The relationship between MEG and fMRI

In recent years functional neuroimaging techniques such as fMRI, MEG, EEG and PET have provided researchers with a wealth of information on human brain function. However none of these modalities can measure directly either the neuro-electrical or neuro-chemical processes that mediate brain function. This means that metrics directly reflecting brain ‘activity’ must be inferred from other metrics (e.g. magnetic fields (MEG) or haemodynamics (fMRI)). To overcome this limitation, many studies seek to combine multiple complementary modalities and an excellent example of this is the combination of MEG (which has high temporal resolution) with fMRI (which has high spatial resolution). However, the full potential of multi-modal approaches can only be truly realised in cases where the relationship between metrics is known. In this paper, we explore the relationship between measurements made using fMRI and MEG. We describe the origins of the two signals as well as their relationship to electrophysiology. We review multiple studies that have attempted to characterise the spatial relationship between fMRI and MEG, and we also describe studies that exploit the rich information content of MEG to explore differing relationships between MEG and fMRI across neural oscillatory frequency bands. Monitoring the brain at “rest” has become of significant recent interest to the neuroimaging community and we review recent evidence comparing MEG and fMRI metrics of functional connectivity. A brief discussion of the use of magnetic resonance spectroscopy (MRS) to probe the relationship between MEG/fMRI and neurochemistry is also given. Finally, we highlight future areas of interest and offer some recommendations for the parallel use of fMRI and MEG

Accredited qualifications for capacity development in disaster risk reduction and climate change adaptation

Increasingly practitioners and policy makers working across the globe are recognising the importance of bringing together disaster risk reduction and climate change adaptation. From studies across 15 Pacific island nations, a key barrier to improving national resilience to disaster risks and climate change impacts has been identified as a lack of capacity and expertise resulting from the absence of sustainable accredited and quality assured formal training programmes in the disaster risk reduction and climate change adaptation sectors. In the 2016 UNISDR Science and Technology Conference on the Implementation of the Sendai Framework for Disaster Risk Reduction 2015–2030, it was raised that most of the training material available are not reviewed either through a peer-to-peer mechanism or by the scientific community and are, thus, not following quality assurance standards. In response to these identified barriers, this paper focuses on a call for accredited formal qualifications for capacity development identified in the 2015 United Nations landmark agreements in DRR and CCA and uses the Pacific Islands Region of where this is now being implemented with the launch of the Pacific Regional Federation of Resilience Professionals, for DRR and CCA. A key issue is providing an accreditation and quality assurance mechanism that is shared across boundaries. This paper argues that by using the United Nations landmark agreements of 2015, support for a regionally accredited capacity development that ensures all countries can produce, access and effectively use scientific information for disaster risk reduction and climate change adaptation. The newly launched Pacific Regional Federation of Resilience Professionals who work in disaster risk reduction and climate change adaptation may offer a model that can be used more widely

Quantifying the core deficit in classical schizophrenia

In the classical descriptions of schizophrenia, Kraepelin and Bleuler recognised disorganization and impoverishment of mental activity as fundamental symptoms. Their classical descriptions also included a tendency to persisting disability. The psychopathological processes underlying persisting disability in schizophrenia remain poorly understood. The delineation of a core deficit underlying persisting disability would be of value in predicting outcome and enhancing treatment. We tested the hypothesis that mental disorganization and impoverishment are associated with persisting impairments of cognition and role-function, and together reflect a latent core deficit that is discernible in cases diagnosed by modern criteria. We used Confirmatory Factor Analysis to determine whether measures of disorganisation, mental impoverishment, impaired cognition and role functioning in 40 patients with schizophrenia represent a single latent variable. Disorganization scores were computed from the variance shared between disorganization measures from three commonly used symptom scales. Mental impoverishment scores were computed similarly. A single factor model exhibited a good fit, supporting the hypothesis that these measures reflect a core deficit.Persisting brain disorders are associated with a reduction in Post Motor Beta Rebound (PMBR), the characteristic increase in electrophysiological beta amplitude that follows a motor response. Patients had significantly reduced PMBR compared with healthy controls. PMBR was negatively correlated with core deficit score.While the symptoms constituting impoverished and disorganised mental activity are dissociable in schizophrenia, nonetheless, the variance that these two symptom domains share with impaired cognition and role function, appears to reflect a pathophysiological process that might be described as the core deficit of classical schizophrenia

The common p.R114W <i>HNF4A </i>mutation causes a distinct clinical subtype of monogenic diabetes

HNF4A mutations cause increased birth weight, transient neonatal hypoglycaemia and maturity onset diabetes of the young (MODY). The most frequently reported HNF4A mutation is p.R114W (previously p.R127W) but functional studies have shown inconsistent results, there is lack of co-segregation in some pedigrees and an unexpectedly high frequency in public variant databases. We confirm that p.R114W is a pathogenic mutation with an odds ratio of 30.4 (95% CI: 9.79 - 125, P=2x10(-21)) for diabetes in our MODY cohort compared to controls. p.R114W heterozygotes do not have the increased birth weight of patients with other HNF4A mutations (3476g vs. 4147g, P=0.0004) and fewer patients responded to sulfonylurea treatment (48% vs. 73%, P=0.038). p.R114W has reduced penetrance; only 54% of heterozygotes developed diabetes by age 30 compared to 71% for other HNF4A mutations. We re-define p.R114W as a pathogenic mutation causing a distinct clinical subtype of HNF4A MODY with reduced penetrance, reduced sensitivity to sulfonylurea treatment and no effect on birth weight. This has implications for diabetes treatment, management of pregnancy and predictive testing of at-risk relatives. The increasing availability of large-scale sequence data is likely to reveal similar examples of rare, low-penetrance MODY mutations.</p

The plasma biomarker soluble SIGLEC-1 is associated with the type I interferon transcriptional signature, ethnic background and renal disease in systemic lupus erythematosus.

BACKGROUND: The molecular heterogeneity of autoimmune and inflammatory diseases has been one of the main obstacles to the development of safe and specific therapeutic options. Here, we evaluated the diagnostic and clinical value of a robust, inexpensive, immunoassay detecting the circulating soluble form of the monocyte-specific surface receptor sialic acid binding Ig-like lectin 1 (sSIGLEC-1). METHODS: We developed an immunoassay to measure sSIGLEC-1 in small volumes of plasma/serum from systemic lupus erythematosus (SLE) patients (n = 75) and healthy donors (n = 504). Samples from systemic sclerosis patients (n = 99) were studied as an autoimmune control. We investigated the correlation between sSIGLEC-1 and both monocyte surface SIGLEC-1 and type I interferon-regulated gene (IRG) expression. Associations of sSIGLEC-1 with clinical features were evaluated in an independent cohort of SLE patients (n = 656). RESULTS: Plasma concentrations of sSIGLEC-1 strongly correlated with expression of SIGLEC-1 on the surface of blood monocytes and with IRG expression in SLE patients. We found ancestry-related differences in sSIGLEC-1 concentrations in SLE patients, with patients of non-European ancestry showing higher levels compared to patients of European ancestry. Higher sSIGLEC-1 concentrations were associated with lower serum complement component 3 and increased frequency of renal complications in European patients, but not with the SLE Disease Activity Index clinical score. CONCLUSIONS: Our sSIGLEC-1 immunoassay provides a specific and easily assayed marker for monocyte-macrophage activation, and interferonopathy in SLE and other diseases. Further studies can extend its clinical associations and its potential use to stratify patients and as a secondary endpoint in clinical trials

Mode of birth and risk of infection-related hospitalisation in childhood: A population cohort study of 7.17 million births from 4 high-income countries

BACKGROUND: The proportion of births via cesarean section (CS) varies worldwide and in many countries exceeds WHO-recommended rates. Long-term health outcomes for children born by CS are poorly understood, but limited data suggest that CS is associated with increased infection-related hospitalisation. We investigated the relationship between mode of birth and childhood infection-related hospitalisation in high-income countries with varying CS rates. METHODS AND FINDINGS: We conducted a multicountry population-based cohort study of all recorded singleton live births from January 1, 1996 to December 31, 2015 using record-linked birth and hospitalisation data from Denmark, Scotland, England, and Australia (New South Wales and Western Australia). Birth years within the date range varied by site, but data were available from at least 2001 to 2010 for each site. Mode of birth was categorised as vaginal or CS (emergency/elective). Infection-related hospitalisations (overall and by clinical type) occurring after the birth-related discharge date were identified in children until 5 years of age by primary/secondary International Classification of Diseases, 10th Revision (ICD-10) diagnosis codes. Analysis used Cox regression models, adjusting for maternal factors, birth parameters, and socioeconomic status, with results pooled using meta-analysis. In total, 7,174,787 live recorded births were included. Of these, 1,681,966 (23%, range by jurisdiction 17%-29%) were by CS, of which 727,755 (43%, range 38%-57%) were elective. A total of 1,502,537 offspring (21%) had at least 1 infection-related hospitalisation. Compared to vaginally born children, risk of infection was greater among CS-born children (hazard ratio (HR) from random effects model, HR 1.10, 95% confidence interval (CI) 1.09-1.12, p < 0.001). The risk was higher following both elective (HR 1.13, 95% CI 1.12-1.13, p < 0.001) and emergency CS (HR 1.09, 95% CI 1.06-1.12, p < 0.001). Increased risks persisted to 5 years and were highest for respiratory, gastrointestinal, and viral infections. Findings were comparable in prespecified subanalyses of children born to mothers at low obstetric risk and unchanged in sensitivity analyses. Limitations include site-specific and longitudinal variations in clinical practice and in the definition and availability of some data. Data on postnatal factors were not available. CONCLUSIONS: In this study, we observed a consistent association between birth by CS and infection-related hospitalisation in early childhood. Notwithstanding the limitations of observational data, the associations may reflect differences in early microbial exposure by mode of birth, which should be investigated by mechanistic studies. If our findings are confirmed, they could inform efforts to reduce elective CS rates that are not clinically indicated

Eigenvalues of Dirichlet Laplacian within the class of open sets with constant diameter

This paper is about a shape optimization problem related to the Dirichlet Laplacian eingevalues in the Euclidean plane. More precisely we study the shape of the minimizer in the class of open sets of constant width. We prove that the disk is not a local minimizer except for a limited number of eigenvalues

Accredited qualifications for capacity development in disaster risk reduction and climate change adaptation

Increasingly practitioners and policy makers working across the globe are recognising the importance of bringing together disaster risk reduction and climate change adaptation. From studies across 15 Pacific island nations, a key barrier to improving national resilience to disaster risks and climate change impacts has been identified as a lack of capacity and expertise resulting from the absence of sustainable accredited and quality assured formal training programmes in the disaster risk reduction and climate change adaptation sectors. In the 2016 UNISDR Science and Technology Conference on the Implementation of the Sendai Framework for Disaster Risk Reduction 2015-2030, it was raised that most of the training material available are not reviewed either through a peer-to-peer mechanism or by the scientific community and are, thus, not following quality assurance standards. In response to these identified barriers, this paper focuses on a call for accredited formal qualifications for capacity development identified in the 2015 United Nations landmark agreements in DRR and CCA and uses the Pacific Islands Region of where this is now being implemented with the launch of the Pacific Regional Federation of Resilience Professionals, for DRR and CCA. A key issue is providing an accreditation and quality assurance mechanism that is shared across boundaries. This paper argues that by using the United Nations landmark agreements of 2015, support for a regionally accredited capacity development that ensures all countries can produce, access and effectively use scientific information for disaster risk reduction and climate change adaptation. The newly launched Pacific Regional Federation of Resilience Professionals who work in disaster risk reduction and climate change adaptation may offer a model that can be used more widely

Accredited qualifications for capacity development in disaster risk reduction and climate change adaptation

Increasingly practitioners and policy makers working across the globe are recognising the importance of bringing together disaster risk reduction and climate change adaptation. From studies across 15 Pacific island nations, a key barrier to improving national resilience to disaster risks and climate change impacts has been identified as a lack of capacity and expertise resulting from the absence of sustainable accredited and quality assured formal training programmes in the disaster risk reduction and climate change adaptation sectors. In the 2016 UNISDR Science and Technology Conference on the Implementation of the Sendai Framework for Disaster Risk Reduction 2015–2030, it was raised that most of the training material available are not reviewed either through a peer-to-peer mechanism or by the scientific community and are, thus, not following quality assurance standards. In response to these identified barriers, this paper focuses on a call for accredited formal qualifications for capacity development identified in the 2015 United Nations landmark agreements in DRR and CCA and uses the Pacific Islands Region of where this is now being implemented with the launch of the Pacific Regional Federation of Resilience Professionals, for DRR and CCA. A key issue is providing an accreditation and quality assurance mechanism that is shared across boundaries. This paper argues that by using the United Nations landmark agreements of 2015, support for a regionally accredited capacity development that ensures all countries can produce, access and effectively use scientific information for disaster risk reduction and climate change adaptation. The newly launched Pacific Regional Federation of Resilience Professionals who work in disaster risk reduction and climate change adaptation may offer a model that can be used more widely