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Aside from well-characterized immune-mediated ataxias with a clear trigger and/or association with specific neuronal antibodies, a large number of idiopathic ataxias are suspected to be immune mediated but remain undiagnosed due to lack of diagnostic biomarkers. Primary autoimmune cerebellar ataxia (PACA) is the term used to describe this later group. An International Task Force comprising experts in the field of immune ataxias was commissioned by the Society for Research on the Cerebellum and Ataxias (SRCA) in order to devise diagnostic criteria aiming to improve the diagnosis of PACA. The proposed diagnostic criteria for PACA are based on clinical (mode of onset, pattern of cerebellar involvement, presence of other autoimmune diseases), imaging findings (MRI and if available MR spectroscopy showing preferential, but not exclusive involvement of vermis) and laboratory investigations (CSF pleocytosis and/or CSF-restricted IgG oligoclonal bands) parameters. The aim is to enable clinicians to consider PACA when encountering a patient with progressive ataxia and no other diagnosis given that such consideration might have important therapeutic implications.

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Motion is a major confound in diffusion‐weighted imaging (DWI) in the body, and it is a common cause of image artefacts. The effects are particularly severe in cardiac applications, due to the nonrigid cyclical deformation of the myocardium. Spin echo‐based DWI commonly employs gradient moment‐nulling techniques to desensitise the acquisition to velocity and acceleration, ie, nulling gradient moments up to the 2nd order (M2‐nulled). However, current M2‐nulled DWI scans are limited to encode diffusion along a single direction at a time. We propose a method for designing b‐tensors of arbitrary shapes, including planar, spherical, prolate and oblate tensors, while nulling gradient moments up to the 2nd order and beyond. The design strategy comprises initialising the diffusion encoding gradients in two encoding blocks about the refocusing pulse, followed by appropriate scaling and rotation, which further enables nulling undesired effects of concomitant gradients. Proof‐of‐concept assessment of in vivo mean diffusivity (MD) was performed using linear and spherical tensor encoding (LTE and STE, respectively) in the hearts of five healthy volunteers. The results of the M2‐nulled STE showed that (a) the sequence was robust to cardiac motion, and (b) MD was higher than that acquired using standard M2‐nulled LTE, where diffusion‐weighting was applied in three orthogonal directions, which may be attributed to the presence of restricted diffusion and microscopic diffusion anisotropy. Provided adequate signal‐to‐noise ratio, STE could significantly shorten estimation of MD compared with the conventional LTE approach. Importantly, our theoretical analysis and the proposed gradient waveform design may be useful in microstructure imaging beyond diffusion tensor imaging where the effects of motion must be suppressed.  相似文献   
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European Archives of Oto-Rhino-Laryngology - The objective of this prospective, single-subject, repeated measures study was to evaluate the audiological benefit and patient satisfaction with an...  相似文献   
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Objectives

Improved fixation techniques with optional use of bone cements for implant augmentation have been developed to enhance stability and reduce complication rates after osteosynthesis of femoral neck fractures. This biomechanical study aimed to evaluate the effect of cement augmentation on implant anchorage and overall performance of screw-anchor fixation systems in unstable femoral neck fractures.

Methods

Ten pairs of human cadaveric femora were used to create standardized femoral neck fractures (Pauwels type 3 fractures; AO/OTA 31-B2) with comminution and were fixed by means of a rotationally stable screw-anchor (RoSA) system. The specimens were assigned pairwise to two groups and either augmented with PMMA-based cement (Group 1, augmented) or left without such augmentation (Group 2, control).Biomechanical testing, simulating physiological loading at four distinct load levels, was performed over 10.000 cycles for each level with the use of a multidimensional force-transducer system. Data was analysed by means of motion tracking.

Results

Stiffness, femoral head rotation, implant migration, femoral neck shortening, and failure load did not differ significantly between the two groups (p?≥?.10). For both groups, the main failure type was dislocation in the frontal plane with consecutive varus collapse). In the cement-augmented specimens, implant migration and femoral neck shortening were significantly dependent on bone mineral density (BMD), with higher values in osteoporotic bones. There was a correlation between failure load and BMD in cement-augmented specimens.

Conclusion

In screw-anchor fixation of unstable femoral neck fractures, bone-cement augmentation seems to show no additional advantages in regard to stiffness, rotational stability, implant migration, resistance to fracture displacement, femoral neck shortening or failure load.  相似文献   
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Background

We report the first-in-concept human trial of the safety, tolerability and immunogenicity when a novel TLR 7/8/RIG I agonist RNA-based adjuvant, CV8102, was administered alone or mixed with fractional doses of a licensed rabies vaccine (Rabipur®) as model antigen.

Methods

The primary objective was to assess the safety and reactogenicity of various dose levels of CV8102 alone or mixed with Rabipur® in healthy 18–40 year-old male volunteers. A secondary objective was to assess the immune-enhancing potential of bedside-mixes of CV8102 with fractional doses of Rabipur® by measuring induction of rabies virus neutralising titres (VNTs).

Results

Fifty-six volunteers received 50–100?μg CV8102 alone (n?=?11), bedside-mixed CV8102 and Rabipur® (n?=?20), or Rabipur® alone (n?=?25; control). When given alone or mixed with Rabipur® CV8102 caused mostly Grade 1 or 2 local or systemic reactogenicity, but no related SAEs. As 100?µg CV8102 was associated with marked CRP increases further dose escalation was stopped. Combining 25–50?µg of CV8102 with fractional doses of Rabipur® significantly improved the kinetics of VNT responses; 50?µg CV8102 also improved the magnitude of VNT responses to 1/10 Rabipur® but caused severe but self-limiting influenza-like symptoms in 2 of 14 subjects.

Conclusions

Doses of 25 and 50?µg CV8102 appeared safe and with an acceptable reactogenicity profile while significantly enhancing the immunogenicity of fractional doses of rabies vaccine.EudraCT No. 2013-004514-18.  相似文献   
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