MR Elastography Analysis of Glioma Stiffness and IDH1-Mutation Status.

BACKGROUND AND PURPOSE: Our aim was to noninvasively evaluate gliomas with MR elastography to characterize the relationship of tumor stiffness with tumor grade and mutations in the isocitrate dehydrogenase 1 (IDH1) gene. MATERIALS AND METHODS: Tumor stiffness properties were prospectively quantified in 18 patients (mean age, 42 years; 6 women) with histologically proved gliomas using MR elastography from 2014 to 2016. Images were acquired on a 3T MR imaging unit with a vibration frequency of 60 Hz. Tumor stiffness was compared with unaffected contralateral white matter, across tumor grade, and by IDH1-mutation status. The performance of the use of tumor stiffness to predict tumor grade and IDH1 mutation was evaluated with the Wilcoxon rank sum, 1-way ANOVA, and Tukey-Kramer tests. RESULTS: Gliomas were softer than healthy brain parenchyma, 2.2 kPa compared with 3.3 kPa (P < .001), with grade IV tumors softer than grade II. Tumors with an IDH1 mutation were significantly stiffer than those with wild type IDH1, 2.5 kPa versus 1.6 kPa, respectively (P = .007). CONCLUSIONS: MR elastography demonstrated that not only were gliomas softer than normal brain but the degree of softening was directly correlated with tumor grade and IDH1-mutation status. Noninvasive determination of tumor grade and IDH1 mutation may result in improved stratification of patients for different treatment options and the evaluation of novel therapeutics. This work reports on the emerging field of "mechanogenomics": the identification of genetic features such as IDH1 mutation using intrinsic biomechanical information.

An altered endometrial CD8 tissue resident memory T cell population in recurrent miscarriage.

When trying to conceive 1% of couples have recurrent miscarriages, defined as three or more consecutive pregnancy losses. This is not accounted for by the known incidence of chromosomal aneuploidy in miscarriage, and it has been suggested that there is an immunological aetiology. The endometrial mucosa is populated by a variety of immune cells which in addition to providing host pathogen immunity must facilitate pregnancy. Here we characterise the endometrial CD8-T cell population during the embryonic window of implantation and find that the majority of cells are tissue resident memory T cells with high levels of CD69 and CD103 expression, proteins that prevent cells egress. We demonstrate that unexplained recurrent miscarriage is associated with significantly decreased expression of the T-cell co-receptor CD8 and tissue residency marker CD69. These cells differ from those found in control women, with less expression of CD127 indicating a lack of homeostatic cell control through IL-7 signalling. Nevertheless this population is resident in the endometrium of women who have RM, more than three months after the last miscarriage, indicating that the memory CD8-T cell population is altered in RM patients. This is the first evidence of a differing pre-pregnancy phenotype in endometrial immune cells in RM.

Distortion product otoacoustic emissions in geriatric dogs.

Recordings of distortion product otoacoustic emissions (DPOAE) were taken from 28 geriatric dogs aged 12.2 ± 2.2 years and 15 control dogs aged 5.9 ± 3.0 years (mean ± standard deviation) to demonstrate frequency-specific changes in cochlear responses. Recordings were performed for primary frequencies of 2-12 kHz in 2 kHz increments. Brainstem auditory evoked response (BAER) recordings were also made from geriatric dogs for comparison with DPOAE responses. Significant decreases in DPOAE response amplitudes were observed at frequencies of 6-12 kHz in geriatric dogs compared to control dogs, reflecting loss of cochlear outer hair cells along the length of the cochlea. Significant decreases in response amplitudes were not seen at frequencies of 2 or 4 kHz. Decreases in BAER response amplitudes subjectively paralleled the depressed DPOAE amplitudes. No significant linear regression relationships were found for DPOAE response amplitude vs. age despite the progressive nature of age-related hearing loss. The reductions in response at all frequencies starting at the age where dogs are considered geriatric indicate that age-related hearing loss begins earlier in the life span. DPOAE recordings provide a means to assess cochlear function across different portions of the auditory spectrum for assessing hearing loss associated with aging, and potentially for losses from other causes of decreased auditory function.

Low-Mach-number turbulence in interstellar gas revealed by radio polarization gradients.

The interstellar medium of the Milky Way is multiphase, magnetized and turbulent. Turbulence in the interstellar medium produces a global cascade of random gas motions, spanning scales ranging from 100 parsecs to 1,000 kilometres (ref. 4). Fundamental parameters of interstellar turbulence such as the sonic Mach number (the speed of sound) have been difficult to determine, because observations have lacked the sensitivity and resolution to image the small-scale structure associated with turbulent motion. Observations of linear polarization and Faraday rotation in radio emission from the Milky Way have identified unusual polarized structures that often have no counterparts in the total radiation intensity or at other wavelengths, and whose physical significance has been unclear. Here we report that the gradient of the Stokes vector (Q, U), where Q and U are parameters describing the polarization state of radiation, provides an image of magnetized turbulence in diffuse, ionized gas, manifested as a complex filamentary web of discontinuities in gas density and magnetic field. Through comparison with simulations, we demonstrate that turbulence in the warm, ionized medium has a relatively low sonic Mach number, M(s) ≲ 2. The development of statistical tools for the analysis of polarization gradients will allow accurate determinations of the Mach number, Reynolds number and magnetic field strength in interstellar turbulence over a wide range of conditions.

Calculation of shear stiffness in noise dominated magnetic resonance elastography data based on principal frequency estimation.

Magnetic resonance elastography (MRE) is a non-invasive phase-contrast-based method for quantifying the shear stiffness of biological tissues. Synchronous application of a shear wave source and motion encoding gradient waveforms within the MRE pulse sequence enable visualization of the propagating shear wave throughout the medium under investigation. Encoded shear wave-induced displacements are then processed to calculate the local shear stiffness of each voxel. An important consideration in local shear stiffness estimates is that the algorithms employed typically calculate shear stiffness using relatively high signal-to-noise ratio (SNR) MRE images and have difficulties at an extremely low SNR. A new method of estimating shear stiffness based on the principal spatial frequency of the shear wave displacement map is presented. Finite element simulations were performed to assess the relative insensitivity of this approach to decreases in SNR. Additionally, ex vivo experiments were conducted on normal rat lungs to assess the robustness of this approach in low SNR biological tissue. Simulation and experimental results indicate that calculation of shear stiffness by the principal frequency method is less sensitive to extremely low SNR than previously reported MRE inversion methods but at the expense of loss of spatial information within the region of interest from which the principal frequency estimate is derived.

Glucose oscillations, more than constant high glucose, induce p53 activation and a metabolic memory in human endothelial cells.

AIMS/HYPOTHESIS: Damage persists in HUVECs exposed to a constant high glucose concentration long after glucose normalisation, a phenomenon termed 'metabolic memory'. Evaluation of the effects of exposure of HUVECs to oscillating high glucose on the induction of markers of oxidative stress and DNA damage (phospho-γ-histone H2AX and PKCδ) and onset of metabolic memory, and the possible role of the tumour suppressor transcriptional factor p53 is of pivotal interest. METHODS: HUVECs were incubated for 3 weeks in 5 or 25 mmol/l glucose or oscillating glucose (24 h in 5 mmol/l glucose followed by 24 h in 25 mmol/l glucose) or for 1 week in constant 5 mmol/l glucose after being exposed for 2 weeks to continuous 25 mmol/l high glucose or oscillating glucose. Transcriptional activity of p53 was also evaluated in the first 24 h after high glucose exposure. RESULTS: High constant glucose upregulated phospho-γ-histone H2AX and protein kinase C (PKC)δ compared with control. Oscillating glucose was even more effective than both normal and constant high glucose. Both constant and oscillating glucose resulted in a memory effect, which was more pronounced in the oscillating condition. Transcriptional activity of p53 peaked 6 h after glucose exposure, showing a predicted oscillatory behaviour. CONCLUSIONS/INTERPRETATION: Exposure to oscillating glucose was more deleterious than constant high glucose and induced a metabolic memory after glucose normalisation. Hyperactivation of p53 during glucose oscillation might be due to the absence of consistent feedback inhibition during each glucose spike and might account for the worse outcome of this condition.

Analgesic Efficacy of Pfannenstiel Incision Infiltration with Ropivacaine 7.5 mg/mL for Caesarean Section.

Background. Pain after Caesarean delivery is partly related to Pfannenstiel incision, which can be infiltrated with local anaesthetic solutions. Methods. A double- blind randomized control trial was designed to assess the analgesic efficacy of 7.5 mg/mL ropivacaine solution compared to control group, in two groups of one hundred and forty four parturients for each group, who underwent Caesarean section under spinal anaesthesia: group R (ropivacaine group) and group C (control group). All parturients also received spinal sufentanil (2.5 mug). Results. Ropivacaine infiltration in the Pfannenstiel incision for Caesarean delivery before wound closure leads to a reduction of 30% in the overall consumption of analgesics (348 550 mg for group R versus 504 426 mg for group C with P < .05), especially opioids in the first 24 hours, but also significantly increases the time interval until the first request for an analgesic (4 h 20 min +/- 2 h 26 for group R versus 2 h 42 +/- 1 h 30 for group C). The P values for the two groups were: P < .0001 for paracetamol, P < .0001 for ketoprofen and P for nalbuphine which was the most significant. There is no significant difference in the threshold of VAS in the two series. Conclusion. This technique can contribute towards a programme of early rehabilitation in sectioned mothers, with earlier discharge from the post-labour suite.

Dydrogesterone and norethisterone regulate expression of lipoprotein lipase and hormone-sensitive lipase in human subcutaneous abdominal adipocytes.

AIM: In premenopausal women, hyperandrogenicity is associated with central obesity and an increased cardiovascular risk. The aim of this study was to investigate the effects of dydrogesterone (DYD) (a non-androgenic progestogen) and norethisterone (NET) (an androgenic progestogen) on lipoprotein lipase (LPL), hormone-sensitive lipase (HSL) and glycerol release in adipocytes isolated from subcutaneous abdominal adipose tissue. METHODS: Adipose tissue was obtained from 12 non-diabetic women, mean age 51 years (range 37-78) and mean body mass index 25.4 kg/m(2) (range 20.3-26.4). Adipocytes were treated with increasing doses of DYD and NET for 48 h prior to protein extraction. Effects on lipogenesis and lipolysis were assessed using western blotting to determine the expression of key enzymes, LPL (56 kDa) and HSL (84 kDa) respectively. Measurement of glycerol release into the medium provided an assessment of lipolytic activity. RESULTS: Expression of LPL was increased by DYD and NET (mean protein expression relative to control +/- s.e.), with greatest effect at 10(-8) M for DYD: 2.32 +/- 0.51 (p < 0.01) and 10(-8) M for NET: 2.06 +/- 0.19 (p < 0.01). In contrast, HSL expression was reduced by all concentrations of DYD, with maximal effect at 10(-9) M : 0.49 +/- 0.02 (p < 0.001). NET reduced HSL expression at all concentrations from 10(-9) M : 0.62 +/- 0.06 (p < 0.001) to 10(-7) M : 0.69 +/- 0.08 (p < 0.001). Glycerol measurements supported the HSL expression studies although they were not statistically significant (p > 0.05). CONCLUSIONS: DYD and NET significantly increased LPL expression relative to control, while significantly reducing HSL expression. At the concentrations studied, similar effects were observed with the androgenic NET and the non-androgenic DYD despite differing effects on the lipid profile when taken orally in combination with oestrogen. Further work examining the effects of different progestogens on body fat distribution may enable progestogen use to be tailored to maximize benefits and minimize potential harm.

Magnetic resonance elastography of the lung: technical feasibility.

Magnetic resonance elastography (MRE) is a phase-contrast technique that can spatially map shear stiffness within tissue-like materials. To date, however, MRE of the lung has been too technically challenging-primarily because of signal-to-noise ratio (SNR) limitations and phase instability. We describe an approach in which shear wave propagation is not encoded into the phase of the MR signal of a material, but rather from the signal arising from a polarized noble gas encapsulated within. To determine the feasibility of the approach, three experiments were performed. First, to establish whether shear wave propagation within lung parenchyma can be visualized with phase-contrast MR techniques, MRE was performed on excised porcine lungs inflated with room air. Second, a phantom consisting of open-cell foam filled with thermally polarized (3)He gas was imaged with MRE to determine whether shear wave propagation can be encoded by the gas. Third, preliminary evidence of the feasibility of MRE in vivo was obtained by using a longitudinal driver on the chest of a normal volunteer to generate shear waves in the lung. The results suggest that MRE in combination with hyperpolarized noble gases is potentially useful for noninvasively assessing the regional elastic properties of lung parenchyma, and merits further investigation.

MR guided focused ultrasound: technical acceptance measures for a clinical system.

Magnetic resonance (MR) guided focused ultrasound (MRgFUS) is a hybrid technique which offers efficient and safe focused ultrasound (FUS) treatments of uterine fibroids under MR guidance and monitoring. As a therapy device, MRgFUS requires systematic testing over a wide range of operational parameters prior to use in the clinical environment. We present technical acceptance tests and data for the first clinical MRgFUS system, ExAblate 2000 (InSightec Inc., Haifa, Israel), that has been FDA approved for treating uterine fibroids. These tests characterize MRgFUS by employing MR temperature measurements in tissue mimicking phantoms. The coronal scan plane is empirically demonstrated to be most reliable for measuring temperature elevations resulting from high intensity ultrasound (US) pulses ('sonications') and shows high sensitivity to changes in sonication parameters. Temperatures measured in the coronal plane were used as a measure of US energy deposited within the focal spot for a range of sonication parameters used in clinical treatments: spot type, spot length, output power, sonication duration, US frequency, and depth of sonication. In addition, MR images acquired during sonications were used to measure effective diameters and lengths of available sonication spot types and lengths. At a constant 60 W output power, the effective spot type diameters were measured to vary between 4.7 +/- 0.3 mm and 6.6 +/- 0.4 mm; treatment temperatures were found to decrease with increasing spot diameter. Prescribing different spot lengths was found to have no effect on the measured length or on measured temperatures. Tests of MRgFUS positioning accuracy determined errors in the direction parallel to the propagation of the US beam to be significantly greater than those in the perpendicular direction; most sonication spots were erroneously positioned towards the FUS transducer. The tests reported here have been demonstrated to be sufficiently sensitive to detect water leakage inside the FUS transducer. The data presented could be used for comparison by those conducting acceptance tests on other clinical MRgFUS systems.

An expanding radio nebula produced by a giant flare from the magnetar SGR 1806-20.

Soft gamma-ray repeaters (SGRs) are 'magnetars', a small class of slowly spinning neutron stars with extreme surface magnetic fields, B approximately 10(15) gauss (refs 1 , 2 -3). On 27 December 2004, a giant flare was detected from the magnetar SGR 1806-20 (ref. 2), only the third such event recorded. This burst of energy was detected by a variety of instruments and even caused an ionospheric disturbance in the Earth's upper atmosphere that was recorded around the globe. Here we report the detection of a fading radio afterglow produced by this outburst, with a luminosity 500 times larger than the only other detection of a similar source. From day 6 to day 19 after the flare from SGR 1806-20, a resolved, linearly polarized, radio nebula was seen, expanding at approximately a quarter of the speed of light. To create this nebula, at least 4 x 10(43) ergs of energy must have been emitted by the giant flare in the form of magnetic fields and relativistic particles.

The epidemiology of drowning worldwide.

The purpose of this analysis was to quantify the magnitude of death and disability from drowning and near-drowning worldwide and to provide epidemiological data on which to base prevention efforts. All data are from the Global Burden of Disease 2000 (Version 1) estimates in which deaths and disabilities are based on the WHO International Classification of Diseases. Extrapolations were made by age, sex, and WHO region. The six WHO regions of the world were further divided into high-income, and low- and middle-income based on the 1998 World Development indicators. According to the GBD 2000 data, an estimated 449,000 people drowned worldwide (7.4 per 100,000 population) and a further 1.3 million Disability Adjusted Life Years (DALYs) were lost as a result of premature death or disability from drowning. 97% of drownings occurred in low- and middle-income countries. Although 38% of drownings occurred in the Western Pacific Region, Africa had the highest drowning mortality rate (13.1 per 100,000 population). Males had higher drowning mortality rates than females for all ages and in all regions. Children under the age of 5 years had the highest drowning mortality rate for both sexes in all of the WHO regions except for Africa, where children aged 5 to 14 years had the highest mortality rate. Worldwide, for children under the age of 15 years, drowning accounted for a higher mortality rate than any other cause of injury. Drowning is a significant problem worldwide particularly for children under the age of 15 years. Low- and middle-income countries have the highest rates of drowning and account for more than 90% of such fatalities. Primary prevention efforts should thus be focused on these countries where many children who cannot swim drown in large bodies of water.

Review of evaluations of educational approaches to promote safe storage of firearms.

OBJECTIVE: To systematically review evaluation studies of educational interventions promoting safe firearm storage. METHODS: Medline, ERIC, PsycINFO, Criminal Justice Periodicals Index, Cumulative Index of Nursing and Allied Health Literature, and Sociofile were searched. The references from each potentially eligible study were checked, and experts in the field were contacted for additional reports. In addition, an internet search was performed to identify programs not published in the conventional literature. Sources relevant to safe firearm storage promotion were selected and evaluated. RESULTS: Seven studies met inclusion criteria: adult subjects, program description was included, and firearm storage outcomes were measured. One was a randomized controlled trial and the other six were one group pre-test and/or post-test. The studies were classified into the following categories based on the intervention strategies used: (1). counseling and firearm safety materials (n=3); (2). counseling/educational message (n=3); and (3). firearm safety materials distribution (n=1). The outcomes were safe firearms storage (firearms locked up and unloaded or removal from home) after intervention. Four studies, three using counseling and materials distribution, reported improved storage after the interventions. CONCLUSIONS: It is not yet clear what types of interventions, or which specific intervention components, prompt gun owners to securely store their weapons. Increased understanding of gun storage behaviors and stronger evaluation designs will aid further understanding of this important issue.

A model nursing computer resource center.

Nursing graduates are required to demonstrate computer technology skills and critical reflective thinking skills in the workplace. The authors discuss a model computer resource center that enhances the acquisition of these requisite skills by students in both an associate degree and vocational nursing program. The computer resource center maximizes student learning and promotes faculty effectiveness and efficiency by a "full-service" approach to computerized testing, information technology instruction, online research, and interactive computer program practice.

A role for N-WASP in invasin-promoted internalisation.

Phagocytosis of Yersinia pseudotuberculosis occurs through interaction of the bacterial protein invasin with beta1-integrins. Here we report that N-WASP plays a role in internalisation of an invasin-expressing, avirulent strain of Y. pseudotuberculosis. Ectopic expression of N-WASP mutants, which affect recruitment of the Arp2/3 complex to the phagosome, reduces uptake of Yersinia. In addition, expression of the Cdc42/Rac-binding (CRIB) region of N-WASP has an inhibitory effect on uptake. Using GFP-tagged Rho GTPase mutants, we provide evidence that Rac1, but not Cdc42, is important for internalisation. Furthermore, activated Rac1 rescues Toxin B, CRIB and Src family kinase inhibitor PP2-mediated impairment of uptake. Our observations indicate that invasin-mediated phagocytosis occurs via a Src and WASP family-dependent mechanism(s), involving the Arp2/3 complex and Rac, but does not require Cdc42.

Clinical use of electronic portal imaging: report of AAPM Radiation Therapy Committee Task Group 58.

AAPM Task Group 58 was created to provide materials to help the medical physicist and colleagues succeed in the clinical implementation of electronic portal imaging devices (EPIDs) in radiation oncology. This complex technology has matured over the past decade and is capable of being integrated into routine practice. However, the difficulties encountered during the specification, installation, and implementation process can be overwhelming. TG58 was charged with providing sufficient information to allow the users to overcome these difficulties and put EPIDs into routine clinical practice. In answering the charge, this report provides; comprehensive information about the physics and technology of currently available EPID systems; a detailed discussion of the steps required for successful clinical implementation, based on accumulated experience; a review of software tools available and clinical use protocols to enhance EPID utilization; and specific quality assurance requirements for initial and continuing clinical use of the systems. Specific recommendations are summarized to assist the reader with successful implementation and continuing use of an EPID.

A note on hair whorl position and cattle temperament in the auction ring.

The objective of this study was to further describe the relationships between facial hair whorls and temperament in cattle. Cattle (n=1636) from six commercial cattle auctions in Colorado and Texas were observed. Whorl location was classified according to lateral position (left, right, or middle) and height (high: above the top of the eye, middle: at eye level, low: below the bottom of the eye). A 4-point temperament score was used to rate each animal while it was in the auction ring. Cattle with a score of 1 remained calm and stood still or walked around, and those with a score of 4 were highly agitated and hit the ring fence, walls, partitions, or people with its head. The cattle observed were 75% Bos taurus beef breeds, 21% Holstein dairy cattle, 3% Bos indicus beef breeds, and 1% non-Holstein dairy breeds. Ten percent of cattle surveyed had no facial hair whorl, while 86% had a single spiral hair whorl, of which 47% had middle-middle whorl placement. Animals with a high whorl position or no hair whorl had higher temperament scores (P=0.01). Cattle with low whorls were more likely to have greater lateral displacement of whorls off of the centerline than cattle with high or middle whorls (P<0.01). Abnormally shaped whorls were more common on cattle with low whorls (P<0.01) and on cattle with lateral whorls located off of the centerline (P<0.01). Cattle with hair whorls on the centerline had more variable temperament scores (P=0.04). Beef cattle had more abnormal whorls than Holsteins (P<0.01). Temperament scores showed that Holsteins were calmer than beef cattle (P<0.01). Facial hair whorls in cattle may be a useful management tool in assessing which animals may become disturbed in novel environments.

Autocorrection of three-dimensional time-of-flight MR angiography of the Circle of Willis.

OBJECTIVE: The purpose of this study was to investigate the efficacy of a retrospective adaptive motion correction technique known as autocorrection for reducing motion-induced artifacts in high-resolution three-dimensional time-of-flight MR angiography of the circle of Willis. MATERIALS AND METHODS: Ten consecutive volunteers were imaged with an unenhanced gradient-recalled echo three-dimensional time-of-flight MR angiography sequence of the circle of Willis. Each volunteer was asked to rotate approximately 2 degrees after completion of one third and one half of the acquisition in the axial, sagittal, and oblique planes (45 degrees to the axial and sagittal planes). A single static data set was also acquired for each volunteer. Unprocessed and autocorrected maximum-intensity-projection images were reviewed as blinded image pairs by six radiologists and were compared on a five-point image quality scale. RESULTS: Mean improvement in image quality after autocorrection was 1.4 (p < 0.0001), 1.1 (p < 0.0001), and 0.2 (p = 0.003) observer points (maximum value, 2.0), respectively, for examinations corrupted by motion in the axial, oblique, and sagittal planes. All three axes had statistically significant improvement in image quality compared with the uncorrected images. Changes in image quality after the application of the autocorrection algorithm to static angiogram data were not statistically significant (mean change in score = -0.13 points; p = 0.29). CONCLUSION: Autocorrection can reduce artifacts in motion-corrupted MR angiography of the circle of Willis without distorting motion-free examinations.

Care Groups: a model to mentor novice nursing students.

To lessen anxiety and promote the acquisition of basic skills and professional values in novice students, faculty incorporated special groups, called Care Groups, in the curriculum. Care Groups promote caring relationships. They help students to succeed by decreasing their apprehension and anxiety when demonstrating basic nursing skills in a laboratory environment. The authors discuss the structure and process of Care Groups and the faculty's role as mentor.