Altered cerebellar connectivity in autism and cerebellar-mediated rescue of autism-related behaviors in mice

Altered cerebellar connectivity in autism and cerebellar-mediated rescue of autism-related behaviors in mice

Nature Neuroscience, Published online: 30 October 2017; doi:10.1038/s41593-017-0004-1

Cerebellar right Crus I (RCrusI) has been implicated in autism spectrum disorder (ASD). RCrusI modulation altered RCrusI–inferior parietal lobule connectivity, and this connectivity was atypical in children with ASD and in a TscI mouse model of ASD. Inhibition of RCrusI in mice led to autism-related behaviors, and RCrusI activation rescued social impairments in TscI mice.

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MRI of plaque characteristics and relationship with downstream perfusion and cerebral infarction in patients with symptomatic middle cerebral artery stenosis

Background

Intracranial plaque characteristics are associated with stroke events. Differences in plaque features may explain the disconnect between stenosis severity and the presence of ischemic stroke.

Purpose

To investigate the relationship between plaque characteristics and downstream perfusion changes, and their contribution to the occurrence of cerebral infarction beyond luminal stenosis.

Study Type

Case control.

Subjects

Forty-six patients with symptomatic middle cerebral artery (MCA) stenosis (with acute cerebral infarction, n = 30; without acute cerebral infarction, n = 16).

Field Strength/Sequence

3.0T with 3D turbo spin echo sequence (3D-SPACE).

Assessment

Luminal stenosis grade, plaque features including lesion T2 and T1 hyperintense components, plaque enhancement grade, and plaque distribution were assessed. Brain perfusion was evaluated on mean transient time maps based on the Alberta Stroke Program Early CT score (MTT-ASPECTS).

Statistical Tests

Plaque features, grade of luminal stenosis, and MTT-ASPECTS were compared between two groups. The association between plaque features and MTT-ASPECTS were assessed using Spearman’s correlation analysis. Multivariate logistic regression and receiver operating characteristic (ROC) curves were constructed to assess the effect of significant variables alone and their combination in determining the occurrence of cerebral infarction.

Results

Stronger enhanced plaques were associated with downstream lower MTT-ASPECTS (P = 0.010). Plaque enhancement grade (P = 0.039, odds ratio [OR] 5.9, 95% confidence interval [CI] 1.1–32) and MTT-ASPECTS (P = 0.003, OR 2.6, 95% CI 1.4–4.7) were associated with a recent cerebral infarction, whereas luminal stenosis grade was not (P = 0.128). The combination of MTT-ASPECTS and plaque enhancement grade provided incremental information beyond luminal stenosis grade alone. The area under the receiver operating characteristic curve (AUC) improved from 0.535 to 0.921 (P < 0.05).

Data Concusion

Strongly enhanced plaques are associated with a higher likelihood of downstream perfusion impairment. Plaque enhancement and perfusion evaluation may play a complementary role to luminal stenosis in determining the occurrence of acute cerebral infarction.

Level of Evidence: 4

Technical Efficacy: Stage 2

J. Magn. Reson. Imaging 2017.

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Automated vessel exclusion technique for quantitative assessment of hepatic iron overload by R2*-MRI

Background

Extraction of liver parenchyma is an important step in the evaluation of inline image-based hepatic iron content (HIC). Traditionally, this is performed by radiologists via whole-liver contouring and inline image-thresholding to exclude hepatic vessels. However, the vessel exclusion process is iterative, time-consuming, and susceptible to interreviewer variability.

Purpose

To implement and evaluate an automatic hepatic vessel exclusion and parenchyma extraction technique for accurate assessment of inline image-based HIC.

Study Type

Retrospective analysis of clinical data.

Subjects

Data from 511 MRI exams performed on 257 patients were analyzed.

Field Strength/Sequence

All patients were scanned on a 1.5T scanner using a multiecho gradient echo sequence for clinical monitoring of HIC.

Assessment

An automated method based on a multiscale vessel enhancement filter was investigated for three input data types—contrast-optimized composite image, inline image map, and inline image map—to segment blood vessels and extract liver tissue for inline image-based HIC assessment. Segmentation and inline image results obtained using this automated technique were compared with those from a reference inline image-thresholding technique performed by a radiologist.

Statistical Tests

The Dice similarity coefficient was used to compare the segmentation results between the extracted parenchymas, and linear regression and Bland-Altman analyses were performed to compare the inline image results, obtained with the automated and reference techniques.

Results

Mean liver inline image values estimated from all three filter-based methods showed excellent agreement with the reference method (slopes 1.04–1.05, R2 > 0.99, P < 0.001). Parenchyma areas extracted using the reference and automated methods had an average overlap area of 87–88%. The inline image-thresholding technique included small vessels and pixels at the vessel/tissue boundaries as parenchymal area, potentially causing a small bias (<5%) in inline image values compared to the automated method.

Data Conclusion

The excellent agreement between reference and automated hepatic vessel segmentation methods confirms the accuracy and robustness of the proposed method. This automated approach might improve the radiologist’s workflow by reducing the interpretation time and operator dependence for assessing HIC, an important clinical parameter that guides iron overload management.

Level of Evidence: 3

Technical Efficacy: Stage 2

J. Magn. Reson. Imaging 2017.

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Normative data on regional sweat-sodium concentrations of professional male team-sport athletes

Abstract

Background

The purpose of this paper was to report normative data on regional sweat sweat-sodium concentrations of various professional male team-sport athletes, and to compare sweat-sodium concentrations among sports. Data to this effect would inform our understanding of athlete sodium requirements, thus allowing for the individualisation of sodium replacement strategies. Accordingly, data from 696 athletes (Soccer, n = 270; Rugby, n = 181; Baseball, n = 133; American Football, n = 60; Basketball, n = 52) were compiled for a retrospective analysis. Regional sweat-sodium concentrations were collected using the pilocarpine iontophoresis method, and compared to self-reported measures collected via questionnaire.

Results

Sweat-sodium concentrations were significantly higher (p < 0.05) in American football (50.4 ± 15.3 mmol·L−1), baseball (54.0 ± 14.0 mmol·L−1), and basketball (48.3 ± 14.0 mmol·L−1) than either soccer (43.2 ± 12.0 mmol·L−1) or rugby (44.0 ± 12.1 mmol·L−1), but with no differences among the N.American or British sports. There were strong positive correlations between sweat-sodium concentrations and self-reported sodium losses in American football (r s = 0.962, p < 0.001), basketball (r s = 0.953, p < 0.001), rugby (r s = 0.813, p < 0.001), and soccer (r s = 0.748, p < 0.001).

Conclusions

The normative data provided on sweat-sodium concentrations might assist sports science/medicine practitioners in generating bespoke hydration and electrolyte-replacement strategies to meet the sodium demands of professional team-sport athletes. Moreover, these novel data suggest that self-reported measures of sodium loss might serve as an effective surrogate in the absence of direct measures; i.e., those which are more expensive or non-readily available.

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Eye tracking based navigation for proton beam therapy

Cancers of the eye, so-called ocular tumors, are a severe disease that may lead to blindness or even death if left untreated. A possibility to remove the tumor from the body of the patient is a so-called enucleation surgery, the removal of the eye. However, it is a drastic action and oncologists usually try to avoid it. Another treatment option is the therapy with protons. The actual proton therapy to treat ocular tumors is very successful and non-invasive. However, the navigation method that is applied for this kind of therapy requires a pre-treatment surgery, where radio-opaque clips are sutured onto the affected eyeball. These clips are used during the actual treatment to align the diseased eye with two orthogonal X-ray units. Hence, the overall treatment is invasive. The work at hand presents an alternative, completely non-invasive navigation method based on eye tracking technology. We present a new treatment scheme with a first eye tracking prototype integrated into the treatment facility at Paul Scherrer Institute (PSI). This system together with a patient specific eye model enables the medical physicist to align the patient’s eye such that the tumor gets accurately treated by the proton beam. Further, we present a second, improved eye tracking system. This time, we propose a stereo eye tracker, which only uses one physical camera to save physical space. We combine a stereo eye tracking algorithm with a clever arrangement of two planar mirrors and a single camera to get high accuracy, precision, and a compact design altogether. Finally, we present a method to quantitatively evaluate the proposed navigation system. Verifying the accuracy of the location estimate of a volunteer’s eye center is not easily possible. This is because the eye center is an intangible point, that does not correspond to an anatomical structure. Our evaluation method is based on an eye phantom on microstages and a corresponding kinematic model. Our research and development may lead to an ocular tumor treatment which will be safer, more cost-effective, and more accessible to patients suffering from this serious disease.

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Public trust and ‘ethics review’ as a commodity: the case of Genomics England Limited and the UK’s 100,000 genomes project

Abstract

The UK Chief Medical Officer’s 2016 Annual Report, Generation Genome, focused on a vision to fully integrate genomics into all aspects of the UK’s National Health Service (NHS). This process of integration, which has now already begun, raises a wide range of social and ethical concerns, many of which were discussed in the final Chapter of the report. This paper explores how the UK’s 100,000 Genomes Project (100 kGP)—the catalyst for Generation Genome, and for bringing genomics into the NHS—is negotiating these ethical concerns. The UK’s 100 kGP, promoted and delivered by Genomics England Limited (GEL), is an innovative venture aiming to sequence 100,000 genomes from NHS patients who have a rare disease, cancer, or an infectious disease. GEL has emphasised the importance of ethical governance and decision-making. However, some sociological critique argues that biomedical/technological organisations presenting themselves as ‘ethical’ entities do not necessarily reflect a space within which moral thinking occurs. Rather, the ‘ethical work’ conducted (and displayed) by organisations is more strategic, relating to the politics of the organisation and the need to build public confidence. We set out to explore whether GEL’s ethical framework was reflective of this critique, and what this tells us more broadly about how genomics is being integrated into the NHS in response to the ethical and social concerns raised in Generation Genome. We do this by drawing on a series of 20 interviews with individuals associated with or working at GEL.

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Antibiotic prophylaxis in clean-contaminated head and neck cases with microvascular free flap reconstruction: A systematic review and meta-analysis

Abstract

Background

Optimal antibiotic prophylaxis duration in head and neck clean-contaminated free-flap cases is unknown.

Methods

A systematic review/meta-analysis was conducted using PubMed/MEDLINE, Cochrane Library, Web-of-Science, and Scopus databases.

Results

Of the 3755 searched articles, 5 articles were included for a total of 861 patients. The recipient surgical site infection risk was significantly higher in patients receiving prophylactic antibiotics for ≤24 hours compared to >24 hours (relative risk [RR] 1.56; 95% confidence interval [CI] 1.13-2.14). In the post hoc multivariate analysis based on available individual-level data on 697 patients from 3 studies, the risk of surgical site infection for ≤24 hours versus >24 hours was not significant after adjusting for antibiotic type (RR 1.09; 95% CI 0.78-1.55). When compared to ampicillin-sulbactam, patients who received clindamycin prophylaxis had an increased likelihood of recipient surgical site infection (RR 2.85; 95% CI 1.95-4.17).

Conclusion

Less than or equal to 24 hours of antibiotic prophylaxis in head and neck clean-contaminated free-flap is likely sufficient but a strong conclusion remains elusive. Clindamycin prophylaxis increases the risk of recipient surgical site infection. Further prospective trials are necessary to clarify.

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