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Magnetic resonance imaging (MRI) has become an unrivalled medical diagnostic technique able to map tissue anatomy and physiology non-invasively. MRI measurements are meticulously engineered to control experimental conditions across the sample. However, residual radiofrequency (RF) field inhomogeneities are often unavoidable, leading to artefacts that degrade the diagnostic and scientific value of the images. Here we show that, paradoxically, these artefacts can be eliminated by deliberately interweaving freely varying heterogeneous RF fields into a magnetic resonance fingerprinting data-acquisition process. Observations made based on simulations are experimentally confirmed at 7 Tesla (T), and the clinical implications of this new paradigm are illustrated with in vivo measurements near an orthopaedic implant at 3T. These results show that it is possible to perform quantitative multiparametric imaging with heterogeneous RF fields, and to liberate MRI from the traditional struggle for control over the RF field uniformity. Magnetic resonance fingerprinting (MRF) requires a uniform B 1 + radiofrequency field. Here the authors present plug-n-play MRF, a technique that enables multiparametric imaging with heterogeneous B 1 + fields, and demonstrate its utility in the presence of RF distortion caused by a metallic orthopaedic implant.

The retina contains distinct types of ganglion cells, which form mosaics with cells of each type at each position of the visual field. Displaced retinal ganglion cells (dRGCs) occur with cell bodies in the inner nuclear layer (INL), and regularly placed RGCs with cell bodies in the ganglion cell layer. An example of mammalian dRGCs are M1-type intrinsically photosensitive ganglion cells (ipRGCs). Little is known, however, about their relationship with regularly placed ipRGCs. We identified mouse ipRGC types M1, M2, and M4/sONɑ by immunohistochemistry and light microscopy. Reconstruction of immunolabeled mosaics from M1 and sONɑ RGCs indicated that dRGCs tiled the retina with their regular RGC partners. Multi-electrode array recordings revealed conventional receptive fields of displaced sONɑ RGCs which fit into the mosaic of their regular counterparts. An RGC distribution analysis showed type-specific dRGC patterns which followed neither the global density distribution of all RGCs nor the local densities of corresponding cell types. The displacement of RGC bodies into the INL occurs in a type-dependent manner, where dRGCs are positioned to form complete mosaics with their regular partners. Our data suggest that dRGCs and regular RGCs serve the same functional role within their corresponding population of RGCs.

A large number of behavioral experiments have demonstrated the existence of a magnetic sense in many animal species. Further, studies with immediate gene expression markers have identified putative brain regions involved in magnetic information processing. In contrast, very little is known about the physiology of the magnetic sense and how the magnetic field is neuronally encoded. In vivo electrophysiological studies reporting neuronal correlates of the magnetic sense either have turned out to be irreproducible for lack of appropriate artifact controls or still await independent replication. Thus far, the research field of magnetoreception has little exploited the power of ex vivo physiological studies, which hold great promise for enabling stringent controls. However, tight space constraints in a recording setup and the presence of magnetizable materials in setup components and microscope objectives make it demanding to generate well-defined magnetic stimuli at the location of the biological specimen. Here, we present a solution based on a miniature vector magnetometer, a coil driver, and a calibration routine for the coil system to compensate for magnetic distortions in the setup. The magnetometer fits in common physiology recording chambers and has a sufficiently small spatial integration area to allow for probing spatial inhomogeneities. The coil-driver allows for the generation of defined non-stationary fast changing magnetic stimuli. Our ex vivo multielectrode array recordings from avian retinal ganglion cells show that artifacts induced by rapid magnetic stimulus changes can mimic the waveform of biological spikes on single electrodes. However, induction artifacts can be separated clearly from biological responses if the spatio-temporal characteristics of the artifact on multiple electrodes is taken into account. We provide the complete hardware design data and software resources for the integrated magnetic stimulation system.

Objective: The purpose of this analysis is to examine the effect of an algorithm-driven online diabetes prevention program on changes in eating habits, physical activity and wellness/productivity factors. Methods: The intervention, Alive-PD, used small-step individually tailored goal setting and other features to promote changes in diet and physical activity. A 6-month randomized controlled trial was conducted among patients from a healthcare delivery system who had confirmed prediabetes ( n =339). Change in weight and glycemic markers were measured in the clinic. Changes in physical activity, diet and wellness/productivity factors were self-reported. Mean age was 55 (s.d. 8.9) years, mean body mass index was 31 (s.d. 4.4) kg m −2 , 68% were white and 69% were male. Results: The intervention group increased fruit/vegetable consumption by 3.71 (95% confidence interval (CI) 2.73, 4.70) times per week (effect size 0.62), and decreased refined carbohydrates by 3.77 (95% CI 3.10, 4.44) times per week both significantly ( P <0.001) greater changes than in the control group. The intervention group also reported a significantly greater increase in physical activity than in the control group, effect size 0.49, P <0.001. In addition, the intervention group reported a significant increase in self-rated health, in confidence in ability to make dietary changes and in ability to accomplish tasks, and a decrease in fatigue, compared with the control group. These changes paralleled the significant treatment effects on glycemic markers and weight. Conclusions: In addition to promoting improvements in weight and glycemic markers, the Alive-PD program appears to improve eating habits and physical activity, behaviors important not just for diabetes prevention but for those with diagnosed diabetes or obesity. The improvements in wellness/productivity may derive from the diet and activity improvements, and from the satisfaction and self-efficacy of achieving goals.

Background/Objective: The rising incidence of obesity is a major public health issue worldwide. Recent human and animal studies suggest that parental diet can influence fetal development and is implicated with risk of obesity and type 2 diabetes in offspring. The hypothalamus is central to body energy homoeostasis and appetite by controlling endocrine signals. We hypothesise that offspring susceptibility to obesity is programmed in the hypothalamus in utero and mediated by changes to DNA methylation, which persist to adulthood. We investigated hypothalamic genome-wide DNA methylation in Psammomys obesus diet during pregnancy to the offspring’s risk of obesity. Methods: Using methyl-CpG binding domain capture and deep sequencing (MBD-seq), we examined the hypothalamus of offspring exposed to a low-fat diet and standard chow diet during the gestation and lactation period. Results: Offspring exposed to a low-fat parental diet were more obese and had increased circulating insulin and glucose levels. Methylome profiling identified 1447 genomic regions of differential methylation between offspring of parents fed a low-fat diet compared with parents on standard chow diet. Pathway analysis shows novel DNA methylation changes of hypothalamic genes associated with neurological function, nutrient sensing, appetite and energy balance. Differential DNA methylation corresponded to changes in hypothalamic gene expression of Tas1r1 and Abcc8 in the offspring exposed to low-fat parental diet. Conclusion: Subject to parental low-fat diet, we observe DNA methylation changes of genes associated with obesity in offspring.

Objectives To compare dynamic magnetic resonance imaging (MRI) with videofluoroscopy (VFS) regarding image quality and assessment of gap size between soft palate (SP) and posterior pharyngeal wall (PPW) in children and adolescents following surgical correction of velopharyngeal dysfunction (VPD). Methods Twenty-one patients undergoing unenhanced 3-T MRI and contrast-enhanced VFS were included in this IRB-approved prospective study. The MRI scan protocol comprised refocused gradient-echo sequences in transverse and sagittal planes during speech, with TE 1.97 ms, TR 3.95 ms, flip angle 8°, matrix size 128 × 128, and 5-mm slice thickness. Radial k-space sampling and sliding window reconstruction were used to achieve an image acquisition rate of 28 frames per second (fps). VFS with 30 fps was similarly performed in both planes. Closure of the velopharyngeal port during phonation was evaluated by two experienced radiologists. Results Eleven (52.4%) patients displayed a complete closure, whereas ten (47.6%) patients showed a post-operative gap during speech. VFS and MRI equally identified the cases with persistent or recurrent VPD. Differences in SP-PPW distance between VFS (3.9 ± 1.6 mm) and MRI (4.1 ± 1.5 mm) were not statistically significant ( p  = 0.5). The subjective overall image quality of MRI was rated inferior ( p  < 0.001) compared with VFS, with almost perfect inter-rater agreement ( κ  = 0.90). The presence of susceptibility artifacts did not limit anatomical measurements. Conclusion Dynamic MRI is equally reliable as VFS to assess persistent or recurrent inadequate velum closure in patients following surgical treatment of VPD. Key Points • Unenhanced 3-T dynamic MRI and contrast-enhanced videofluoroscopy are equally useful for the identification of patients with incomplete velopharyngeal closure during speech . • MRI using refocused gradient-echo acquisition with radial k-space sampling and sliding window reconstruction generates diagnostic images with 28 frames per second . • MRI can offer a radiation-free alternative to currently established videofluoroscopy for young patients.

Gaseous detectors based on large-size GEM-foils are planned to be used for a variety of upgrades and new experiments using high-rate and high-intensity particle beams. An excellent quality control of GEM-foils is a mandatory prerequisite to select the best foils for the assembly of a GEM detector. The high voltage stability of the foils is here of uppermost importance. In particular discharges that occur at the same position need to be detected. A spark detection system has been developed to automatically detect and record the time and position of sparks. The system is based on a commercial web camera installed in a housing for the tests and a custom-made, LabVIEW-based software for control and operation. An automatic Spark-Detection System for GEM foils was designed, built and characterized. It is able to detect and record discharges in large-size GEM foils during the quality control procedure. The spark detection e ciency was estimated to be higher than 97 %, the position resolution was determined to be approximately 0.5 mm. With this system, the characterization of GEM foils can be standardized to a much greater degree than before.

Dengue viruses co-circulate as four serologically distinct viruses (DENV1–4) that commonly infect individuals sequentially. Current DENV candidate vaccines incorporate the entire virion envelope E protein (E) ectodomain thereby stimulating both DENV serotype-specific and cross-reactive antibodies. Because the latter may enhance naturally acquired infection, such vaccine formulations must be tetravalent. We evaluated the neutralizing and enhancing antibody response to E domain III (dIII) proteins, in which serotype-specific neutralizing determinants are concentrated. Mice immunized with insect cell-secreted recombinant DENV-dIII proteins individually, and in tetravalent combination, produced serotype-specific IgG1 neutralizing antibodies that nevertheless exhibited measurable DENV enhancing activity in FcγR-bearing cells. Vaccine strategies directed to DENV-dIII-targeted neutralizing antibody production remain attractive but will likely require further modifications to induce safe, protective immunity.

Hepatocellular carcinoma (HCC) is the fifth most common cancer, but the third leading cause of cancer death, in the world, with more than 500 000 fatalities annually. The major etiology of HCC/liver cancer in people is hepatitis B virus (HBV), followed by hepatitis C virus infection (HCV), although nonviral causes also play a role in a minority of cases. Recent molecular studies confirm what was suspected: that HCC tissue from different individuals have many phenotypic differences. However, there are clearly features that unify HCC occurring in a background of viral hepatitis B and C. HCC due to HBV and HCV may be an indirect result of enhanced hepatocyte turnover that occurs in an effort to replace infected cells that have been immunologically attacked. Viral functions may also play a more direct role in mediating oncogenesis. This review considers the molecular and cellular mechanisms involved in primary hepatocellular carcinoma, using a viral perspective.