: This study will be based on a longitudinal cohort from the most populous municipality in the Canadian province of Quebec. Participants and their biological offspring will be invited to this study. For those with informed consent, we will collect their information on mental health, psychiatric disorders, cognitive functioning and early life experiences for offspring. Latent class growth analysis will be used to identify parental SES mobility groups. Multivariate regression analyses will be used to explore the roles of early life stress, parental SES mobility and their interactions in psychiatric disorders and cognitive functioning. Subgroup analyses (males and females) are also planned. ETHICS AND DISSEMINATION: This study has been given ethical approval by the Research Ethics Board of the Douglas Mental Health University Institute (IUSMD-18/17). Each participant will provide informed consent on participation. We will disseminate research findings through publication in peer-reviewed academic journals and presentations at conferences. Lay summaries of major research findings will also be shared annually with our partners in the health system and community agencies located in the catchment area.

Intracerebral Hemorrhage Volume Reduction and Timing of Intervention Versus Functional Benefit and Survival in the MISTIE III and STICH Trials.

BACKGROUND: The extent of intracerebral hemorrhage (ICH) removal conferred survival and functional benefits in the minimally invasive surgery with thrombolysis in intracerebral hemorrhage evacuation (MISTIE) III trial. It is unclear whether this similarly impacts outcome with craniotomy (open surgery) or whether timing from ictus to intervention influences outcome with either procedure. OBJECTIVE: To compare volume evacuation and timing of surgery in relation to outcomes in the MISTIE III and STICH (Surgical Trial in Intracerebral Hemorrhage) trials. METHODS: Postoperative scans were performed in STICH II, but not in STICH I; therefore, surgical MISTIE III cases with lobar hemorrhages (n = 84) were compared to STICH II all lobar cases (n = 259) for volumetric analyses. All MISTIE III surgical patients (n = 240) were compared to both STICH I and II (n = 722) surgical patients for timing analyses. These were investigated using cubic spline modeling and multivariate risk adjustment. RESULTS: End-of-treatment ICH volume ≤28.8 mL in MISTIE III and ≤30.0 mL in STICH II had increased probability of modified Rankin Scale (mRS) 0 to 3 at 180 d (P = .01 and P = .003, respectively). The effect in the MISTIE cohort remained significant after multivariate risk adjustments. Earlier surgery within 62 h of ictus had a lower probability of achieving an mRS 0 to 3 at 180 d with STICH I and II (P = .0004), but not with MISTIE III. This remained significant with multivariate risk adjustments. There was no impact of timing until intervention on mortality up to 47 h with either procedure. CONCLUSION: Thresholds of ICH removal influenced outcome with both procedures to a similar extent. There was a similar likelihood of achieving a good outcome with both procedures within a broad therapeutic time window.

Thrombolysis for Evacuation of Intracerebral and Intraventricular Hemorrhage: A Guide to Surgical Protocols With Practical Lessons Learned From the MISTIE and CLEAR Trials.

BACKGROUND: Minimally Invasive Surgery Plus Recombinant Tissue Plasminogen Activator for Intracerebral Hemorrhage Evacuation (MISTIE) procedure was recently tested in a large phase III randomized trial showing a significant probability of functional benefit in those cases that reached the goal hematoma evacuation of ≤15 mL residual (or ≥70% removal). Benefit of thrombolysis was also identified in cases with large intraventricular hemorrhage, and achieving at least 85% volume reduction in the Evaluating Accelerated Resolution of Intraventricular Hemorrhage (CLEAR) III trial. OBJECTIVE: To protocolize steps in the MISTIE and CLEAR procedures in order to maximize hematoma evacuation and minimize complications. METHODS: We articulate data-driven lessons and expert opinions surrounding the factors of patient selection, catheter placement, and dosing, which impacted safety and surgical performance in the MISTIE and CLEAR trials. RESULTS: Modifiable factors to maximize evacuation efficiency include optimizing catheter placement and pursuing aggressive dosing to achieve treatment goals, while strictly adhering to the safety steps as articulated in the respective trials. Prognostic factors that are viewed as nonmodifiable include greater initial intracerebral hemorrhage volume with irregular shape, smaller intraventricular bleeds, and the uncommon but consequential development of new bleeding during the dosing period despite strict protocol adherence. CONCLUSIONS: Surgeon education in this tutorial is aimed at maximizing the benefit of the MISTIE and CLEAR procedures by reviewing case selection, safety steps, treatment objectives, and technical nuances. Key lessons include stability imaging, etiology screening, and technical adherence to the protocol in order to achieve defined thresholds of evacuation.