Systematic Characterization of the Clinical and Pathological Features of Schwannomas Harboring SH3PXD2A::HTRA1 Fusion.

The understanding of schwannoma tumorigenesis has been reshaped by the recent identification of SH3PXD2A::HTRA1 fusion in 10% of intracranial/spinal schwannomas. Nonetheless, pathologic features of schwannomas harboring this fusion, as well as its prevalence outside intracranial/spinal locations, have not been characterized. We screened 215 consecutive schwannomas for their clinicopathologic characteristics and fusion status using reverse-transcriptase polymerase chain reaction (RT-PCR). Among 29 (13.5%) fusion-positive schwannomas, the most prevalent location was peripheral somatic tissue (30.7%, 19/62), followed by spinal/paraspinal (18.4%, 7/38), body cavity/deep structures (10%, 2/20), intracranial (1.3%, 1/75), and viscera (0/13). All 8 cellular, 4 microcystic/reticular, and 3 epithelioid schwannomas were fusion-negative, as were 41/42 nonschwannomatous peripheral nerve sheath tumors. Remarkably, a distinct 'serpentine' palisading pattern, comprising ovoid/plump cells shorter than usual schwannian cells in a hyalinized stroma, was identified in most fusion-positive cases and the schwannomatous component of the only fusion-positive malignant peripheral nerve sheath tumor. To validate this finding, 60 additional cases were collected, including 36 with (≥10% arbitrarily) and 24 without appreciable serpentine histology, of which 29 (80.6%) and 2 (8.3%) harbored the fusion, respectively. With percentages of 'serpentine' areas scored, 10% was determined as the optimal practical cut-off to predict the fusion status (sensitivity, 0.950; specificity, 0.943). Fusion positivity was significantly associated with serpentine histology, smaller tumors, younger patients, and peripheral somatic tissue, while multivariate logistic linear regression analysis only identified serpentine histology and location as independent fusion-predicting factors. RNA in situ hybridization successfully detected the fusion junction, highly concordant with RT-PCR results. Gene expression profiling on 18 schwannomas demonstrated segregation largely consistent with fusion status. Fusion-positive cases expressed significantly higher HTRA1 mRNA abundance, perhaps exploitable as a biomarker. In summary, we systematically characterize a series of 60 SH3PXD2A::HTRA1 fusion-positive schwannomas, showing their distinctive morphology and location-specific prevalence for the first time.

Gender Differences in the Prevalence of Metabolic Syndrome Among Taiwanese Air Force Personnel: A Population-Based Study.

BACKGROUND: Authors of several studies have reported differences in the prevalence of metabolic syndrome (MetS) between men and women. However, information is lacking on gender difference among military personnel. OBJECTIVE: The aim of this study was to examine the prevalence of MetS and its component abnormalities among Taiwanese Air Force personnel by gender and age groups. METHODS: A population-based study was conducted including 14 872 Taiwanese Air Force personnel. Data were retrieved from the military's Health Management Information System. Analyses were performed using Student t test, χ test, and linear-by-linear χ test. Statistical significance was defined as P < .05. RESULTS: The MetS prevalence was 14.0% (15.1% in men and 5.3% in women). Metabolic syndrome was associated with age for both men and women (both Ptrend < .001), with a greater prevalence of MetS in men aged 18 to 44 years than in women, but not in the age group of 45 years or older. In men, MetS was most prevalent in those with increased waist circumference (78.2%), followed by those with elevated blood pressure (75.6%). By contrast, in women, it was most prevalent in those with increased waist circumference (86.5%), followed by those with reduced high-density lipoprotein cholesterol (84.3%). CONCLUSIONS: Our findings suggest that military nurses and other health providers should consider the gender- and age-based MetS prevalence trend among Taiwanese Air Force personnel when designing interventions to identify vulnerable subgroups at a high risk of MetS. Health management programs should be adapted to minimize metabolic risks.

A laser frequency comb that enables radial velocity measurements with a precision of 1 cm s(-1).

Searches for extrasolar planets using the periodic Doppler shift of stellar spectral lines have recently achieved a precision of 60 cm s(-1) (ref. 1), which is sufficient to find a 5-Earth-mass planet in a Mercury-like orbit around a Sun-like star. To find a 1-Earth-mass planet in an Earth-like orbit, a precision of approximately 5 cm s(-1) is necessary. The combination of a laser frequency comb with a Fabry-Pérot filtering cavity has been suggested as a promising approach to achieve such Doppler shift resolution via improved spectrograph wavelength calibration, with recent encouraging results. Here we report the fabrication of such a filtered laser comb with up to 40-GHz (approximately 1-A) line spacing, generated from a 1-GHz repetition-rate source, without compromising long-term stability, reproducibility or spectral resolution. This wide-line-spacing comb, or 'astro-comb', is well matched to the resolving power of high-resolution astrophysical spectrographs. The astro-comb should allow a precision as high as 1 cm s(-1) in astronomical radial velocity measurements.

Optimization of filtering schemes for broadband astro-combs.

To realize a broadband, large-line-spacing astro-comb, suitable for wavelength calibration of astrophysical spectrographs, from a narrowband, femtosecond laser frequency comb ("source-comb"), one must integrate the source-comb with three additional components: (1) one or more filter cavities to multiply the source-comb's repetition rate and thus line spacing; (2) power amplifiers to boost the power of pulses from the filtered comb; and (3) highly nonlinear optical fiber to spectrally broaden the filtered and amplified narrowband frequency comb. In this paper we analyze the interplay of Fabry-Perot (FP) filter cavities with power amplifiers and nonlinear broadening fiber in the design of astro-combs optimized for radial-velocity (RV) calibration accuracy. We present analytic and numeric models and use them to evaluate a variety of FP filtering schemes (labeled as identical, co-prime, fraction-prime, and conjugate cavities), coupled to chirped-pulse amplification (CPA). We find that even a small nonlinear phase can reduce suppression of filtered comb lines, and increase RV error for spectrograph calibration. In general, filtering with two cavities prior to the CPA fiber amplifier outperforms an amplifier placed between the two cavities. In particular, filtering with conjugate cavities is able to provide <1 cm/s RV calibration error with >300 nm wavelength coverage. Such superior performance will facilitate the search for and characterization of Earth-like exoplanets, which requires <10 cm/s RV calibration error.

Calibration of an astrophysical spectrograph below 1 m/s using a laser frequency comb.

We deployed two wavelength calibrators based on laser frequency combs ("astro-combs") at an astronomical telescope. One astro-comb operated over a 100 nm band in the deep red (∼ 800 nm) and a second operated over a 20 nm band in the blue (∼ 400 nm). We used these red and blue astro-combs to calibrate a high-resolution astrophysical spectrograph integrated with a 1.5 m telescope, and demonstrated calibration precision and stability sufficient to enable detection of changes in stellar radial velocity < 1 m/s.

Conjugate Fabry-Perot cavity pair for improved astro-comb accuracy.

We propose a new astro-comb mode-filtering scheme composed of two Fabry-Perot cavities (coined "conjugate Fabry-Perot cavity pair"). Simulations indicate that this new filtering scheme makes the accuracy of astro-comb spectral lines more robust against systematic errors induced by nonlinear processes associated with power-amplifying and spectral-broadening optical fibers.

Machine Learning Based on Morphological Features Enables Classification of Primary Intestinal T-Cell Lymphomas.

The aim of this study was to investigate the feasibility of using machine learning techniques based on morphological features in classifying two subtypes of primary intestinal T-cell lymphomas (PITLs) defined according to the WHO criteria: monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) versus intestinal T-cell lymphoma, not otherwise specified (ITCL-NOS), which is considered a major challenge for pathological diagnosis. A total of 40 histopathological whole-slide images (WSIs) from 40 surgically resected PITL cases were used as the dataset for model training and testing. A deep neural network was trained to detect and segment the nuclei of lymphocytes. Quantitative nuclear morphometrics were further computed from these predicted contours. A decision-tree-based machine learning algorithm, XGBoost, was then trained to classify PITL cases into two disease subtypes using these nuclear morphometric features. The deep neural network achieved an average precision of 0.881 in the cell segmentation work. In terms of classifying MEITL versus ITCL-NOS, the XGBoost model achieved an area under receiver operating characteristic curve (AUC) of 0.966. Our research demonstrated an accurate, human-interpretable approach to using machine learning algorithms for reducing the high dimensionality of image features and classifying T cell lymphomas that present challenges in morphologic diagnosis. The quantitative nuclear morphometric features may lead to further discoveries concerning the relationship between cellular phenotype and disease status.

Toward a broadband astro-comb: effects of nonlinear spectral broadening in optical fibers.

We propose and analyze a new approach to generate a broadband astro-comb by spectral broadening of a narrowband astro-comb inside a highly nonlinear optical fiber. Numerical modeling shows that cascaded four-wave-mixing dramatically degrades the input comb's side-mode suppression and causes side-mode amplitude asymmetry. These two detrimental effects can systematically shift the center-of-gravity of astro-comb spectral lines as measured by an astrophysical spectrograph with resolution approximately 100,000; and thus lead to wavelength calibration inaccuracy and instability. Our simulations indicate that this performance penalty, as a result of nonlinear spectral broadening, can be compensated by using a filtering cavity configured for double-pass. As an explicit example, we present a design based on an Yb-fiber source comb (with 1 GHz repetition rate) that is filtered by double-passing through a low finesse cavity (finesse = 208), and subsequent spectrally broadened in a 2-cm, SF6-glass photonic crystal fiber. Spanning more than 300 nm with 16 GHz line spacing, the resulting astro-comb is predicted to provide 1 cm/s (approximately 10 kHz) radial velocity calibration accuracy for an astrophysical spectrograph. Such extreme performance will be necessary for the search for and characterization of Earth-like extra-solar planets, and in direct measurements of the change of the rate of cosmological expansion.

Broadband dispersion-free optical cavities based on zero group delay dispersion mirror sets.

A broadband dispersion-free optical cavity using a zero group delay dispersion (zero-GDD) mirror set is demonstrated. In general zero-GDD mirror sets consist of two or more mirrors with opposite group delay dispersion (GDD), that when used together, form an optical cavity with vanishing dispersion over an enhanced bandwidth in comparison with traditional low GDD mirrors. More specifically, in this paper, we show a realization of such a two-mirror cavity, where the mirrors show opposite GDD and simultaneously a mirror reflectivity of 99.2% over 100 nm bandwidth (480 nm - 580 nm).

Visible wavelength astro-comb.

We demonstrate a tunable laser frequency comb operating near 420 nm with mode spacing of 20-50 GHz, usable bandwidth of 15 nm and output power per line of ~20 nW. Using the TRES spectrograph at the Fred Lawrence Whipple Observatory, we characterize this system to an accuracy below 1m/s, suitable for calibrating high-resolution astrophysical spectrographs used, e.g., in exoplanet studies.

In-situ determination of astro-comb calibrator lines to better than 10 cm s(-1).

Improved wavelength calibrators for high-resolution astrophysical spectrographs will be essential for precision radial velocity (RV) detection of Earth-like exoplanets and direct observation of cosmological deceleration. The astro-comb is a combination of an octave-spanning femtosecond laser frequency comb and a Fabry-Pérot cavity used to achieve calibrator line spacings that can be resolved by an astrophysical spectrograph. Systematic spectral shifts associated with the cavity can be 0.1-1 MHz, corresponding to RV errors of 10-100 cm/s, due to the dispersive properties of the cavity mirrors over broad spectral widths. Although these systematic shifts are very stable, their correction is crucial to high accuracy astrophysical spectroscopy. Here, we demonstrate an in-situ technique to determine the systematic shifts of astro-comb lines due to finite Fabry-Pérot cavity dispersion. The technique is practical for implementation at a telescope-based spectrograph to enable wavelength calibration accuracy better than 10 cm/s.

Posture-dependent human 3He lung imaging in an open-access MRI system: initial results.

RATIONALE AND OBJECTIVES: The human lung and its functions are extremely sensitive to orientation and posture, and debate continues as to the role of gravity and the surrounding anatomy in determining lung function and heterogeneity of perfusion and ventilation. However, study of these effects is difficult. The conventional high-field magnets used for most hyperpolarized (3)He magnetic resonance imaging (MRI) of the human lung, and most other common radiologic imaging modalities including positron emission tomography and computed tomography, restrict subjects to lying horizontally, minimizing most gravitational effects. MATERIALS AND METHODS: In this article, we review the motivation for posture-dependent studies of human lung function and present initial imaging results of human lungs in the supine and vertical body orientations using inhaled hyperpolarized (3)He gas and an open-access MRI instrument. The open geometry of this MRI system features a "walk-in" capability that permits subjects to be imaged in vertical and horizontal positions and potentially allows for complete rotation of the orientation of the imaging subject in a two-dimensional plane. RESULTS: Initial results include two-dimensional lung images acquired with approximately 4 x 8 mm in-plane resolution and three-dimensional images with approximately 2-cm slice thickness. CONCLUSIONS: Effects of posture variation are observed, including posture-related effects of the diaphragm and distension of the lungs while vertical.