ACR White Paper on Magnetoencephalography and Magnetic Source Imaging: A Report from the ACR Commission on Neuroradiology.

Magnetoencephalography, the extracranial detection of tiny magnetic fields emanating from intracranial electrical activity of neurons, and its source modeling relation, magnetic source imaging, represent a powerful functional neuroimaging technique, able to detect and localize both spontaneous and evoked activity of the brain in health and disease. Recent years have seen an increased utilization of this technique for both clinical practice and research, in the United States and worldwide. This report summarizes current thinking, presents recommendations for clinical implementation, and offers an outlook for emerging new clinical indications.

Alterations in the Magnetoencephalography Default Mode Effective Connectivity following Concussion.

BACKGROUND AND PURPOSE: Magnetoencephalography is sensitive to functional connectivity changes associated with concussion. However, the directional influences between functionally related regions remain unexplored. In this study, we therefore evaluated concussion-related magnetoencephalography-based effective connectivity changes within resting-state default mode network regions. MATERIALS AND METHODS: Resting-state magnetoencephalography was acquired for 8 high school football players with concussion at 3 time points (preseason, postconcussion, postseason), as well as 8 high school football players without concussion and 8 age-matched controls at 2 time points (preseason, postseason). Time-series from the default mode network regions were extracted, and effective connectivity between them was computed for 5 different frequency bands. The default mode network regions were grouped into anterior and posterior default mode networks. The combined posterior-to-anterior and anterior-to-posterior effective connectivity values were averaged to generate 2 sets of values for each subject. The effective connectivity values were compared using a repeated measures ANOVA across time points for the concussed, nonconcussed, and control groups, separately. RESULTS: A significant increase in posterior-to-anterior effective connectivity from preseason to postconcussion (corrected P value = .013) and a significant decrease in posterior-to-anterior effective connectivity from postconcussion to postseason (corrected P value = .028) were observed in the concussed group. Changes in effective connectivity were only significant within the delta band. Anterior-to-posterior connectivity demonstrated no significant change. Effective connectivity in the nonconcussed group and controls did not show significant differences. CONCLUSIONS: The unidirectional increase in effective connectivity postconcussion may elucidate compensatory processes, invoking use of posterior regions to aid the function of susceptible anterior regions following brain injury. These findings support the potential value of magnetoencephalography in exploring directional changes of the brain network following concussion.

Prevalence and Incidence of Microhemorrhages in Adolescent Football Players.

BACKGROUND AND PURPOSE: SWI is an advanced imaging modality that is especially useful in cerebral microhemorrhage detection. Such microhemorrhages have been identified in adult contact sport athletes, and the sequelae of these focal bleeds are thought to contribute to neurodegeneration. The purpose of this study was to utilize SWI to determine whether the prevalence and incidence of microhemorrhages in adolescent football players are significantly greater than those of adolescent noncontact athletes. MATERIALS AND METHODS: Preseason and postseason SWI was performed and evaluated on 78 adolescent football players. SWI was also performed on 27 adolescent athletes who reported no contact sport history. Two separate one-tailed Fisher exact tests were performed to determine whether the prevalence and incidence of microhemorrhages in adolescent football players are greater than those of noncontact athlete controls. RESULTS: Microhemorrhages were observed in 12 football players. No microhemorrhages were observed in any controls. Adolescent football players demonstrated a significantly greater prevalence of microhemorrhages than adolescent noncontact controls (P = .02). Although 2 football players developed new microhemorrhages during the season, microhemorrhage incidence during 1 football season was not statistically greater in the football population than in noncontact control athletes (P = .55). CONCLUSIONS: Adolescent football players have a greater prevalence of microhemorrhages compared with adolescent athletes who have never engaged in contact sports. While microhemorrhage incidence during 1 season is not significantly greater in adolescent football players compared to adolescent controls, there is a temporal association between playing football and the appearance of new microhemorrhages.

Activity-dependent bulk endocytosis proteome reveals a key presynaptic role for the monomeric GTPase Rab11.

Activity-dependent bulk endocytosis (ADBE) is the dominant mode of synaptic vesicle endocytosis during high-frequency stimulation, suggesting it should play key roles in neurotransmission during periods of intense neuronal activity. However, efforts in elucidating the physiological role of ADBE have been hampered by the lack of identified molecules which are unique to this endocytosis mode. To address this, we performed proteomic analysis on purified bulk endosomes, which are a key organelle in ADBE. Bulk endosomes were enriched via two independent approaches, a classical subcellular fractionation method and isolation via magnetic nanoparticles. There was a 77% overlap in proteins identified via the two protocols, and these molecules formed the ADBE core proteome. Bioinformatic analysis revealed a strong enrichment in cell adhesion and cytoskeletal and signaling molecules, in addition to expected synaptic and trafficking proteins. Network analysis identified Rab GTPases as a central hub within the ADBE proteome. Subsequent investigation of a subset of these Rabs revealed that Rab11 both facilitated ADBE and accelerated clathrin-mediated endocytosis. These findings suggest that the ADBE proteome will provide a rich resource for the future study of presynaptic function, and identify Rab11 as a regulator of presynaptic function.

Secukinumab demonstrates greater sustained improvements in daily activities and personal relationships than ustekinumab in patients with moderate-to-severe plaque psoriasis: 52-week results from the CLEAR study.

BACKGROUND: Psoriasis can greatly impact patients' lives by influencing clothing worn as well as by impairing sexual functioning. Secukinumab, a human monoclonal antibody selectively neutralizing interleukin-17A, has demonstrated good efficacy and safety in the treatment of moderate-to-severe psoriasis and psoriatic arthritis with a rapid onset of action and sustained response. OBJECTIVE: This analysis using the CLEAR study, a phase 3b double-blind study comparing the efficacy and safety of secukinumab vs. ustekinumab in adults with moderate-to-severe plaque psoriasis, evaluated the treatment effects on patient's daily activities and personal relationships. METHODS: Impact on daily activities (interference with home/shopping/garden, and influence on clothes worn) and impact on personal relationships (problems with partner/others, and sexual difficulties) as well as their corresponding subscales were selected from the Dermatology Life Quality Index scale and evaluated for patients treated with secukinumab vs. ustekinumab from the CLEAR study. Treatment differences in mean scores and proportions of responders (score = 0, indicating no impact) were evaluated through 52 weeks. Time to response was evaluated through Week 16. RESULTS: Significant differences between secukinumab and ustekinumab were observed for daily activities and personal relationships at Week 16 and sustained through Week 52 (Week 52 response rates for daily activities: 82.9% vs. 73.5%, including interference with home/shopping/garden: 88.5% vs. 78.2%, and influence on clothes worn: 85.6% vs. 74.4%; personal relationships: 86.1% vs. 73.7%, including problems with partner/others: 86.6% vs. 74.8%, and sexual difficulties: 88.5% vs. 74.3%; all P < 0.01). The median time to response was 4 weeks for secukinumab vs. 8 weeks for ustekinumab for daily activities and personal relationships (both P < 0.05). CONCLUSION: Secukinumab treatment helps patients with moderate-to-severe plaque psoriasis have a more normal life faster when compared to ustekinumab, by providing greater and sustained improvement in clothing choice and sexual functioning.

The Overseas Registration Examination of the General Dental Council.

The Overseas Registration Examination is a route to entry to the UK Dentists Register for dentists who have qualified outside the European Economic Area. The role of the examination is to protect the public by ensuring that such dentists meet minimum standards of competence. Candidates invest considerable time and resource in attempting the examination. For these reasons it is essential that the examination is both robust and fair. This paper describes the fundamental principles of assessment underpinning the design of the examination and the steps taken by the General Dental Council's ORE Advisory Group to assure its ongoing quality.

Chronic mucocutaneous candidiasis: characterization of a family with STAT-1 gain-of-function and development of an ex-vivo assay for Th17 deficiency of diagnostic utility.

Chronic mucocutaneous candidiasis (CMC) is characterized by recurrent and persistent superficial infections, with Candida albicans affecting the mucous membranes, skin and nails. It can be acquired or caused by primary immune deficiencies, particularly those that impair interleukin (IL)-17 and IL-22 immunity. We describe a single kindred with CMC and the identification of a STAT1 GOF mutation by whole exome sequencing (WES). We show how detailed clinical and immunological phenotyping of this family in the context of WES has enabled revision of disease status and clinical management. Together with analysis of other CMC cases within our cohort of patients, we used knowledge arising from the characterization of this family to develop a rapid ex-vivo screening assay for the detection of T helper type 17 (Th17) deficiency better suited to the routine diagnostic setting than established in-vitro techniques, such as intracellular cytokine staining and enzyme-linked immunosorbent assay (ELISA) using cell culture supernatants. We demonstrate that cell surface staining of unstimulated whole blood for CCR6⁺ CXCR3⁻ CCR4⁺ CD161⁺ T helper cells generates results that correlate with intracellular cytokine staining for IL-17A, and is able to discriminate between patients with molecularly defined CMC and healthy controls with 100% sensitivity and specificity within the cohort tested. Furthermore, removal of CCR4 and CD161 from the antibody staining panel did not affect assay performance, suggesting that the enumeration of CCR6⁺ CXCR3⁻ CD4⁺ T cells is sufficient for screening for Th17 deficiency in patients with CMC and could be used to guide further investigation aimed at identifying the underlying molecular cause.

The autism and schizophrenia associated gene CYFIP1 is critical for the maintenance of dendritic complexity and the stabilization of mature spines.

Copy number variation (CNV) at the 15q11.2 region has been identified as a significant risk locus for neurological and neuropsychiatric conditions such as schizophrenia (SCZ) and autism spectrum disorder (ASD). However, the individual roles for genes at this locus in nervous system development, function and connectivity remain poorly understood. Haploinsufficiency of one gene in this region, Cyfip1, may provide a model for 15q11.2 CNV-associated neuropsychiatric phenotypes. Here we show that altering CYFIP1 expression levels in neurons both in vitro and in vivo influences dendritic complexity, spine morphology, spine actin dynamics and synaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor lateral diffusion. CYFIP1 is highly enriched at synapses and its overexpression in vitro leads to increased dendritic complexity. Neurons derived from Cyfip1 heterozygous animals on the other hand, possess reduced dendritic complexity, increased mobile F-actin and enhanced GluA2-containing AMPA receptor mobility at synapses. Interestingly, Cyfip1 overexpression or haploinsufficiency increased immature spine number, whereas activity-dependent changes in spine volume were occluded in Cyfip1 haploinsufficient neurons. In vivo, Cyfip1 heterozygous animals exhibited deficits in dendritic complexity as well as an altered ratio of immature-to-mature spines in hippocampal CA1 neurons. In summary, we provide evidence that dysregulation of CYFIP1 expression levels leads to pathological changes in CNS maturation and neuronal connectivity, both of which may contribute to the development of the neurological symptoms seen in ASD and SCZ.

Assessment of trace elements and legacy contaminant concentrations in California mussels (Mytilus spp.): relationship to land use and outfalls.

NOAA's Mussel Watch Program funded a regional pilot project in California that characterized contaminants associated with various land uses in conjunction with state, federal and private partners. Herein we assess the magnitude and distribution of trace elements and persistent organic contaminants in indigenous mussels with respect to land use, presence of outfalls and a subset of California Areas of Special Biological Significance (ASBS). We detected significant differences among the land use categories for the majority of trace elements and legacy contaminants measured. There was no significant difference between sites with and without outfalls. PCBs and PAHs were significantly lower in sites within ASBS boundary compared to other sites. The findings of this study will help fine tune future regional and national assessments as well as guide development of resource management and remediation activities and programs.

Automated white matter total lesion volume segmentation in diabetes.

BACKGROUND AND PURPOSE: WM lesion segmentation is often performed with the use of subjective rating scales because manual methods are laborious and tedious; however, automated methods are now available. We compared the performance of total lesion volume grading computed by use of an automated WM lesion segmentation algorithm with that of subjective rating scales and expert manual segmentation in a cohort of subjects with type 2 diabetes. MATERIALS AND METHODS: Structural T1 and FLAIR MR imaging data from 50 subjects with diabetes (age, 67.7 ± 7.2 years) and 50 nondiabetic sibling pairs (age, 67.5 ± 9.4 years) were evaluated in an institutional review board-approved study. WM lesion segmentation maps and total lesion volume were generated for each subject by means of the Statistical Parametric Mapping (SPM8) Lesion Segmentation Toolbox. Subjective WM lesion grade was determined by means of a 0-9 rating scale by 2 readers. Ground-truth total lesion volume was determined by means of manual segmentation by experienced readers. Correlation analyses compared manual segmentation total lesion volume with automated and subjective evaluation methods. RESULTS: Correlation between average lesion segmentation and ground-truth total lesion volume was 0.84. Maximum correlation between the Lesion Segmentation Toolbox and ground-truth total lesion volume (ρ = 0.87) occurred at the segmentation threshold of k = 0.25, whereas maximum correlation between subjective lesion segmentation and the Lesion Segmentation Toolbox (ρ = 0.73) occurred at k = 0.15. The difference between the 2 correlation estimates with ground-truth was not statistically significant. The lower segmentation threshold (0.15 versus 0.25) suggests that subjective raters overestimate WM lesion burden. CONCLUSIONS: We validate the Lesion Segmentation Toolbox for determining total lesion volume in diabetes-enriched populations and compare it with a common subjective WM lesion rating scale. The Lesion Segmentation Toolbox is a readily available substitute for subjective WM lesion scoring in studies of diabetes and other populations with changes of leukoaraiosis.

How pre-school children learn to brush their teeth in Sharjah, United Arab Emirates.

OBJECTIVE: The objective of this cross-sectional study was to assess tooth brushing habits of pre-school children and to determine the role and amount of supervision given to them by their parents. METHOD: One hundred pre-school children below 6 years were selected from Maternal and Child Health Center, Sharjah (United Arab Emirates, UAE). A standard piloted questionnaire was used to collect socio-demographic details and information on oral hygiene practise. RESULTS: Tooth brushing was stared at a mean age of 16 months. Thirty-seven per cent of the pre-schoolers used a toothbrush for cleaning their teeth and the brushing habits were mainly (70%) introduced by mothers. The majority (80%) of children's tooth brushing at the age of 3 years and above was supervised by mothers. Younger children were frequently supervised in tooth brushing than older children (P < 0.05) CONCLUSIONS: In summary, pre-school children of Sharjah (UAE) were introduced to tooth brushing at a mean age of 16 months. Mothers played a pivotal role in introducing and teaching the child how to brush. There was no positive correlation between the brushing behaviour of the mothers and their children. In most cases, the children's brushing was supervised by their mother when they were above 25 months of age. In children less than 12 months of age tooth brushing was not started at all.

Cholecystectomy deferral in patients with endoscopic sphincterotomy.

BACKGROUND: Cholecystectomy is not required in up to 64% of patients who adopt a wait-and-see policy after endoscopic clearance of common bile duct stones. Although reports of retrospective cohort series have shown a higher mortality among patients who defer cholecystectomy, it is not known if this is due to the patients' premorbid health status or due to the deferral of cholecystectomy. Randomised clinical trials of prophylactic cholecystectomy versus wait-and-see have not had sufficient power to demonstrate differences in survival. OBJECTIVES: To evaluate the beneficial and harmful effects of cholecystectomy deferral (wait-and-see) versus elective (prophylactic) cholecystectomy in patients who have had an endoscopic biliary sphincterotomy. SEARCH STRATEGY: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Controlled Trials Register (CENTRAL) in The Cochrane Library, MEDLINE (1966 to 2007), EMBASE (1980 to 2007), and Science Citation Index Expanded without language restrictions until April 2007. SELECTION CRITERIA: Randomised clinical trials comparing patients whose gallbladder was left in-situ after endoscopic sphincterotomy (wait-and-see group) versus patients who had cholecystectomy with either endoscopic sphincterotomy or common bile duct exploration (prophylactic cholecystectomy group), irrespective of blinding, language, or publication status. DATA COLLECTION AND ANALYSIS: We assessed the impact of a wait-and-see policy on mortality. Secondary outcomes assessed were the incidence of biliary pain, cholangitis, pancreatitis, need for cholangiography, need for cholecystectomy, and the rate of difficult cholecystectomy. We pooled data using relative risk with fixed-effect and random-effects models. MAIN RESULTS: We included 5 randomised trials with 662 participants out of 93 publications identified through the literature searches. The number of deaths was 47 in the wait-and-see group (334 patients) compared to 26 in the prophylactic cholecystectomy group (328 patients) for a 78% increased risk of mortality (RR 1.78, 95% CI 1.15 to 2.75, P = 0.010). The survival benefit of prophylactic cholecystectomy was independent of trial design, inclusion of high risk patients or inclusion of any one of the five trials. Patients in the wait-and-see group had higher rates of recurrent biliary pain (RR 14.56, 95% CI 4.95 to 42.78, P < 00001), jaundice or cholangitis (RR 2.53, 95% CI 1.09 to 5.87, P = 0.03), and of repeat ERCP or other forms of cholangiography (RR 2.36, 95% CI 1.29 to 4.32, P = 0.005). Cholecystectomy was eventually performed in 35% (115 patients) of the wait-and-see group. AUTHORS' CONCLUSIONS: Prophylactic cholecystectomy should be offered to patients whose gallbladders remain in-situ after endoscopic sphincterotomy and common bile duct clearance.

A globally applicable location-specific screening model for assessing the relative risk of pesticide leaching.

A screening model of pesticide leaching loss is described which forms part of a multi-criteria risk-based indicator system called PRoMPT (Pesticide Risk Management and Profiling Tool). The leaching model evaluates pesticide fate in soil for any application rate and time of application (including multiple applications), for any land-based location in the world. It considers a generic evaluative environment with fixed dimensions and soil properties. The soil profile is conceptualised as a number of discrete layers. Equilibrium partitioning between adsorbed and dissolved chemical (based on the organic carbon-water partition coefficient [K(OC)]) is assumed in each time step, in each layer. Non-leaching losses are described using first order kinetics. Drainage is assumed to be uniform throughout the soil profile but varies temporally. The drainage rate, which can be augmented by evapotranspiration-adjusted irrigation, is derived from long-term mean monthly water balance model calculations performed for 30 arc-minute grid cells across the entire ice-free land surface of the earth. Although, such predictions are approximate, they do capture the seasonality and relative magnitude of drainage and allow the model to be applied anywhere, without the need for extensive data compilation. PRoMPT predictions are shown to be consistent with those made by more sophisticated models (PRZM, PELMO and PEARL) for the FOCUS groundwater scenarios.

Inter-laboratory comparison of polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) in bleaching earth used in the refinement of edible oils.

Bleaching earth (dried, powdered, bentonite-montmorillonite clay) is commonly used as a processing aid in edible oil refinement. Used bleaching earth may be incorporated into animal feed indirectly, for example because it is included into seed meal, or directly (e.g., as a binding agent). Control must be demonstrated to ensure that the levels of polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) in feed ingredients do not infringe European Community regulations. The low legislative action level assigned is analytically challenging and may be at or below the limits of quantification achievable by many laboratories. A statistical comparison (following the IUPAC/ISO/AOAC protocol) was made of analyses of PCDDs and PCDFs in selected bleaching earth samples by laboratories from Europe and the USA to assess the comparability of data. Of 19 sets of results submitted by laboratories for replicate samples, 11 demonstrated acceptable agreement.

The effects of diet, breast-feeding and weaning on caries risk for pre-term and low birth weight children.

OBJECTIVES: The aims of this study were to determine the prevalence of dental disease in 3-4-year-old children born pre-term and low birth weight (PLBW) in East London, UK, to make comparisons with normal birth weight children (NBW), and to investigate the impact of dietary habits on the development of dental caries in primary teeth. DESIGN: This was a cross-sectional study. SUBJECTS AND METHODS: The subjects were 100 children (54 boys and 46 girls) with a mean age (+/- SD) of 41.70 +/- 5.11 months. The children were resident within walking distance of the dental hospital and were invited to attend with their parents. Demographic data and information about feeding practices from infancy to the present were ascertained by structured questionnaire. Dental caries status was determined, and height, weight and head circumference were also measured. RESULTS: Sixty children had experienced dental caries with a mean (+/- SD) dmft of 2.98 +/- 3.93, 25 of whom had a dmft greater than 5. Normal birth weight children (3.00 +/- 4.18) and boys (3.55 +/- 4.48) had a significantly increased dmft over PLBW children (2.95 +/- 3.35) and girls (2.29 +/- 3.04). The PLBW children were more likely to have used a bottle from birth and one in four children were still using a bottle at the time of the dental examination. The PLBW children were significantly more likely to eat sugar than NBW children, scoring 5.53 +/- 2.10 and 4.61 +/- 1.94, respectively. CONCLUSIONS: A clear relationship exists between poor diet and PLBW in a group of children resident in the East End of London. Targeted infant feeding programmes, education and support for families with regard to dental care is of importance to avoid an unnecessary amount of dental disease in young children.