A middle Cambrian arthropod with chelicerae and proto-book gills.

The chelicerates are a ubiquitous and speciose group of animals that has a considerable ecological effect on modern terrestrial ecosystems-notably as predators of insects and also, for instance, as decomposers1. The fossil record shows that chelicerates diversified early in the marine ecosystems of the Palaeozoic era, by at least the Ordovician period2. However, the timing of chelicerate origins and the type of body plan that characterized the earliest members of this group have remained controversial. Although megacheirans3-5 have previously been interpreted as chelicerate-like, and habeliidans6 (including Sanctacaris7,8) have been suggested to belong to their immediate stem lineage, evidence for the specialized feeding appendages (chelicerae) that are diagnostic of the chelicerates has been lacking. Here we use exceptionally well-preserved and abundant fossil material from the middle Cambrian Burgess Shale (Marble Canyon, British Columbia, Canada) to show that Mollisonia plenovenatrix sp. nov. possessed robust but short chelicerae that were placed very anteriorly, between the eyes. This suggests that chelicerae evolved a specialized feeding function early on, possibly as a modification of short antennules. The head also encompasses a pair of large compound eyes, followed by three pairs of long, uniramous walking legs and three pairs of stout, gnathobasic masticatory appendages; this configuration links habeliidans with euchelicerates ('true' chelicerates, excluding the sea spiders). The trunk ends in a four-segmented pygidium and bears eleven pairs of identical limbs, each of which is composed of three broad lamellate exopod flaps, and endopods are either reduced or absent. These overlapping exopod flaps resemble euchelicerate book gills, although they lack the diagnostic operculum9. In addition, the eyes of M. plenovenatrix were innervated by three optic neuropils, which strengthens the view that a complex malacostracan-like visual system10,11 might have been plesiomorphic for all crown euarthropods. These fossils thus show that chelicerates arose alongside mandibulates12 as benthic micropredators, at the heart of the Cambrian explosion.

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.

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.

Burgess Shale fossils illustrate the origin of the mandibulate body plan.

Retracing the evolutionary history of arthropods has been one of the greatest challenges in biology. During the past decade, phylogenetic analyses of morphological and molecular data have coalesced towards the conclusion that Mandibulata, the most diverse and abundant group of animals, is a distinct clade from Chelicerata, in that its members possess post-oral head appendages specialized for food processing, notably the mandible. The origin of the mandibulate body plan, however, which encompasses myriapods, crustaceans and hexapods, has remained poorly documented. Here we show that Tokummia katalepsis gen. et sp. nov., a large bivalved arthropod from the 508 million-year-old Marble Canyon fossil deposit (Burgess Shale, British Columbia), has unequivocal mandibulate synapomorphies, including mandibles and maxillipeds, as well as characters typically found in crustaceans, such as enditic, subdivided basipods and ring-shaped trunk segments. Tokummia and its closest relative, Branchiocaris (in Protocarididae, emended), also have an anteriormost structure housing a probable bilobed organ, which could support the appendicular origin of the labrum. Protocaridids are retrieved with Canadaspis and Odaraia (in Hymenocarina, emended) as part of an expanded mandibulate clade, refuting the idea that these problematic bivalved taxa, as well as other related forms, are representatives of the basalmost euarthropods. Hymenocarines now illustrate that the subdivision of the basipod and the presence of proximal endites are likely to have been ancestral conditions critical for the evolution of coxal and pre-coxal features in mandibulates. The presence of crustaceomorph traits in the Cambrian larvae of various clades basal to Mandibulata is reinterpreted as evidence for the existence of distinct ontogenetic niches among stem arthropods. Larvae would therefore have constituted an important source of morphological novelty during the Cambrian period, and, through heterochronic processes, may have contributed to the rapid acquisition of crown-group characters and thus to greater evolutionary rates during the early radiation of euarthropods.

Hyoliths are Palaeozoic lophophorates.

Hyoliths are abundant and globally distributed 'shelly' fossils that appear early in the Cambrian period and can be found throughout the 280 million year span of Palaeozoic strata. The ecological and evolutionary importance of this group has remained unresolved, largely because of their poorly constrained soft anatomy and idiosyncratic scleritome, which comprises an operculum, a conical shell and, in some taxa, a pair of lateral spines (helens). Since their first description over 175 years ago, hyoliths have most often been regarded as incertae sedis, related to molluscs or assigned to their own phylum. Here we examine over 1,500 specimens of the mid-Cambrian hyolith Haplophrentis from the Burgess Shale and Spence Shale Lagerstätten. We reconstruct Haplophrentis as a semi-sessile, epibenthic suspension feeder that could use its helens to elevate its tubular body above the sea floor. Exceptionally preserved soft tissues include an extendable, gullwing-shaped, tentacle-bearing organ surrounding a central mouth, which we interpret as a lophophore, and a U-shaped digestive tract ending in a dorsolateral anus. Together with opposing bilateral sclerites and a deep ventral visceral cavity, these features indicate an affinity with the lophophorates (brachiopods, phoronids and tommotiids), substantially increasing the morphological disparity of this prominent group.

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.

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.

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.

Hallucigenia's head and the pharyngeal armature of early ecdysozoans.

The molecularly defined clade Ecdysozoa comprises the panarthropods (Euarthropoda, Onychophora and Tardigrada) and the cycloneuralian worms (Nematoda, Nematomorpha, Priapulida, Loricifera and Kinorhyncha). These disparate phyla are united by their means of moulting, but otherwise share few morphological characters--none of which has a meaningful fossilization potential. As such, the early evolutionary history of the group as a whole is largely uncharted. Here we redescribe the 508-million-year-old stem-group onychophoran Hallucigenia sparsa from the mid-Cambrian Burgess Shale. We document an elongate head with a pair of simple eyes, a terminal buccal chamber containing a radial array of sclerotized elements, and a differentiated foregut that is lined with acicular teeth. The radial elements and pharyngeal teeth resemble the sclerotized circumoral elements and pharyngeal teeth expressed in tardigrades, stem-group euarthropods and cycloneuralian worms. Phylogenetic results indicate that equivalent structures characterized the ancestral panarthropod and, seemingly, the ancestral ecdysozoan, demonstrating the deep homology of panarthropod and cycloneuralian mouthparts, and providing an anatomical synapomorphy for the ecdysozoan supergroup.

Efficacy and safety of minimally invasive surgery with thrombolysis in intracerebral haemorrhage evacuation (MISTIE III): a randomised, controlled, open-label, blinded endpoint phase 3 trial.

BACKGROUND: Acute stroke due to supratentorial intracerebral haemorrhage is associated with high morbidity and mortality. Open craniotomy haematoma evacuation has not been found to have any benefit in large randomised trials. We assessed whether minimally invasive catheter evacuation followed by thrombolysis (MISTIE), with the aim of decreasing clot size to 15 mL or less, would improve functional outcome in patients with intracerebral haemorrhage. METHODS: MISTIE III was an open-label, blinded endpoint, phase 3 trial done at 78 hospitals in the USA, Canada, Europe, Australia, and Asia. We enrolled patients aged 18 years or older with spontaneous, non-traumatic, supratentorial intracerebral haemorrhage of 30 mL or more. We used a computer-generated number sequence with a block size of four or six to centrally randomise patients to image-guided MISTIE treatment (1·0 mg alteplase every 8 h for up to nine doses) or standard medical care. Primary outcome was good functional outcome, defined as the proportion of patients who achieved a modified Rankin Scale (mRS) score of 0-3 at 365 days, adjusted for group differences in prespecified baseline covariates (stability intracerebral haemorrhage size, age, Glasgow Coma Scale, stability intraventricular haemorrhage size, and clot location). Analysis of the primary efficacy outcome was done in the modified intention-to-treat (mITT) population, which included all eligible, randomly assigned patients who were exposed to treatment. All randomly assigned patients were included in the safety analysis. This study is registered with ClinicalTrials.gov, number NCT01827046. FINDINGS: Between Dec 30, 2013, and Aug 15, 2017, 506 patients were randomly allocated: 255 (50%) to the MISTIE group and 251 (50%) to standard medical care. 499 patients (n=250 in the MISTIE group; n=249 in the standard medical care group) received treatment and were included in the mITT analysis set. The mITT primary adjusted efficacy analysis estimated that 45% of patients in the MISTIE group and 41% patients in the standard medical care group had achieved an mRS score of 0-3 at 365 days (adjusted risk difference 4% [95% CI -4 to 12]; p=0·33). Sensitivity analyses of 365-day mRS using generalised ordered logistic regression models adjusted for baseline variables showed that the estimated odds ratios comparing MISTIE with standard medical care for mRS scores higher than 5 versus 5 or less, higher than 4 versus 4 or less, higher than 3 versus 3 or less, and higher than 2 versus 2 or less were 0·60 (p=0·03), 0·84 (p=0·42), 0·87 (p=0·49), and 0·82 (p=0·44), respectively. At 7 days, two (1%) of 255 patients in the MISTIE group and ten (4%) of 251 patients in the standard medical care group had died (p=0·02) and at 30 days, 24 (9%) patients in the MISTIE group and 37 (15%) patients in the standard medical care group had died (p=0·07). The number of patients with symptomatic bleeding and brain bacterial infections was similar between the MISTIE and standard medical care groups (six [2%] of 255 patients vs three [1%] of 251 patients; p=0·33 for symptomatic bleeding; two [1%] of 255 patients vs 0 [0%] of 251 patients; p=0·16 for brain bacterial infections). At 30 days, 76 (30%) of 255 patients in the MISTIE group and 84 (33%) of 251 patients in the standard medical care group had one or more serious adverse event, and the difference in number of serious adverse events between the groups was statistically significant (p=0·012). INTERPRETATION: For moderate to large intracerebral haemorrhage, MISTIE did not improve the proportion of patients who achieved a good response 365 days after intracerebral haemorrhage. The procedure was safely adopted by our sample of surgeons. FUNDING: National Institute of Neurological Disorders and Stroke and Genentech.

A primitive fish from the Cambrian of North America.

Knowledge of the early evolution of fish largely depends on soft-bodied material from the Lower (Series 2) Cambrian period of South China. Owing to the rarity of some of these forms and a general lack of comparative material from other deposits, interpretations of various features remain controversial, as do their wider relationships amongst post-Cambrian early un-skeletonized jawless vertebrates. Here we redescribe Metaspriggina on the basis of new material from the Burgess Shale and exceptionally preserved material collected near Marble Canyon, British Columbia, and three other Cambrian Burgess Shale-type deposits from Laurentia. This primitive fish displays unambiguous vertebrate features: a notochord, a pair of prominent camera-type eyes, paired nasal sacs, possible cranium and arcualia, W-shaped myomeres, and a post-anal tail. A striking feature is the branchial area with an array of bipartite bars. Apart from the anterior-most bar, which appears to be slightly thicker, each is associated with externally located gills, possibly housed in pouches. Phylogenetic analysis places Metaspriggina as a basal vertebrate, apparently close to the Chengjiang taxa Haikouichthys and Myllokunmingia, demonstrating also that this primitive group of fish was cosmopolitan during Lower-Middle Cambrian times (Series 2-3). However, the arrangement of the branchial region in Metaspriggina has wider implications for reconstructing the morphology of the primitive vertebrate. Each bipartite bar is identified as being respectively equivalent to an epibranchial and ceratobranchial. This configuration suggests that a bipartite arrangement is primitive and reinforces the view that the branchial basket of lampreys is probably derived. Other features of Metaspriggina, including the external position of the gills and possible absence of a gill opposite the more robust anterior-most bar, are characteristic of gnathostomes and so may be primitive within vertebrates.

Baseline income, follow-up income, income mobility and their roles in mental disorders: a longitudinal intra-generational community-based study.

BACKGROUND: Although a number of studies have found that income mobility associated with an elevated risk of mental disorders, existing research does not provide sufficient evidence of how exactly individuals' experience of income mobility per se affects their risk of mental health outcomes. This present study aimed to explore roles of baseline income, follow-up income, and income mobility in the development of mental disorders using an intra-generational, longitudinal follow-up study. METHODS: We used data from the Montreal South-West Longitudinal Catchment Area Study. A total of 1117 participants with complete information both on income and past 12-month diagnoses of mental disorders were selected for this study. Diagonal Reference Models were used to simultaneously examine roles of income at baseline, income at follow-up, and income mobility in mental disorders during a 4-year follow-up. RESULTS: Both baseline and follow-up income were important predictors for any mental disorder and major depression among males and females. Those with low income had a higher risk of any mental disorders and major depression. No evidence was found to support an association between income mobility (neither downwards nor upwards) and mental disorders. Marital status was uniquely associated with any mental disorder among males. Having a pre-existing diagnosis of any mental disorder at origin was associated with any mental disorder and major depression at the end of the 4-year follow-up. CONCLUSIONS: This study first simultaneously examined roles of income at baseline, at follow-up, and mobility in mental disorders among a large-scale intra-generational community-based study. This present study provides additional evidence on how income is associated with an individuals' likelihood of mental disorders.

Soft-Bodied Fossils Are Not Simply Rotten Carcasses - Toward a Holistic Understanding of Exceptional Fossil Preservation: Exceptional Fossil Preservation Is Complex and Involves the Interplay of Numerous Biological and Geological Processes.

Exceptionally preserved fossils are the product of complex interplays of biological and geological processes including burial, autolysis and microbial decay, authigenic mineralization, diagenesis, metamorphism, and finally weathering and exhumation. Determining which tissues are preserved and how biases affect their preservation pathways is important for interpreting fossils in phylogenetic, ecological, and evolutionary frameworks. Although laboratory decay experiments reveal important aspects of fossilization, applying the results directly to the interpretation of exceptionally preserved fossils may overlook the impact of other key processes that remove or preserve morphological information. Investigations of fossils preserving non-biomineralized tissues suggest that certain structures that are decay resistant (e.g., the notochord) are rarely preserved (even where carbonaceous components survive), and decay-prone structures (e.g., nervous systems) can fossilize, albeit rarely. As we review here, decay resistance is an imperfect indicator of fossilization potential, and a suite of biological and geological processes account for the features preserved in exceptional fossils.

Transitional Employment and Psychological Distress: a Longitudinal Study.

Although it has been established that employed status is generally associated with better mental health than unemployed status, the psychological mechanisms that underlie the longitudinal association between employment status and psychological distress remain to be understood. Initial mental health, lower coping skills and social support, and more stressful events could potentially preselect certain vulnerable individuals to be at higher risk for unemployment or employment instability. The aim of this study was to examine the longitudinal association between employment status (including transitional employment status) and psychological distress, controlling for the effect of initial psychological distress, coping skills, social support, and stressful events. In 2009, residents from the epidemiological catchment area of south-west Montréal responded to a randomized household survey for adults. Follow-up surveys were conducted in 2011 and 2013 (n = 1168). Psychological distress was measured using the K-10 scale. Employment status was not significantly associated with psychological distress over time, however there were significant differences between the groups with the continually employed reporting the lowest average levels of psychological distress over time. Controlling for coping skills, social support, stressful events and initial psychological distress changed the strengths of the association between transitional employment status and psychological distress at follow-up. A significant longitudinal association between continual unemployment and psychological distress was observed. Initial psychological distress was significantly associated with becoming unemployed. Results suggest initial psychological distress as a risk factor for becoming unemployed and that the negative psychological implications of employment transitions can be significantly reduced when conditions for coping are optimized.

Tubicolous enteropneusts from the Cambrian period.

Hemichordates are a marine group that, apart from one monospecific pelagic larval form, are represented by the vermiform enteropneusts and minute colonial tube-dwelling pterobranchs. Together with echinoderms, they comprise the clade Ambulacraria. Despite their restricted diversity, hemichordates provide important insights into early deuterostome evolution, notably because of their pharyngeal gill slits. Hemichordate phylogeny has long remained problematic, not least because the nature of any transitional form that might serve to link the anatomically disparate enteropneusts and pterobranchs is conjectural. Hence, inter-relationships have also remained controversial. For example, pterobranchs have sometimes been compared to ancestral echinoderms. Molecular data identify enteropneusts as paraphyletic, and harrimaniids as the sister group of pterobranchs. Recent molecular phylogenies suggest that enteropneusts are probably basal within hemichordates, contrary to previous views, but otherwise provide little guidance as to the nature of the primitive hemichordate. In addition, the hemichordate fossil record is almost entirely restricted to peridermal skeletons of pterobranchs, notably graptolites. Owing to their low preservational potentials, fossil enteropneusts are exceedingly rare, and throw no light on either hemichordate phylogeny or the proposed harrimaniid-pterobranch transition. Here we describe an enteropneust, Spartobranchus tenuis (Walcott, 1911), from the Middle Cambrian-period (Series 3, Stage 5) Burgess Shale. It is remarkably similar to the extant harrimaniids, but differs from all known enteropneusts in that it is associated with a fibrous tube that is sometimes branched. We suggest that this is the precursor of the pterobranch periderm, and supports the hypothesis that pterobranchs are miniaturized and derived from an enteropneust-like worm. It also shows that the periderm was acquired before size reduction and acquisition of feeding tentacles, and that coloniality emerged through aggregation of individuals, perhaps similar to the Cambrian rhabdopleurid Fasciculitubus. The presence of both enteropneusts and pterobranchs in Middle Cambrian strata, suggests that hemichordates originated at the onset of the Cambrian explosion.

Predictors of Quality of Life in Montreal, Canada: A Longitudinal Study.

This study sought to assess factors associated with quality of life (QoL), and predictive of improvements in QoL over time, in a population-based cohort study. A 4-year longitudinal survey was administered to 2433 individuals at the study baseline; of these, 1828 individuals participated in Wave 2, and 1303 participated in Wave 3. QoL was measured by the Satisfaction with Life Domains Scale. Thirty-two variables were correlated with baseline QoL and together explained 58.2% of the variance. Eleven variables were independent predictors of improvement in QoL over time. Among these variables, social support and stress/coping showed the strongest association with QoL, and neighbourhood characteristics had an additional influence. Multidimensional modelling of a broad spectrum of the factors related to QoL enabled situating mental health and well-being in an ecological system with attendant implications for public health and social policy intervention to facilitate improvement of QoL in the population.

Correction to: Mandibulate convergence in an armoured Cambrian stem chelicerate.

The original article [1] had 4 paragraphs which contained erroneous information. In this correction article the correct and incorrect information is shown.

Thrombolytic removal of intraventricular haemorrhage in treatment of severe stroke: results of the randomised, multicentre, multiregion, placebo-controlled CLEAR III trial.

BACKGROUND: Intraventricular haemorrhage is a subtype of intracerebral haemorrhage, with 50% mortality and serious disability for survivors. We aimed to test whether attempting to remove intraventricular haemorrhage with alteplase versus saline irrigation improved functional outcome. METHODS: In this randomised, double-blinded, placebo-controlled, multiregional trial (CLEAR III), participants with a routinely placed extraventricular drain, in the intensive care unit with stable, non-traumatic intracerebral haemorrhage volume less than 30 mL, intraventricular haemorrhage obstructing the 3rd or 4th ventricles, and no underlying pathology were adaptively randomly assigned (1:1), via a web-based system to receive up to 12 doses, 8 h apart of 1 mg of alteplase or 0·9% saline via the extraventricular drain. The treating physician, clinical research staff, and participants were masked to treatment assignment. CT scans were obtained every 24 h throughout dosing. The primary efficacy outcome was good functional outcome, defined as a modified Rankin Scale score (mRS) of 3 or less at 180 days per central adjudication by blinded evaluators. This study is registered with ClinicalTrials.gov, NCT00784134. FINDINGS: Between Sept 18, 2009, and Jan 13, 2015, 500 patients were randomised: 249 to the alteplase group and 251 to the saline group. 180-day follow-up data were available for analysis from 246 of 249 participants in the alteplase group and 245 of 251 participants in the placebo group. The primary efficacy outcome was similar in each group (good outcome in alteplase group 48% vs saline 45%; risk ratio [RR] 1·06 [95% CI 0·88-1·28; p=0·554]). A difference of 3·5% (RR 1·08 [95% CI 0·90-1·29], p=0·420) was found after adjustment for intraventricular haemorrhage size and thalamic intracerebral haemorrhage. At 180 days, the treatment group had lower case fatality (46 [18%] vs saline 73 [29%], hazard ratio 0·60 [95% CI 0·41-0·86], p=0·006), but a greater proportion with mRS 5 (42 [17%] vs 21 [9%]; RR 1·99 [95% CI 1·22-3·26], p=0·007). Ventriculitis (17 [7%] alteplase vs 31 [12%] saline; RR 0·55 [95% CI 0·31-0·97], p=0·048) and serious adverse events (114 [46%] alteplase vs 151 [60%] saline; RR 0·76 [95% CI 0·64-0·90], p=0·002) were less frequent with alteplase treatment. Symptomatic bleeding (six [2%] in the alteplase group vs five [2%] in the saline group; RR 1·21 [95% CI 0·37-3·91], p=0·771) was similar. INTERPRETATION: In patients with intraventricular haemorrhage and a routine extraventricular drain, irrigation with alteplase did not substantially improve functional outcomes at the mRS 3 cutoff compared with irrigation with saline. Protocol-based use of alteplase with extraventricular drain seems safe. Future investigation is needed to determine whether a greater frequency of complete intraventricular haemorrhage removal via alteplase produces gains in functional status. FUNDING: National Institute of Neurological Disorders and Stroke.

Patterns of Health Care Service Utilization by Individuals with Mental Health Problems: a Predictive Cluster Analysis.

This study aimed at identifying and characterizing clusters of mental health service users based on various characteristics in a sample of individuals with mental health problems. Data were collected in the epidemiological catchment area of South-West Montreal, Quebec in 2011 and 2014. Among the 746 participants who reported experiencing a mental health problem (high psychological distress and/or a mental disorder), 29% had used mental health services. A Two-Step cluster analysis was carried out to generate participant profiles based on their visit to mental health professional. Four clusters were identified: 1) young males with high quality of life and social support and who were less likely to have mental health problems and to utilize mental health services; 2) older females living with a partner and having a family doctor who were less likely to have mental health problems and to utilize mental health services; 3) single females with generalized anxiety disorder and somatic illness who were more likely to utilize mental health services, and 4) depressed females with high psychological distress, low quality of life and social support who were likely to utilize mental health services. The results reinforce the importance to develop programs that target the specific needs of subgroups of people experiencing mental health problems, given their considerable heterogeneity.

Mandibulate convergence in an armoured Cambrian stem chelicerate.

BACKGROUND: Chelicerata represents a vast clade of mostly predatory arthropods united by a distinctive body plan throughout the Phanerozoic. Their origins, however, with respect to both their ancestral morphological features and their related ecologies, are still poorly understood. In particular, it remains unclear whether their major diagnostic characters were acquired early on, and their anatomical organization rapidly constrained, or if they emerged from a stem lineage encompassing an array of structural variations, based on a more labile "panchelicerate" body plan. RESULTS: In this study, we reinvestigated the problematic middle Cambrian arthropod Habelia optata Walcott from the Burgess Shale, and found that it was a close relative of Sanctacaris uncata Briggs and Collins (in Habeliida, ord. nov.), both retrieved in our Bayesian phylogeny as stem chelicerates. Habelia possesses an exoskeleton covered in numerous spines and a bipartite telson as long as the rest of the body. Segments are arranged into three tagmata. The prosoma includes a reduced appendage possibly precursor to the chelicera, raptorial endopods connected to five pairs of outstandingly large and overlapping gnathobasic basipods, antennule-like exopods seemingly dissociated from the main limb axis, and, posteriorly, a pair of appendages morphologically similar to thoracic ones. While the head configuration of habeliidans anchors a seven-segmented prosoma as the chelicerate ground pattern, the peculiar size and arrangement of gnathobases and the presence of sensory/tactile appendages also point to an early convergence with the masticatory head of mandibulates. CONCLUSIONS: Although habeliidans illustrate the early appearance of some diagnostic chelicerate features in the evolution of euarthropods, the unique convergence of their cephalons with mandibulate anatomies suggests that these traits retained an unusual variability in these taxa. The common involvement of strong gnathal appendages across non-megacheirans Cambrian taxa also illustrates that the specialization of the head as the dedicated food-processing tagma was critical to the emergence of both lineages of extant euarthropods-Chelicerata and Mandibulata-and implies that this diversification was facilitated by the expansion of durophagous niches.