Systematic review of early warning signs of relapse and behavioural antecedents of symptom worsening in people living with schizophrenia spectrum disorders.

BACKGROUND: Identification of the early warning signs (EWS) of relapse is key to relapse prevention in schizophrenia spectrum disorders, however, limitations to their precision have been reported. Substantial methodological innovations have recently been applied to the prediction of psychotic relapse and to individual psychotic symptoms. However, there has been no systematic review that has integrated findings across these two related outcomes and no systematic review of EWS of relapse for a decade. METHOD: We conducted a systematic review of EWS of psychotic relapse and the behavioural antecedents of worsening psychotic symptoms. Traditional EWS and ecological momentary assessment/intervention studies were included. We completed meta-analyses of the pooled sensitivity and specificity of EWS in predicting relapse, and for the prediction of relapse from individual symptoms. RESULTS: Seventy two studies were identified including 6903 participants. Sleep, mood, and suspiciousness, emerged as predictors of worsening symptoms. Pooled sensitivity and specificity of EWS in predicting psychotic relapse was 71% and 64% (AUC value = 0.72). There was a large pooled-effect size for the model predicting relapse from individual symptom which did not reach statistical significance (d = 0.81, 95%CIs = -0.01, 1.63). CONCLUSIONS: Important methodological advancements in the prediction of psychotic relapse in schizophrenia spectrum disorders are evident with improvements in the precision of prediction. Further efforts are required to translate these advances into effective clinical innovations.

Nearby night lighting, rather than sky glow, is associated with habitat selection by a top predator in human-dominated landscapes.

Artificial light at night (ALAN) is increasing in extent and intensity across the globe. It has been shown to interfere with animal sensory systems, orientation and distribution, with the potential to cause significant ecological impacts. We analysed the locations of 102 mountain lions (Puma concolor) in a light-polluted region in California. We modelled their distribution relative to environmental and human-disturbance variables, including upward radiance (nearby lights), zenith brightness (sky glow) and natural illumination from moonlight. We found that mountain lion probability of presence was highly related to upward radiance, that is, related to lights within approximately 500 m. Despite a general pattern of avoidance of locations with high upward radiance, there were large differences in degree of avoidance among individuals. The amount of light from artificial sky glow was not influential when included together with upward radiance in the models, and illumination from moonlight was not influential at all. Our results suggest that changes in visibility associated with lunar cycles and sky glow are less important for mountain lions in their selection of light landscapes than avoiding potential interactions with humans represented by the presence of nearby lights on the ground. This article is part of the theme issue 'Light pollution in complex ecological systems'.

Feasibility of Non-Gated Dynamic Fetal Cardiac MRI for Identification of Fetal Cardiovascular Anatomy.

INTRODUCTION: The aim of this study was to evaluate the feasibility of identifying the fetal cardiac and thoracic vascular structures with non-gated dynamic balanced steady-state free precession (SSFP) MRI sequences. METHODS: We retrospectively assessed the visibility of cardiovascular anatomy in 60 fetuses without suspicion of congenital heart defect. Non-gated dynamic balanced SSFP sequences were acquired in three anatomic planes of the fetal thorax. The images were analyzed following a segmental approach in consensus reading by an experienced pediatric cardiologist and radiologist. An imaging score was defined by giving one point to each visualized structure, yielding a maximum score of 21 points. Image quality was rated from 0 (poor) to 2 (excellent). The influence of gestational age (GA), field strength, placenta position, and maternal panniculus on image quality and imaging score were tested. RESULTS: 30 scans were performed at 1.5T, 30 at 3T. Heart position, atria, and ventricles could be seen in all 60 fetuses. Basic diagnosis (>12 points) was achieved in 54 cases. The mean imaging score was 16.8+/-3.8. Maternal panniculus (r = -0.3; p = 0.015) and GA (r = 0.6; p < 0.001) correlated with imaging score. Field strength influenced image quality, with 1.5T being better than 3T images (p = 0.012). Imaging score or quality was independent of placenta position. CONCLUSION: Fetal cardiac MRI with non-gated SSFP sequences enables recognition of basic cardiovascular anatomy.

Animal board invited review: Grassland-based livestock farming and biodiversity.

Grasslands dominate land cover nationally and globally, and their composition, structure and habitat value are strongly influenced by the actions of domestic and wild grazing animals that feed on them. Different pastures are characterised by varying opportunities for selective feeding by livestock; agronomically improved, sown swards generally consist of a limited range of plant species whereas longer-term leys and semi-natural grasslands are characterised by a more diverse mixture of plants. In the case of botanically diverse permanent pastures/grazing lands, the dietary preferences of different grazers have a more pronounced effect on the botanical composition of the sward in the longer term. Selection of a dominant species within the sward can give less abundant components a chance to compete, increasing community evenness and species richness. Conversely, the selection of minor components reduces sward compositional heterogeneity and hence plant species richness and evenness. Body size, gut type (foregut vs hindgut fermentation), physiological status (growing, pregnant, lactating), metabolic status (extent of body reserves) and environmental conditions all influence the nutrient requirements of a given animal and related foraging priorities. The diet selected is also strongly influenced by the availability of preferred food items, and their vertical and horizontal distribution within the sward. In general, larger animals, such as cattle and horses, are less selective grazers than smaller animals, such as sheep and goats. They are quicker to switch to consuming less-preferred sward components as the availability of preferred resources declines due to their greater forage demands, and as a result can be very effective in controlling competitive plant species consistently avoided by more selective grazers. As a result, low-intensity mixed grazing of cattle and sheep has been shown to improve the diversity and abundance of a range of taxa within grazed ecosystems. Mixed/co-species grazing with different animals exploiting different grassland resources is also associated with increased pasture use efficiency in terms of the use of different sward components and related improvements in nutritional value. In situations where cattle are not available, for example if they are not considered commercially viable, alternative species such as goats, ponies or South American camelids may offer an opportunity to diversify income streams and maintain productive and biodiverse pastures/grazing lands. Stocking rate and timing of grazing also have a considerable role in determining the impact of grazing. Regardless of the species grazing or the pasture grazed, grazing systems are dynamic since selective grazing impacts the future availability of sward components and subsequently dietary choices. New technologies under development provide opportunities to monitor plant/animal interactions more closely and in real time, which will in future support active management to deliver targeted biodiversity gains from specific sites.

Quantitative evaluation of aortic valve regurgitation in 4D flow cardiac magnetic resonance: at which level should we measure?

PURPOSE: To find the best level to measure aortic flow for quantification of aortic regurgitation (AR) in 4D flow CMR. METHODS: In 27 congenital heart disease patients with AR (67% male, 31 ± 16 years) two blinded observers measured antegrade, retrograde, net aortic flow volumes and regurgitant fractions at 6 levels in 4D flow: (1) below the aortic valve (AV), (2) at the AV, (3) at the aortic sinus, (4) at the sinotubular junction, (5) at the level of the pulmonary arteries (PA) and (6) below the brachiocephalic trunk. 2D phase contrast (2DPC) sequences were acquired at the level of PA. All patients received prior transthoracic echocardiography (TTE) with AR severity grading according to a recommended multiparametric approach. RESULTS: After assigning 2DPC measurements into AR grading, agreement between TTE AR grading and 2DPC was good (κ = 0.88). In 4D flow, antegrade flow was similar between the six levels (p = 0.87). Net flow was higher at level 1-2 than at levels 3-6 (p < 0.05). Retrograde flow and regurgitant fraction at level 1-2 were lower compared to levels 3-6 (p < 0.05). Reproducibility (inter-reader agreement: ICC 0.993, 95% CI 0.986-0.99; intra-reader agreement: ICC 0.982, 95%CI 0.943-0.994) as well as measurement agreement between 4D flow and 2DPC (ICC 0.994; 95%CI 0.989 - 0.998) was best at the level of PA. CONCLUSION: For estimating severity of AR in 4D flow, best reproducibility along with best agreement with 2DPC measurements can be expected at the level of PA. Measurements at AV or below AV might underestimate AR.

Preliminary experience with black bone magnetic resonance imaging for morphometry of the mandible and visualisation of the facial skeleton.

BACKGROUND: Children with orofacial deformity may require repeated imaging of the facial skeleton. OBJECTIVE: To test the feasibility and accuracy of "black bone" magnetic resonance imaging (MRI) for assessing facial deformity in children. MATERIALS AND METHODS: Three-dimensional (3-D) black bone gradient echo sequences (flip angle 5°, submillimetre spatial resolution) from 10 children (median age: 13 years, range: 2-16 years), who underwent MRI of the temporomandibular joints, were evaluated with multiplanar reconstruction and 3-D rendering tools. Intra- and inter-reader agreement was investigated for measuring the height of the mandibular ramus and condyle, basal length of the mandible, gonion angle and mandibular inclination angle by intraclass correlation coefficient (ICC) and Bland-Altman analysis. Absolute percentage error was calculated with the average of all measurements serving as reference. RESULTS: Sixty linear and 40 angle measurements were obtained on reformatted multiplanar black bone images with excellent inter-reader agreement (ICC > 0.99, agreement bias < 1.4 mm/ < 1.5°) and small error (median absolute error < 3%). The black bone images required inversion of the signal intensity and removal of air before they could be processed with standard volume rendering tools. The diagnostic utility of 3-D views for assessing the facial skeleton was sufficient except for assessing dental relationship. CONCLUSION: Morphometric measurements of the mandible can be obtained from black bone MRI with comparable inter-rater agreement to that reported for cone beam computed tomography (CT). With improvements of 3-D rendering techniques and software, black bone MRI may become a radiation-free alternative to CT in children with facial deformities.

Review: New feeds and new feeding systems in intensive and semi-intensive forage-fed ruminant livestock systems.

The contributions that ruminant livestock make to greenhouse gas and other pollutant emissions are well documented and of considerable policy and public concern. At the same time, livestock production continues to play an important role in providing nutrient-rich foodstuffs for many people, particularly in less developed countries. They also offer a means by which plants that cannot be digested by humans, e.g. grass, can be converted into human-edible protein. In this review, we consider opportunities to improve nutrient capture by ruminant livestock through new feeds and feeding systems concentrating on intensive and semi-intensive systems, which we define as those in which animals are given diets that are designed and managed to be used as efficiently as possible. We consider alternative metrics for quantifying efficiency, taking into account resource use at a range of scales. Mechanisms for improving the performance and efficiencies of both individual animals and production systems are highlighted. We then go on to map these to potential changes in feeds and feeding systems. Particular attention is given to improving nitrogen use efficiency and reducing enteric methane production. There is significant potential for the use of home-grown crops or novel feedstuffs such as insects and macroalgae to act as alternative sources of key amino acids and reduce reliance on unsustainably grown soybeans. We conclude by highlighting the extent to which climate change could impact forage-based livestock production and the need to begin work on developing appropriate adaptation strategies.

Neutrophil-to-lymphocyte ratio and outcomes in patients with new-onset or worsening heart failure with reduced and preserved ejection fraction.

AIMS: Inflammation is thought to play a role in heart failure (HF) pathophysiology. Neutrophil-to-lymphocyte ratio (NLR) is a simple, routinely available measure of inflammation. Its relationship with other inflammatory biomarkers and its association with clinical outcomes in addition to other risk markers have not been comprehensively evaluated in HF patients. METHODS: We evaluated patients with worsening or new-onset HF from the BIOlogy Study to Tailored Treatment in Chronic Heart Failure (BIOSTAT-CHF) study who had available NLR at baseline. The primary outcome was time to all-cause mortality or HF hospitalization. Outcomes were validated in a separate HF population. RESULTS: 1622 patients were evaluated (including 523 ventricular ejection fraction [LVEF] < 40% and 662 LVEF ≥ 40%). NLR was significantly correlated with biomarkers related to inflammation as well as NT-proBNP. NLR was significantly associated with the primary outcome in patients irrespective of LVEF (hazard ratio [HR] 1.18 per standard deviation increase; 95% confidence interval [CI] 1.11-1.26, P < 0.001). Patients with NLR in the highest tertile had significantly worse outcome than those in the lowest independent of LVEF (<40%: HR 2.75; 95% CI 1.84-4.09, P < 0.001; LVEF ≥ 40%: HR 1.51; 95% CI 1.05-2.16, P = 0.026). When NLR was added to the BIOSTAT-CHF risk score, there were improvements in integrated discrimination index (IDI) and net reclassification index (NRI) for occurrence of the primary outcome (IDI + 0.009; 95% CI 0.00-0.019, P = 0.030; continuous NRI + 0.112, 95% CI 0.012-0.176, P = 0.040). Elevated NLR was similarly associated with adverse outcome in the validation cohort. Decrease in NLR at 6 months was associated with reduced incidence of the primary outcome (HR 0.75; 95% CI 0.57-0.98, P = 0.036). CONCLUSIONS: Elevated NLR is significantly associated with elevated markers of inflammation in HF patients and is associated with worse outcome. Elevated NLR might potentially be useful in identifying high-risk HF patients and may represent a treatment target.

Assessment of ventricular flow dynamics by 4D-flow MRI in patients following surgical repair of d-transposition of the great arteries.

OBJECTIVES: To use 4D-flow MRI to describe systemic and non-systemic ventricular flow organisation and energy loss in patients with repaired d-transposition of the great arteries (d-TGA) and normal subjects. METHODS: Pathline tracking of ventricular volumes was performed using 4D-flow MRI data from a 1.5-T GE Discovery MR450 scanner. D-TGA patients following arterial switch (n = 17, mean age 14 ± 5 years) and atrial switch (n = 15, 35 ± 6 years) procedures were examined and compared with subjects with normal cardiac anatomy and ventricular function (n = 12, 12 ± 3 years). Pathlines were classified by their passage through the ventricles as direct flow, retained inflow, delayed ejection flow, and residual volume and visually and quantitatively assessed. Additionally, viscous energy losses (ELv) were calculated. RESULTS: In normal subjects, the ventricular flow paths were well ordered following similar trajectories through the ventricles with very little mixing of flow components. The flow paths in all atrial and some arterial switch patients were more irregular with high mixing. Direct flow and delayed ejection flow were decreased in atrial switch patients' systemic ventricles with a corresponding increase in residual volume compared with normal subjects (p = 0.003 and p < 0.001 respectively) and arterial switch patients (p < 0.0001 and p < 0.001 respectively). In non-systemic ventricles, arterial switch patients had increased direct flow and decreased delayed ejection fractions compared to normal (p = 0.007 and p < 0.001 respectively) and atrial switch patients (p = 0.01 and p < 0.001 respectively). Regions of high levels of mixing of ventricular flow components showed elevated ELv. CONCLUSIONS: 4D-flow MRI pathline tracking reveals disordered ventricular flow patterns and associated ELv in d-TGA patients. KEY POINTS: • 4D-flow MRI can be used to assess intraventricular flow dynamics in d-TGA patients. • d-TGA arterial switch patients mostly show intraventricular flow dynamics representative of normal subjects, while atrial switch patients show increased flow disorder and different proportions of intraventricular flow volumes. • Flow disruption and disorder increase viscous energy losses.

A novel presenilin 1 duplication mutation (Ile168dup) causing Alzheimer's disease associated with myoclonus, seizures and pyramidal features.

Mutations in the Presenilin 1 (PSEN1) gene are the most common cause of autosomal dominant familial Alzheimer's disease. We report the clinical, imaging and postmortem findings of kindred carrying a novel duplication mutation (Ile168dup) in the PSEN1 gene. We interpret the pathogenicity of this novel variant and discuss the additional neurological features (pyramidal dysfunction, myoclonus and seizures) that accompanied cognitive decline. This report broadens the clinical phenotype of PSEN1 insertion mutations while also highlighting the importance of considering duplication, insertion and deletion mutations in cases of young onset dementia.

Integrating Narcissus-derived galanthamine production into traditional upland farming systems.

Alzheimer's disease (AD) is a disorder associated with progressive degeneration of memory and cognitive function. Galantamine is a licenced treatment for AD but supplies of the plant alkaloid that it is produced from, galanthamine, are limited. This three-year system study tested the potential to combine Narcissus-derived galanthamine production with grassland-based ruminant production. Replicate plots of permanent pasture were prepared with and without bulbs of Narcissus pseudonarcissus sown as lines into the sward. Two different fertiliser regimes were imposed. The above-ground green biomass of N. pseudonarcissus was harvested in early spring and the galanthamine yield determined. In the second harvest year a split-plot design was implemented with lines of N. pseudonarcissus cut annually and biennially. All plots were subsequently grazed by ewes and lambs and animal performance recorded. Incorporation of N. pseudonarcissus into grazed permanent pasture had no detrimental effects on the health or performance of the sheep which subsequently grazed the pasture. There was no consistency to the effects of fertiliser rates on galanthamine yields. There was no difference in overall galanthamine yield if N. pseudonarcissus was cut biennially (1.64 vs. 1.75 kg galanthamine/ha for annual combined vs biennial cuts respectively; s.e.d = 0.117 kg galanthamine/ha; ns). This study verified the feasibility of a dual cropping approach to producing plant-derived galanthamine.

Additional value and new insights by four-dimensional flow magnetic resonance imaging in congenital heart disease: application in neonates and young children.

Cardiovascular MRI has become an essential imaging modality in children with congenital heart disease (CHD) in the last 15-20 years. With use of appropriate sequences, it provides important information on cardiovascular anatomy, blood flow and function for initial diagnosis and post-surgical or -interventional monitoring in children. Although considered as more sophisticated and challenging than CT, in particular in neonates and infants, MRI is able to provide information on intra- and extracardiac haemodynamics, in contrast to CT. In recent years, four-dimensional (4-D) flow MRI has emerged as an additional MR technique for retrospective assessment and visualisation of blood flow within the heart and any vessel of interest within the acquired three-dimensional (3-D) volume. Its application in young children requires special adaptations for the smaller vessel size and faster heart rate compared to adolescents or adults. In this article, we provide an overview of 4-D flow MRI in various types of complex CHD in neonates and infants to demonstrate its potential indications and beneficial application for optimised individual cardiovascular assessment. We focus on its application in clinical routine cardiovascular workup and, in addition, show some examples with pathologies other than CHD to highlight that 4-D flow MRI yields new insights in disease understanding and therapy planning. We shortly review the essentials of 4-D flow data acquisition, pre- and post-processing techniques in neonates, infants and young children. Finally, we conclude with some details on accuracy, limitations and pitfalls of the technique.

Early conscious prone positioning in patients with COVID-19 receiving continuous positive airway pressure: a retrospective analysis.

The global pandemic of COVID-19 has challenged the management of hypoxaemic respiratory failure and strained intensive care unit resources. While prone positioning (PP) is an established therapy in mechanically ventilated patients with acute respiratory distress syndrome (ARDS), its role in conscious patients is less well defined. We retrospectively reviewed our experience of implementing early PP in a cohort of 24 patients with acute hypoxaemic respiratory failure due to COVID-19 who required support with continuous positive airway pressure (CPAP). The use of PP alongside CPAP significantly increased both the ROX index and arterial oxygen pressure:fractional inspired oxygen (PaO2:FiO2) ratio from baseline values (ROX index: 7.0±2.5 baseline vs 11.4±3.7 CPAP+PP, p<0.0001; PaO2:FiO2 ratio: 143±73 mm Hg baseline vs 252±87 mm Hg CPAP+PP, p<0.01), and the changes to both the ROX index and PaO2:FiO2 ratio remained significant 1 hour after cessation of proning. The mean duration of PP in the first 24 hours was 8±5 hours. Few complications were observed and PP was continued for a mean of 10±5 days. From our experience in a dedicated COVID-19 respiratory high care unit, PP alongside CPAP therapy was feasible, tolerated, safe and improved oxygenation. The use of conscious PP in ARDS warrants further investigation in randomised controlled trials.

Flow quantification dependency on background phase correction techniques in 4D-flow MRI.

PURPOSE: To analyze the dependence of flow volume measurements on 3D cine phase-contrast MRI (4D-flow MRI) background phase correction. METHODS: In 31 subjects scanned on a 1.5T MRI scanner, flow volume measurements at 4 vessels were made using phantom corrected 2D phase contrast and 4D flow with background phase correction performed by linear, second, third, and fourth-order polynomial fitting to static tissue. Variations in the amount and distribution of static tissue were made to investigate the influence on flow volume measurements. RESULTS: Bland Altman comparison of 2D phase-contrast and 4D-flow measurements showed low bias (2.3%-4.8%) and relatively large limits of agreement (13.5%-17.6%). Approximately half of this was attributable to sequence and physiological differences between the 2 scan sequences, demonstrated by smaller limits of agreement (5.3%-10.0%) when comparing 4D-flow measurements with differing background phase corrections. Using only 20% of available static tissue points for polynomial fitting resulted in only 1% difference in flow volume measurements. Using asymmetrically distributed static tissue or including nonstatic tissue for polynomial fitting yielded highly variable differences in flow volume measurements, which became more variable with increased polynomial order. Completely asymmetric static tissue selection resulted in high deviations in flow volume measurements (mean > 7%, max = 345%). CONCLUSION: Comparisons between 2D phase-contrast and 4D-flow volume measurements should consider influences from sequence and physiological differences. A subset of static tissue points may be used with low impact on flow measurements, but should avoid the inclusion of nonstatic tissue and avoid asymmetric distribution. Higher-order polynomial fits are more susceptible to inaccurate static tissue selection.

Home used, patient self-managed, brain-computer interface for the management of central neuropathic pain post spinal cord injury: usability study.

BACKGROUND: Central Neuropathic Pain (CNP) is a frequent chronic condition in people with spinal cord injury (SCI). Previously, we showed that using laboratory brain-computer interface (BCI) technology for neurofeedback (NFB) training, it was possible to reduce CNP in people with SCI. In this study, we show results of patient self-managed treatment in their homes with a BCI-NFB using a consumer EEG device. METHODS: Users: People with chronic SCI (17 M, 3 F, 50.6 ± 14.1 years old), and CNP ≥4 on a Visual Numerical Scale. LOCATION: Laboratory training (up to 4 sessions) followed by home self-managed NFB. User Activity: Upregulating the EEG alpha band power by 10% above a threshold and at the same time downregulating the theta and upper beta (20-30 Hz) band power by 10% at electrode location C4. Technology: A consumer grade multichannel EEG headset (Epoch, Emotiv, USA), a tablet computer and custom made NFB software. EVALUATION: EEG analysis, before and after NFB assessment, interviews and questionnaires. RESULTS: Effectiveness: Out of 20 initially assessed participants, 15 took part in the study. Participants used the system for 6.9 ± 5.5 (median 4) weeks. Twelve participants regulated their brainwaves in a frequency specific manner and were most successful upregulating the alpha band power. However they typically upregulated power around their individual alpha peak (7.6 ± 0.8 Hz) that was lower than in people without CNP. The reduction in pain experienced was statistically significant in 12 and clinically significant (greater than 30%) in 8 participants. Efficiency: The donning was between 5 and 15 min, and approximately 10-20% of EEG data recorded in the home environment was noise. Participants were mildly stressed when self-administering NFB at home (2.4 on a scale 1-10). User satisfaction: Nine participants who completed the final assessment reported a high level of satisfaction (QUESQ, 4.5 ± 0.8), naming effectiveness, ease of use and comfort as main priorities. The main factors influencing frequency of NFB training were: health related issues, free time and pain intensity. CONCLUSION: Portable NFB is a feasible solution for home-based self-managed treatment of CNP. Compared to pharmacological treatments, NFB has less side effects and provides users with active control over pain. TRIAL REGISTRATION: GN15NE124 , Registered 9th June 2016.

Impact of Insecure Immigration Status and Ethnicity on Antenatal Mental Health Among Migrant Women.

OBJECTIVE: There is limited evidence on the prevalence and odds of antenatal common mental disorders (CMDs) among migrant women and the effect on risk of intersecting variables such as immigration status and ethnicity. This study aimed to estimate the prevalence and odds of antenatal CMDs among migrant women compared to UK-born women in an inner-London maternity service. METHODS: A cross-sectional survey stratified by response to depression screening questions was administered at first antenatal appointment. CMDs were assessed using the Structured Clinical Interview for DSM-IV. Recruitment took place between November 2014 and June 2016. RESULTS: Prevalence of antenatal CMDs was 21% (95% CI, 16-28) among migrant women (n = 283) and 24% (95% CI, 18-31) among UK-born women (n = 262). There was no significant difference in the odds of CMDs among migrant women compared to UK-born women (OR = 0.86; P = .57; 95% CI, 0.51-1.44). Migrant women, particularly those with insecure immigration status, had increased odds of posttraumatic stress disorder (OR = 29.08; P < .01; 95% CI, 4-188). When analyses were stratified by ethnicity, there was no effect of migrant status for white women, but for ethnic minority (nonwhite) women, migrant status decreased odds of having a CMD (OR = 0.31; P = .02; 95% CI, 0.12-0.82). CONCLUSIONS: Antenatal common mental disorders are prevalent among migrant women, but migrant status is unlikely to increase risk on its own. Immigration status, ethnicity, and other intersecting variables of social disadvantage must be investigated simultaneously to examine the perinatal mental health of heterogeneous migrant populations.

Revealing the Hippocampal Connectome through Super-Resolution 1150-Direction Diffusion MRI.

The hippocampus is a key component of emotional and memory circuits and is broadly connected throughout the brain. We tracked the whole-brain connections of white matter fibres from the hippocampus using ultra-high angular resolution diffusion MRI in both a single 1150-direction dataset and a large normal cohort (n = 94; 391-directions). Using a connectomic approach, we identified six dominant pathways in terms of strength, length and anatomy, and characterised them by their age and gender variation. The strongest individual connection was to the ipsilateral thalamus. There was a strong age dependence of hippocampal connectivity to medial occipital regions. Overall, our results concur with preclinical and ex-vivo data, confirming that meaningful in vivo characterisation of hippocampal connections is possible in an individual. Our findings extend the collective knowledge of hippocampal anatomy, highlighting the importance of the spinal-limbic pathway and the striking lack of hippocampal connectivity with motor and sensory cortices.

ADAMTS-9 in Mouse Cartilage Has Aggrecanase Activity That Is Distinct from ADAMTS-4 and ADAMTS-5.

A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4 and ADAMTS-5 are the principal aggrecanases in mice and humans; however, mice lacking the catalytic domain of both enzymes (TS-4/5∆cat) have no skeletal phenotype, suggesting there is an alternative aggrecanase for modulating normal growth and development in these mice. We previously identified aggrecanase activity that (a) cleaved at E↓G rather than E↓A bonds in the aggrecan core protein, and (b) was upregulated by retinoic acid but not IL-1α. The present study aimed to identify the alternative aggrecanase. Femoral head cartilage explants from TS-4/5∆cat mice were stimulated with IL-1α or retinoic acid and total RNA was analysed by microarray. In addition to ADAMTS-5 and matrix metalloproteinase (MMP)-13, which are not candidates for the novel aggrecanase, the microarray analyses identified MMP-11, calpain-5 and ADAMTS-9 as candidate aggrecanases upregulated by retinoic acid. When calpain-5 and MMP-11 failed to meet subsequent criteria, ADAMTS-9 emerged as the most likely candidate for the novel aggrecanase. Immunohistochemistry revealed ADAMTS-9 expression throughout the mouse growth plate and strong expression, particularly in the proliferative zone of the TS-4/5-∆cat mice. In conclusion, ADAMTS-9 has a novel specificity for aggrecan, cleaving primarily at E↓G rather than E↓A bonds in mouse cartilage. ADAMTS-9 might have more important roles in normal skeletal development compared with ADAMTS-4 and ADAMTS-5, which have key roles in joint pathology.