Unsupervised Segmentation of Knee Bone Marrow Edema-like Lesions Using Conditional Generative Models.

Bone marrow edema-like lesions (BMEL) in the knee have been linked to the symptoms and progression of osteoarthritis (OA), a highly prevalent disease with profound public health implications. Manual and semi-automatic segmentations of BMELs in magnetic resonance images (MRI) have been used to quantify the significance of BMELs. However, their utilization is hampered by the labor-intensive and time-consuming nature of the process as well as by annotator bias, especially since BMELs exhibit various sizes and irregular shapes with diffuse signal that lead to poor intra- and inter-rater reliability. In this study, we propose a novel unsupervised method for fully automated segmentation of BMELs that leverages conditional diffusion models, multiple MRI sequences that have different contrast of BMELs, and anomaly detection that do not rely on costly and error-prone annotations. We also analyze BMEL segmentation annotations from multiple experts, reporting intra-/inter-rater variability and setting better benchmarks for BMEL segmentation performance.

Severe Lacerations in Alpine Ski Racing: A Case Series and Review of the Literature.

STUDY DESIGN: Case series. LEVEL OF EVIDENCE: Level 4C.

Informed Chemical Classification of Organophosphorus Compounds via Unsupervised Machine Learning of X-ray Absorption Spectroscopy and X-ray Emission Spectroscopy.

We analyze an ensemble of organophosphorus compounds to form an unbiased characterization of the information encoded in their X-ray absorption near-edge structure (XANES) and valence-to-core X-ray emission spectra (VtC-XES). Data-driven emergence of chemical classes via unsupervised machine learning, specifically cluster analysis in the Uniform Manifold Approximation and Projection (UMAP) embedding, finds spectral sensitivity to coordination, oxidation, aromaticity, intramolecular hydrogen bonding, and ligand identity. Subsequently, we implement supervised machine learning via Gaussian process classifiers to identify confidence in predictions that match our initial qualitative assessments of clustering. The results further support the benefit of utilizing unsupervised machine learning as a precursor to supervised machine learning, which we term Unsupervised Validation of Classes (UVC), a result that goes beyond the present case of X-ray spectroscopies.

Evaluating diversity in neurosurgery through the use of a multidimensional statistical model: a pilot study.

OBJECTIVE: There is a growing body of evidence demonstrating the benefits of diversity across many domains. However, neurosurgery consistently lags most of medicine in many aspects of diversity. Any inability to make progress in this arena is likely due to the multifactorial and complex nature of the issue, which makes it difficult to meaningfully measure and track diversity within the workforce. The goal of this pilot study was to assess the utilization of a multidimensional statistical model to quantify and assess diversity within neurosurgery. The authors sought to 1) assess the diversity of neurosurgery residents using Simpson's Diversity Index and Sullivan's Composite Diversity Index (CDI) and 2) determine if a medical school's intrinsic academic opportunities and resources, indicated by US News & World Report's (USNWR's) best research medical schools ranking, are related to the number of neurosurgery residents produced per medical school. METHODS: A cross-sectional study of all neurosurgery residents (projected graduation years 2020-2026) and 1st-year medical students (matriculating years 2016-2019) was undertaken. Biographical diversity data (gender and matriculation data) were collected from institutional websites between December 2019 and June 2020. The CDI expresses the diversity of a given population by representing the effective proportion of categories present across all diversity attributes and was calculated for neurosurgery residents and medical students. Statistical results are reported as the median and interquartile range. RESULTS: Neurosurgery residency program CDI (0.21, IQR 0.16-0.25) was significantly less (p < 0.001) than medical school CDI (0.42, 0.37-0.48). There was no significant difference in CDI between top-40 and non-top 40 Doximity ranked research output neurosurgery residency programs (p = 0.35) or between top-40 and non-top 40 USNWR ranked research medical schools (p = 0.11). Over a 7-year period, top-40 ranked research medical schools produced significantly more (p < 0.001) neurosurgery residents (11.9, IQR 7.1-18.9) than the non-top 40 ranked research medical schools (5.6, IQR 2.6-8.5). CONCLUSIONS: The authors demonstrated the feasibility of using a multidimensional statistical model as a measure to understand the complex issues of diversity. Their preliminary data suggested that neurosurgery's challenge in achieving the desired diversity relates to uneven attraction and/or recruitment across an increasingly diverse medical student body. In recent years, neurosurgery has made great progress in the arena of diversity and has shown a strong desire to do more. Utilization of these diversity measures will help the neurosurgery field to monitor progress along this valuable journey.

New Insights into the High-Performance Black Phosphorus Anode for Lithium-Ion Batteries.

Black phosphorus (BP) is a promising anode material in lithium-ion batteries (LIBs) owing to its high electrical conductivity and capacity. However, the huge volume change of BP during cycling induces rapid capacity fading. In addition, the unclear electrochemical mechanism of BP hinders the development of rational designs and preparation of high-performance BP-based anodes. Here, a high-performance nanostructured BP-graphite-carbon nanotubes composite (BP/G/CNTs) synthesized using ball-milling method is reported. The BP/G/CNTs anode delivers a high initial capacity of 1375 mA h g-1 at 0.15 A g-1 and maintains 1031.7 mA h g-1 after 450 cycles. Excellent high-rate performance is demonstrated with a capacity of 508.1 mA h g-1 after 3000 cycles at 2 A g-1 . Moreover, for the first time, direct evidence is provided experimentally to present the electrochemical mechanism of BP anodes with three-step lithiation and delithiation using ex situ X-ray diffraction (XRD), ex situ X-ray absorption spectroscopy (XAS), ex situ X-ray emission spectroscopy, operando XRD, and operando XAS, which reveal the formation of Li3 P7 , LiP, and Li3 P. Furthermore, the study indicates an open-circuit relaxation effect of the electrode with ex situ and operando XAS analyses.

Surface Functionalization of Black Phosphorus with Nitrenes: Identification of P=N Bonds by Using Isotopic Labeling.

Surface functionalization of two-dimensional crystals is a key path to tuning their intrinsic physical and chemical properties. However, synthetic protocols and experimental strategies to directly probe chemical bonding in modified surfaces are scarce. Introduced herein is a mild, surface-specific protocol for the surface functionalization of few-layer black phosphorus nanosheets using a family of photolytically generated nitrenes (RN) from the corresponding azides. By embedding spectroscopic tags in the organic backbone, a multitude of characterization techniques are employed to investigate in detail the chemical structure of the modified nanosheets, including vibrational, X-ray photoelectron, solid state 31 P NMR, and UV-vis spectroscopy. To directly probe the functional groups introduced on the surface, R fragments were selected such that in conjunction with vibrational spectroscopy, 15 N-labeling experiments, and DFT methods, diagnostic P=N vibrational modes indicative of iminophosphorane units on the nanosheet surface could be conclusively identified.

Probing Sulfur Chemical and Electronic Structure with Experimental Observation and Quantitative Theoretical Prediction of Kα and Valence-to-Core Kß X-ray Emission Spectroscopy.

An extensive experimental and theoretical study of the Kα and Kß high-resolution X-ray emission spectroscopy (XES) of sulfur-bearing systems is presented. This study encompasses a wide range of organic and inorganic compounds, including numerous experimental spectra from both prior published work and new measurements. Employing a linear-response time-dependent density functional theory (LR-TDDFT) approach, strong quantitative agreement is found in the calculation of energy shifts of the core-to-core Kα as well as the full range of spectral features in the valence-to-core Kß spectrum. The ability to accurately calculate the sulfur Kα energy shift supports the use of sulfur Kα XES as a bulk-sensitive tool for assessing sulfur speciation. The fine structure of the sulfur Kß spectrum, in conjunction with the theoretical results, is shown to be sensitive to the local electronic structure including effects of symmetry, ligand type and number, and, in the case of organosulfur compounds, to the nature of the bonded organic moiety. This agreement between theory and experiment, augmented by the potential for high-access XES measurements with the latest generation of laboratory-based spectrometers, demonstrates the possibility of broad analytical use of XES for sulfur and nearby third-row elements. The effective solution of the forward problem, i.e., successful prediction of detailed spectra from known molecular structure, also suggests future use of supervised machine learning approaches to experimental inference, as has seen recent interest for interpretation of X-ray absorption near-edge structure (XANES).

Resonant inelastic X-ray scattering using a miniature dispersive Rowland refocusing spectrometer.

X-ray absorption spectroscopy (XAS) beamlines worldwide are steadily increasing their emphasis on full photon-in/photon-out spectroscopies, such as resonant inelastic X-ray scattering (RIXS), resonant X-ray emission spectroscopy (RXES) and high energy resolution fluorescence detection XAS (HERFD-XAS). In such cases, each beamline must match the choice of emission spectrometer to the scientific mission of its users. Previous work has recently reported a miniature tender X-ray spectrometer using a dispersive Rowland refocusing (DRR) geometry that functions with high energy resolution even with a large X-ray spot size on the sample [Holden et al. (2017). Rev. Sci. Instrum. 88, 073904]. This instrument has been used in the laboratory in multiple studies of non-resonant X-ray emission spectroscopy using a conventional X-ray tube, though only for preliminary measurements at a low-intensity microfocus synchrotron beamline. This paper reports an extensive study of the performance of a miniature DRR spectrometer at an unfocused wiggler beamline, where the incident monochromatic flux allows for resonant studies which are impossible in the laboratory. The results support the broader use of the present design and also suggest that the DRR method with an unfocused beam could have important applications for materials with low radiation damage thresholds and that would not survive analysis on focused beamlines.

Acute Nicotine Exposure Alters Ventral Tegmental Area Inhibitory Transmission and Promotes Diazepam Consumption.

Nicotine use increases the risk for subsequent abuse of other addictive drugs, but the biological basis underlying this risk remains largely unknown. Interactions between nicotine and other drugs of abuse may arise from nicotine-induced neural adaptations in the mesolimbic dopamine (DA) system, a common pathway for the reinforcing effects of many addictive substances. Previous work identified nicotine-induced neuroadaptations that alter inhibitory transmission in the ventral tegmental area (VTA). Here, we test whether nicotine-induced dysregulation of GABAergic signaling within the VTA increases the vulnerability for benzodiazepine abuse that has been reported in smokers. We demonstrate in rats that nicotine exposure dysregulates diazepam-induced inhibition of VTA GABA neurons and increases diazepam consumption. In VTA GABA neurons, nicotine impaired KCC2-mediated chloride extrusion, depolarized the GABAA reversal potential, and shifted the pharmacological effect of diazepam on GABA neurons from inhibition toward excitation. In parallel, nicotine-related alterations in GABA signaling observed ex vivo were associated with enhanced diazepam-induced inhibition of lateral VTA DA neurons in vivo Targeting KCC2 with the agonist CLP290 normalized diazepam-induced effects on VTA GABA transmission and reduced diazepam consumption following nicotine administration to the control level. Together, our results provide insights into midbrain circuit alterations resulting from nicotine exposure that contribute to the abuse of other drugs, such as benzodiazepines.

An improved laboratory-based x-ray absorption fine structure and x-ray emission spectrometer for analytical applications in materials chemistry research.

X-ray absorption fine structure (XAFS) and x-ray emission spectroscopy (XES) are advanced x-ray spectroscopies that impact a wide range of disciplines. However, unlike the majority of other spectroscopic methods, XAFS and XES are accompanied by an unusual access model, wherein the dominant use of the technique is for premier research studies at world-class facilities, i.e., synchrotron x-ray light sources. In this paper, we report the design and performance of an improved XAFS and XES spectrometer based on the general conceptual design of Seidler et al. [Rev. Sci. Instrum. 85, 113906 (2014)]. New developments include reduced mechanical degrees of freedom, much-increased flux, and a wider Bragg angle range to enable extended x-ray absorption fine structure (EXAFS) measurement and analysis for the first time with this type of modern laboratory XAFS configuration. This instrument enables a new class of routine applications that are incompatible with the mission and access model of the synchrotron light sources. To illustrate this, we provide numerous examples of x-ray absorption near edge structure (XANES), EXAFS, and XES results for a variety of problems and energy ranges. Highlights include XAFS and XES measurements of battery electrode materials, EXAFS of Ni with full modeling of results to validate monochromator performance, valence-to-core XES for 3d transition metal compounds, and uranium XANES and XES for different oxidation states. Taken en masse, these results further support the growing perspective that modern laboratory-based XAFS and XES have the potential to develop a new branch of analytical chemistry.

Vacuum formed temporary spherically and toroidally bent crystal analyzers for x-ray absorption and x-ray emission spectroscopy.

We demonstrate that vacuum forming of 10-cm diameter silicon wafers of various crystallographic orientations under an x-ray permeable, flexible window can easily generate spherically bent crystal analyzers and toroidally bent crystal analyzers with ∼1-eV energy resolution and a 1-m major radius of curvature. In applications at synchrotron light sources, x-ray free electron lasers, and laboratory spectrometers, these characteristics are generally sufficient for many x-ray absorption fine structure (XAFS), x-ray emission spectroscopy (XES), and resonant inelastic x-ray scattering applications in the chemical sciences. Unlike existing optics manufacturing methods using epoxy or anodic bonding, vacuum forming without adhesive is temporary in the sense that the bent wafer can be removed when vacuum is released and exchanged for a different orientation wafer. Therefore, the combination of an x-ray compatible vacuum-forming chamber, a library of thin wafers, and a small number of forms having different secondary curvatures can give extreme flexibility in spectrometer energy range. As proof of this method, we determine the energy resolution and reflectivity for several such vacuum-formed bent crystal analyzers in laboratory-based XAFS and XES studies using a conventional x-ray tube. For completeness, we also show x-ray images collected on the detector plane to characterize the resulting focal spots and optical aberrations.

A color x-ray camera for 2-6 keV using a mass produced back illuminated complementary metal oxide semiconductor sensor.

There are several reports in the scientific literature of the use of mass-produced charge coupled device or complementary metal oxide semiconductor (CMOS) sensors as x-ray detectors that combine high spatial resolution with significant energy resolution. Exploiting a relatively new especially favorable ambient-temperature back-illuminated CMOS sensor, we report the development of a spectroscopic x-ray camera having particularly impressive performance for 2-6 keV photons. This instrument has several beneficial characteristics for advanced x-ray spectroscopy studies in the laboratory, at synchrotron light sources, at x-ray free electron lasers, or when using pulsed x-ray sources such as for laser plasma physics research. These characteristics include fine position and energy resolution for individual photon events, high saturation rates, frame rates above 100 Hz, easy user maintenance for damaged sensors, and software for real-time processing. We evaluate this camera as an alternative to traditional energy-dispersive solid-state detectors, such as silicon drift detectors, and also illustrate its use in a very high resolution wavelength-dispersive x-ray fluorescence spectrometer (i.e., x-ray emission spectrometer) that has recently been reported elsewhere [W. M. Holden et al., Rev. Sci. Instrum. 88(7), 073904 (2017)].

Programmed environmental illumination during autologous stem cell transplantation hospitalization for the treatment of multiple myeloma reduces severity of depression: A preliminary randomized controlled trial.

BACKGROUND: Over a third of multiple myeloma (MM) patients report clinical levels of depression during autologous stem cell transplant (ASCT) hospitalization. We report preliminary results from a randomized clinical trial investigating the effect of Programmed Environmental Illumination (PEI) of hospital rooms on depression. METHODS: Patients (N = 187) scheduled to receive an ASCT were assessed for eligibility. Those who met study eligibility criteria (n = 44) were randomly assigned to one of two PEI conditions involving delivery of either circadian active bright white light (BWL) or circadian inactive dim white light (DWL) throughout the room from 7 to 10 am daily during hospitalization. Patients completed the Center for Epidemiological Studies Depression Scale (CES-D) prior to hospitalization, at days 2 and 7 post-transplant, and on the third day of engraftment. RESULTS: General linear model analyses revealed no difference between the groups in CES-D total score at baseline (P = 0.7859). A longitudinal linear mixed model analysis revealed a significant interaction between time of assessment and light condition [F(3,107) = 2.90; P = 0.0386; ɳ2  = 0.08)], indicating that PEI prevented the development of depression during hospitalization, with effects reaching significance by the third day of engraftment. At the third day of engraftment, 68.4% of the participants in the DWL comparison condition met the criteria for clinically significant depression compared to 42.1% in the BWL condition. CONCLUSION: These findings demonstrate that PEI using BWL during MM ASCT hospitalization is effective in reducing the development of depression. Future studies should examine the mechanisms whereby PEI improves depression.

Sulfur Speciation in Biochars by Very High Resolution Benchtop Kα X-ray Emission Spectroscopy.

The analytical chemistry of sulfur-containing materials poses substantial technical challenges, especially due to the limitations of 33S NMR and the time-intensive preparations required for wet-chemistry analyses. A number of prior studies have found that synchrotron-based X-ray absorption near edge structure (XANES) measurements can give detailed speciation of sulfur chemistry in such cases. However, due to the obvious access limitations, synchrotron XANES of sulfur cannot be part of routine analytical practice across the chemical sciences community. Here, in a study of the sulfur chemistry in biochars, we compare and contrast the chemical inferences available from synchrotron XANES with that given by benchtop, extremely high resolution wavelength-dispersive X-ray fluorescence (WD-XRF) spectroscopy, also often called X-ray emission spectroscopy (XES). While the XANES spectra have higher total information content, often giving differentiation between different moieties having the same oxidation state, the lower sensitivity of the S Kα XES to coordination and local structure provides pragmatic benefit for the more limited goal of quantifying the S oxidation state distribution. Within that constrained metric, we find good agreement between the two methods. As the sulfur concentrations were as low as 150 ppm, these measurements provide proof-of-principle for characterization of the sulfur chemistry of biochars and potential applications to other areas such as soils, batteries, catalysts, and fossil fuels and their combustion products.

Adolescent Nicotine Exposure Alters GABAA Receptor Signaling in the Ventral Tegmental Area and Increases Adult Ethanol Self-Administration.

Adolescent smoking is associated with pathological drinking later in life, but the biological basis for this vulnerability is unknown. To examine how adolescent nicotine exposure influences subsequent ethanol intake, nicotine was administered during adolescence or adulthood, and responses to alcohol were measured 1 month later. We found that adolescent, but not adult, nicotine exposure altered GABA signaling within the ventral tegmental area (VTA) and led to a long-lasting enhancement of alcohol self-administration. We detected depolarizing shifts in GABAA reversal potentials arising from impaired chloride extrusion in VTA GABA neurons. Alterations in GABA signaling were dependent on glucocorticoid receptor activation and were associated with attenuated dopaminergic neuron responses to alcohol in the lateral VTA. Importantly, enhancing chloride extrusion in adolescent nicotine-treated animals restored VTA GABA signaling and alcohol self-administration to control levels. Taken together, this work suggests that adolescent nicotine exposure increases the risk profile for increased alcohol drinking in adulthood.

A compact dispersive refocusing Rowland circle X-ray emission spectrometer for laboratory, synchrotron, and XFEL applications.

X-ray emission spectroscopy is emerging as an important complement to x-ray absorption fine structure spectroscopy, providing a characterization of the occupied electronic density of states local to the species of interest. Here, we present details of the design and performance of a compact x-ray emission spectrometer that uses a dispersive refocusing Rowland (DRR) circle geometry to achieve excellent performance for the 2-2.5 keV range, i.e., especially for the K-edge emission from sulfur and phosphorous. The DRR approach allows high energy resolution even for unfocused x-ray sources. This property enables high count rates in laboratory studies, approaching those of insertion-device beamlines at third-generation synchrotrons, despite use of only a low-powered, conventional x-ray tube. The spectrometer, whose overall scale is set by use of a 10-cm diameter Rowland circle and a new small-pixel complementary metal-oxide-semiconductor x-ray camera, is easily portable to synchrotron or x-ray free electron laser beamlines. Photometrics from measurements at the Advanced Light Source show excellent overall instrumental efficiency. In addition, the compact size of this instrument lends itself to future multiplexing to gain large factors in net collection efficiency or its implementation in controlled gas gloveboxes either in the lab or in an endstation.

A comparative assessment of major international disasters: the need for exposure assessment, systematic emergency preparedness, and lifetime health care.

BACKGROUND: The disasters at Seveso, Three Mile Island, Bhopal, Chernobyl, the World Trade Center (WTC) and Fukushima had historic health and economic sequelae for large populations of workers, responders and community members. METHODS: Comparative data from these events were collected to derive indications for future preparedness. Information from the primary sources and a literature review addressed: i) exposure assessment; ii) exposed populations; iii) health surveillance; iv) follow-up and research outputs; v) observed physical and mental health effects; vi) treatment and benefits; and vii) outreach activities. RESULTS: Exposure assessment was conducted in Seveso, Chernobyl and Fukushima, although none benefited from a timely or systematic strategy, yielding immediate and sequential measurements after the disaster. Identification of exposed subjects was overall underestimated. Health surveillance, treatment and follow-up research were implemented in Seveso, Chernobyl, Fukushima, and at the WTC, mostly focusing on the workers and responders, and to a lesser extent on residents. Exposure-related physical and mental health consequences were identified, indicating the need for a long-term health care of the affected populations. Fukushima has generated the largest scientific output so far, followed by the WTCHP and Chernobyl. Benefits programs and active outreach figured prominently in only the WTC Health Program. The analysis of these programs yielded the following lessons: 1) Know who was there; 2) Have public health input to the disaster response; 3) Collect health and needs data rapidly; 4) Take care of the affected; 5) Emergency preparedness; 6) Data driven, needs assessment, advocacy. CONCLUSIONS: Given the long-lasting health consequences of natural and man-made disasters, health surveillance and treatment programs are critical for management of health conditions, and emergency preparedness plans are needed to prevent or minimize the impact of future threats.

Cancer in World Trade Center responders: Findings from multiple cohorts and options for future study.

BACKGROUND: Three longitudinal studies of cancer incidence in varied populations of World Trade Center responders have been conducted. METHODS: We compared the design and results of the three studies. RESULTS: Separate analyses of these cohorts revealed excess cancer incidence in responders for all cancers combined and for cancers of the thyroid and prostate. Methodological dissimilarities included recruitment strategies, source of cohort members, demographic characteristics, overlap between cohorts, assessment of WTC and other occupational exposures and confounders, methods and duration of follow-up, approaches for statistical analysis, and latency analyses. CONCLUSIONS: The presence of three cohorts strengthens the effort of identifying and quantifying the cancer risk; the heterogeneity in design might increase sensitivity to the identification of cancers potentially associated with exposure. The presence and magnitude of an increased cancer risk remains to be fully elucidated. Continued long-term follow up with minimal longitudinal dropout is crucial to achieve this goal.