Magnetic resonance imaging (MRI) scanning for research: the experiences of healthy volunteers and patients with remitted depressive illness

We report the findings from a study exploring the experiences of individuals undergoing MRI scanning for research. Semi structured interviews took place before and after scanning with 17 participants; 12 were healthy volunteers and 5 were patients with a diagnosis of remitted depression. Themes of apprehension and curiosity prior to scanning were common in both groups. Patients were often confused about the procedure. Negative feelings were an issue at the outset, characterised by shock related to the physical surroundings, after which positive feelings, for example relaxation, were often experienced, and in the case of patients, learning more about their brain. Written information about imaging was deemed satisfactory; however the ability to ‘experience’ aspects of scanning beforehand was suggested. Scanning may be viewed as a process beginning prior to the procedure itself and involving positive and negative emotions. Increased information, reassurance and a more interactive intervention to reduce anxiety may be beneficial and may improve individuals’ experience of this widely used procedure

Chest pain and shortness of breath in cardiovascular disease: a prospective cohort study in UK primary care.

OBJECTIVE: To determine characteristics associated with monthly chest pain and shortness of breath (SoB) during activity in cardiovascular disease (CVD) and trajectories of these symptoms over 10 months. STUDY DESIGN AND SETTING: Baseline questionnaire was sent to patients aged ≥40 years from 10 UK general practices. Responders were sent monthly questionnaires for 10 months. For patients with CVD (ischaemic heart disease and heart failure), the association of sociodemographic characteristics, pain elsewhere and anxiety and depression with monthly reports of chest pain and SoB during activity were determined using multilevel, multinomial logistic regression. Common symptom trajectories were determined using dual trajectory latent class growth analysis. RESULTS: 661 patients with CVD completed at least 5 monthly questionnaires. Multiple other pain sites (relative risk ratio: 4.03; 95% CI 1.64 to 9.91) and anxiety or depression (relative risk ratio: 3.31; 95% CI 1.89 to 5.79) were associated with reporting weekly chest pain. Anxiety or depression (relative risk ratio: 4.10; 95% CI 2.72 to 6.17), obesity (relative risk ratio: 2.53; 95% CI 1.49 to 4.30), older age (80+: relative risk ratio: 2.51; 95% CI 1.19 to 5.26), increasing number of pain sites (4+: relative risk ratio: 4.64; 95% CI 2.35 to 9.18) and female gender (relative risk ratio: 1.81; 95% CI 1.20 to 2.75) were associated with reporting weekly SoB. Eight symptom trajectories were identified, with SoB symptoms more common than chest pain. CONCLUSIONS: Potentially modifiable characteristics are associated with the experience of chest pain and SoB. Identified symptom trajectories may facilitate tailored care to improve outcomes in patients with CVD

Angles in Fuzzy Disc and Angular Noncommutative Solitons

The fuzzy disc, introduced by the authors of Ref.[1], is a disc-shaped region in a noncommutative plane, and is a fuzzy approximation of a commutative disc. In this paper we show that one can introduce a concept of angles to the fuzzy disc, by using the phase operator and phase states known in quantum optics. We gave a description of a fuzzy disc in terms of operators and their commutation relations, and studied properties of angular projection operators. A similar construction for a fuzzy annulus is also given. As an application, we constructed fan-shaped soliton solutions of a scalar field theory on a fuzzy disc, which corresponds to a fan-shaped D-brane. We also applied this concept to the theory of noncommutative gravity that we proposed in Ref.[2]. In addition, possible connections to black hole microstates, holography and an experimental test of noncommutativity by laser physics are suggested.Comment: 24 pages, 12 figures; v2: minor mistake corrected in Eq.(3.21), and discussion adapted accordingly; v3: a further discussion on the algebra of the fuzzy disc added in subsection 3.2; v4: discussions improved and typos correcte

Diffusion magnetic resonance imaging assessment of regional white matter maturation in preterm neonates

PURPOSE: Diffusion magnetic resonance imaging (dMRI) studies report altered white matter (WM) development in preterm infants. Neurite orientation dispersion and density imaging (NODDI) metrics provide more realistic estimations of neurite architecture in vivo compared with standard diffusion tensor imaging (DTI) metrics. This study investigated microstructural maturation of WM in preterm neonates scanned between 25 and 45 weeks postmenstrual age (PMA) with normal neurodevelopmental outcomes at 2 years using DTI and NODDI metrics. METHODS: Thirty-one neonates (n = 17 male) with median (range) gestational age (GA) 32+1 weeks (24+2-36+4) underwent 3 T brain MRI at median (range) post menstrual age (PMA) 35+2 weeks (25+3-43+1). WM tracts (cingulum, fornix, corticospinal tract (CST), inferior longitudinal fasciculus (ILF), optic radiations) were delineated using constrained spherical deconvolution and probabilistic tractography in MRtrix3. DTI and NODDI metrics were extracted for the whole tract and cross-sections along each tract to assess regional development. RESULTS: PMA at scan positively correlated with fractional anisotropy (FA) in the CST, fornix and optic radiations and neurite density index (NDI) in the cingulum, CST and fornix and negatively correlated with mean diffusivity (MD) in all tracts. A multilinear regression model demonstrated PMA at scan influenced all diffusion measures, GA and GAxPMA at scan influenced FA, MD and NDI and gender affected NDI. Cross-sectional analyses revealed asynchronous WM maturation within and between WM tracts.). CONCLUSION: We describe normal WM maturation in preterm neonates with normal neurodevelopmental outcomes. NODDI can enhance our understanding of WM maturation compared with standard DTI metrics alone

Exploring the multiple-hit hypothesis of preterm white matter damage using diffusion MRI.

Background: Preterm infants are at high risk of diffuse white matter injury and adverse neurodevelopmental outcome. The multiple hit hypothesis suggests that the risk of white matter injury increases with cumulative exposure to multiple perinatal risk factors. Our aim was to test this hypothesis in a large cohort of preterm infants using diffusion weighted magnetic resonance imaging (dMRI). Methods: We studied 491 infants (52% male) without focal destructive brain lesions born at < 34 weeks, who underwent structural and dMRI at a specialist Neonatal Imaging Centre. The median (range) gestational age (GA) at birth was 30+ 1 (23+ 2-33+ 5) weeks and median postmenstrual age at scan was 42+ 1 (38-45) weeks. dMRI data were analyzed using tract based spatial statistics and the relationship between dMRI measures in white matter and individual perinatal risk factors was assessed. We tested the hypothesis that increased exposure to perinatal risk factors was associated with lower fractional anisotropy (FA), and higher radial, axial and mean diffusivity (RD, AD, MD) in white matter. Neurodevelopmental performance was investigated using the Bayley Scales of Infant and Toddler Development, Third Edition (BSITD-III) in a subset of 381 infants at 20 months corrected age. We tested the hypothesis that lower FA and higher RD, AD and MD in white matter were associated with poorer neurodevelopmental performance. Results: Identified risk factors for diffuse white matter injury were lower GA at birth, fetal growth restriction, increased number of days requiring ventilation and parenteral nutrition, necrotizing enterocolitis and male sex. Clinical chorioamnionitis and patent ductus arteriosus were not associated with white matter injury. Multivariate analysis demonstrated that fetal growth restriction, increased number of days requiring ventilation and parenteral nutrition were independently associated with lower FA values. Exposure to cumulative risk factors was associated with reduced white matter FA and FA values at term equivalent age were associated with subsequent neurodevelopmental performance. Conclusion: This study suggests multiple perinatal risk factors have an independent association with diffuse white matter injury at term equivalent age and exposure to multiple perinatal risk factors exacerbates dMRI defined, clinically significant white matter injury. Our findings support the multiple hit hypothesis for preterm white matter injury

IL-6 and IL-27 play both distinct and redundant roles in regulating CD4 T-cell responses during chronic viral infection

The IL-6 cytokine family signals through the common signal transduction molecule gp130 combined with a cytokine-specific receptor. Gp130 signaling on CD4 T cells is vital in controlling chronic infection of mice with lymphocytic choriomeningitis virus clone 13 (LCMV Cl13), but the precise role of individual members of the IL-6 cytokine family is not fully understood. Transcriptional analysis highlighted the importance of gp130 signaling in promoting key processes in CD4 T cells after LCMV Cl13 infection, particularly genes associated with T follicular helper (Tfh) cell differentiation and IL-21 production. Further, Il27r−/−Il6ra−/− mice failed to generate antibody or CD8 T-cell immunity and to control LCMV Cl13. Transcriptomics and phenotypic analyses of Il27r−/−Il6ra−/− Tfh cells revealed that IL-6R and IL-27R signaling was required to activate key pathways within CD4 T cells. IL-6 and IL-27 signaling has distinct and overlapping roles, with IL-6 regulating Tfh differentiation, IL-27 regulating CD4 T cell survival, and both redundantly promoting IL-21

Vaccination against Foot-and-mouth disease : do initial conditions affect its benefit?

When facing incursion of a major livestock infectious disease, the decision to implement a vaccination programme is made at the national level. To make this decision, governments must consider whether the benefits of vaccination are sufficient to outweigh potential additional costs, including further trade restrictions that may be imposed due to the implementation of vaccination. However, little consensus exists on the factors triggering its implementation on the field. This work explores the effect of several triggers in the implementation of a reactive vaccination-to-live policy when facing epidemics of foot-and-mouth disease. In particular, we tested whether changes in the location of the incursion and the delay of implementation would affect the epidemiological benefit of such a policy in the context of Scotland. To reach this goal, we used a spatial, premises-based model that has been extensively used to investigate the effectiveness of mitigation procedures in Great Britain. The results show that the decision to vaccinate, or not, is not straightforward and strongly depends on the underlying local structure of the population-at-risk. With regards to disease incursion preparedness, simply identifying areas of highest population density may not capture all complexities that may influence the spread of disease as well as the benefit of implementing vaccination. However, if a decision to vaccinate is made, we show that delaying its implementation in the field may markedly reduce its benefit. This work provides guidelines to support policy makers in their decision to implement, or not, a vaccination-to-live policy when facing epidemics of infectious livestock disease

Demonstration of a Melanoma-Specific CD44 Alternative Splicing Pattern That Remains Qualitatively Stable, but Shows Quantitative Changes during Tumour Progression

The role of CD44 in the progression of human melanoma has mostly been characterised by qualitative changes in expression of its individual variable exons. These exons however, may be expressed to form a number of molecules, the alternative splice variants of CD44, which may be structurally and functionally different. Using real-time PCR measurements with variable exon specific primers we have determined that all are expressed in human melanoma. To permit comparison between different tumours we identified a stable CD44 variable exon (CD44v) expression pattern, or CD44 ‘fingerprint’. This was found to remain unchanged in melanoma cell lines cultured in different matrix environments. To evaluate evolution of this fingerprint during tumour progression we established a scid mouse model, in which the pure expression pattern of metastatic primary tumours, circulating cells and metastases, non-metastatic primary tumours and lung colonies could be studied. Our analyses demonstrated, that although the melanoma CD44 fingerprint is qualitatively stable, quantitative changes are observed suggesting a possible role in tumour progression

Multimorbidity in bipolar disorder and under-treatment of cardiovascular disease: a cross sectional study

Background: Individuals with serious mental disorders experience poor physical health, especially increased rates of cardiometabolic morbidity and premature morbidity. Recent evidence suggests that individuals with schizophrenia have numerous comorbid physical conditions which may be under-recorded and under-treated but to date very few studies have explored this issue for bipolar disorder. Methods:We conducted a cross-sectional analysis of a dataset of 1,751,841 registered patients within 314 primary-care practices in Scotland, U.K. Bipolar disorder was identified using Read Codes recorded within electronic medical records. Data on 32 common chronic physical conditions were also assessed. Potential prescribing inequalities were evaluated by analyzing prescribing data for coronary heart disease (CHD) and hypertension. Results: Compared to controls, individuals with bipolar disorder were significantly less likely to have no recorded physical conditions (OR 0.59, 95% CI 0.54-0.63) and significantly more likely to have one physical condition (OR 1.27, 95% CI 1.16-1.39), two physical conditions (OR 1.45, 95% CI 1.30-1.62) and three or more physical conditions (OR 1.44, 95% CI 1.30-1.64). People with bipolar disorder also had higher rates of thyroid disorders, chronic kidney disease, chronic pain, chronic obstructive airways disease and diabetes but, surprisingly, lower recorded rates of hypertension and atrial fibrillation. People with bipolar disorder and comorbid CHD or hypertension were significantly more likely to be prescribed no antihypertensive or cholesterol-lowering medications compared to controls, and bipolar individuals with CHD or hypertension were significantly less likely to be on 2 or more antihypertensive agents. Conclusions: Individuals with bipolar disorder are similar to individuals with schizophrenia in having a wide range of comorbid and multiple physical health conditions. They are also less likely than controls to have a primary-care record of cardiovascular conditions such as hypertension and atrial fibrillation. Those with a recorded diagnosis of CHD or hypertension were less likely to be treated with cardiovascular medications and were treated less intensively. This study highlights the high physical healthcare needs of people with bipolar disorder, and provides evidence for a systematic under-recognition and under-treatment of cardiovascular disease in this group