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Objective: To assess the value of material density (MD) images generated from a rapid kilovoltage-switching dual-energy CT (rsDECT) in early detection of peritoneal carcinomatosis (PC). Materials and methods: Thirty patients (60 ± 13 years; 24 women) with PC detected on multiple abdominal DECT scans were included. Four separate DECTs with varying findings of PC from each patient were used for qualitative/quantitative analysis, resulting in a total of 120 DECT scans (n = 30 × 4). Three radiologists independently reviewed DECT images (65 keV alone and 65 keV + MD) for diagnosis of PC (diagnostic confidence, lesion conspicuity, sharpness/delineation and image quality) using a 5-point Likert scale. Quantitative estimation of contrast-to-noise ratio (CNR) was done. Wilcoxon signed-rank test and Odds ratio calculation were used to compare between the two protocols. Inter-observer agreement was evaluated using Kappa coefficient analysis. P values < 0.05 were considered statistically significant. Results: 65 keV + MD images showed a slightly higher sensitivity (89%[95%CI:84,92]) for PC detection compared with 65 keV images alone without statistical significance (84%[95%CI:78,88], p = 0.11) with the experienced reader showing significant improvement (98%[95%CI:93,100] vs. 90%[95%CI:83,94], p = 0.02). On a per-patient basis, use of MD images allowed earlier diagnosis for PC in an additional 13–23% of patients. On sub-group analysis, earlier diagnosis of PC was particularly beneficial in patients with BMI ≤ 29.9 kg/m2. 65 keV + MD images showed higher diagnostic confidence, lesion conspicuity, and lesion sharpness for the experienced reader (p < 0.001). CNR was higher in MD images (1.7 ± 0.5) than 65 keV images (0.1 ± 0.02, p < 0.001). All readers showed moderate interobserver agreement for determining PC by both protocols (κ = 0.58 and κ = 0.47). Conclusion: MD images allow earlier and improved detection of PC with the degree of benefit varying based on reader experience and patient body habitus. [ABSTRACT FROM AUTHOR]

Blood velocities measured by Transcranial Doppler (TCD) are dependent on the angle between the incident ultrasound beam and the direction of blood flow (known as the Doppler angle). However, when TCD examinations are performed without imaging the Doppler angle for each vessel segment is not known. We have measured Doppler angles in the basal cerebral arteries examined with TCD using three-dimensional (3D) vessel models generated from computed tomography angiography (CTA) scans. This approach produces angle statistics that are not accessible during non-imaging TCD studies. We created 3D models of the basal cerebral arteries for 24 vasospasm patients. Standard acoustic windows were mapped to the specific anatomy of each patient. Virtual ultrasound transmit beams were generated that originated from the acoustic window and intersected the centerline of each arterial segment. Doppler angle measurements were calculated and compiled for each vessel segment. Doppler angles were smallest for the middle cerebral artery M1 segment (median 24.6°) and ophthalmic artery (median 25.0°), and largest for the anterior cerebral artery A2 segment (median 76.4°) and posterior cerebral artery P2 segment (median 75.8°). The ophthalmic artery had the highest proportion of Doppler angles that were less than 60° (99%) while the anterior cerebral artery A2 segment had the lowest proportion of Doppler angles that were less than 60° (10%). These angle measurements indicate the expected deviation between measured and true velocities in the cerebral arteries, highlighting specific segments that may be prone to underestimation of velocity. [ABSTRACT FROM AUTHOR]

Here, we introduce the Tabulae Paralytica—a compilation of four atlases of spinal cord injury (SCI) comprising a single-nucleus transcriptome atlas of half a million cells, a multiome atlas pairing transcriptomic and epigenomic measurements within the same nuclei, and two spatial transcriptomic atlases of the injured spinal cord spanning four spatial and temporal dimensions. We integrated these atlases into a common framework to dissect the molecular logic that governs the responses to injury within the spinal cord1. The Tabulae Paralytica uncovered new biological principles that dictate the consequences of SCI, including conserved and divergent neuronal responses to injury; the priming of specific neuronal subpopulations to upregulate circuit-reorganizing programs after injury; an inverse relationship between neuronal stress responses and the activation of circuit reorganization programs; the necessity of re-establishing a tripartite neuroprotective barrier between immune-privileged and extra-neural environments after SCI and a failure to form this barrier in old mice. We leveraged the Tabulae Paralytica to develop a rejuvenative gene therapy that re-established this tripartite barrier, and restored the natural recovery of walking after paralysis in old mice. The Tabulae Paralytica provides a window into the pathobiology of SCI, while establishing a framework for integrating multimodal, genome-scale measurements in four dimensions to study biology and medicine.The Tabulae Paralytica, a compilation of four molecular atlases of spinal cord injury, provides a window into the pathobiology of spinal cord injury, establishing a framework for integrating multimodal, genome-scale measurements in four dimensions to study biology and medicine. [ABSTRACT FROM AUTHOR]

(Soliman, The Accounting Review 83:823–853, 2008) finds that separating return on net operating assets (RNOA) into DuPont components—profit margin and asset turnover—improves prediction of future RNOA. (Dickinson, The Accounting Review 86:1969–1994, 2011) finds that a firm's life-cycle stage explains changes in future RNOA. (Vorst and Yohn, The Accounting Review 93:357–381, 2018) find that life-cycle calibration improves prediction more than industry grouping in prediction models that do not include the DuPont components. We unite and extend the above studies by using data updated since the early 2000s and performing out-of-sample tests. We show that the DuPont components continue to improve prediction of one-year-ahead RNOA. Industry grouping and life-cycle calibration using the components improve prediction further. The improvement by life-cycle calibration is stronger for mature companies, more R&D-intensive companies, less capital-intensive companies, and companies in less concentrated industries. Sell-side equity analysts and investors appear to initially rely more on basic prediction models than the expanded models that include DuPont components, industry grouping, and life-cycle calibration. While there is some evidence of investor surprise associated with the expanded models, hedge portfolios formed based on the expanded model predictions do not produce abnormal returns. [ABSTRACT FROM AUTHOR]

Intellectual property safeguards should be more widely incorporated into the bilateral contracts that underpin the translational R&D process to preserve the public interest, especially where public funds and resources have spearheaded the innovation process. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the recently reported relative diagnostic accuracy of US, CT, MRI, and cholescintigraphy for diagnosing acute cholecystitis. Methods: 2 radiologists independently performed systematic electronic searches for articles published between 2000 and 2021 and applied inclusion/exclusion criteria. 2 different radiologists extracted data from the articles and scored each with a methodological quality tool. Pooled estimates of sensitivity and specificity were calculated with a bivariate linear mixed model. A second analysis made head-to-head comparisons (US vs. CT, US vs. cholescintigraphy). Factors were also analyzed for potential confounding effects on diagnostic accuracy. Results: Of 6121 initial titles, 22 were included. The prevalence of cholecystitis varied widely across studies (9.4–98%). Pooled sensitivity and specificity estimates were 69% (confidence limit [CL] 62–76%) and 79% (CL 71–86%) for US, 91% (CL 86–94%) and 63% (CL 51–74%) for cholescintigraphy, 78% (CL 69–84%) and 81% (CL 71–88%) for CT, and 91% (CL 78–97%) and 93% (CL 70–99%) for MRI. Regarding head-to-head comparisons, the sensitivity of CT (87.6%, CL 70–96%) was significantly higher than US (66.8%, CL 43–84%), while specificities (81.7% with CL 54–95% for US, 91.9% with CL 67–99% for CT) were similar. The sensitivity of cholescintigraphy (87.4%, CL 76–94%) was significantly greater than US (61.6%, CL 44–77%), while the specificity of US (82%, CL 65–92%) was significantly higher than cholescintigraphy (68%, CL 47–84%). Conclusion: Recent data suggests that CT may have a higher sensitivity than US for diagnosing acute cholecystitis, with similar specificity. Cholescintigraphy remains a highly sensitive modality with lower specificity than previously reported. MRI remains under studied, but with promising results. [ABSTRACT FROM AUTHOR]

Purpose: To compare outcomes of robotic and open repair for uncomplicated, moderate-sized, midline ventral hernias. Methods: From 2017 to 2021, patient characteristics and 30 day outcomes for all ventral hernias at our center were prospectively collected. We studied hernias potentially suitable for robotic repair: elective, midline, 3–10 cm rectus separation, no prior mesh, and no need for concomitant procedure. Robotic or open repair was performed by surgeon or patient preference. The primary outcome was any complication using Clavien–Dindo scoring. Secondary outcomes were operative time, length-of-stay, and readmissions. Regression identified predictors of complications. Results: Of 648 hernias repaired, 70 robotic and 52 open repairs met inclusion criteria. The groups had similar patient demographics, co-morbidities, and hernia size, except that there were more immunosuppressed patients in the open group (11 versus 5 patients, p = 0.031). Complications occurred after 7 (13%) open repairs versus 2 (3%) robotic repairs, p = 0.036. Surgical site infection occurred after four open repairs but no robotic repair, p = 0.004. Length-of-stay averaged almost 3 days longer after open repair (4.3 ± 2.7 days versus 1.5 ± 1.4 days, p = 0.031). Readmission occurred after 6 (12%) oppen repairs but only 1 (1%) robotic repair. A long-term survey (61% response rate after mean follow-up of 2.8 years) showed that the HerQLes QOL score was better after robotic repair (46 ± 15 versus 40 ± 17, = 0.049). In regression models, only open technique predicted complications. Conclusions: Robotic techniques were associated with fewer complications, shorter hospitalization, fewer infections, and fewer readmissions compared to open techniques. Open surgical technique was the only predictor of complications. [ABSTRACT FROM AUTHOR]

Research that relates corporate social responsibility (CSR) to earnings management (EM) interprets directional relations between CSR and EM as indicators of opportunistic or ethical behavior by managers. On the one hand, EM leads to higher levels of CSR by opportunistic managers seeking reputational benefits from CSR. On the other hand, CSR leads to lower levels of EM by managers whose engagement in CSR reflects their ethical values. The attribution of opportunistic and ethical behaviors to managers in a firm setting is incomplete without also considering how EM and CSR relate to what firms strive to do as economic entities – create value. Therefore, we introduce financial performance (represented by Tobin's Q) as an endogenous variable that influences managers' engagement in CSR and EM. We estimate a panel vector auto-regression (PVAR) model to evaluate the complex directional relations between CSR, EM and Q. We find that EM positively affects CSR, consistent with reputation-building, but we find no directional relation from CSR to EM. We find that firm performance (Q) positively affects EM, suggesting that EM may be economically motivated, and that CSR positively affects Q, consistent with economic motives driving engagement in CSR. Our analysis addresses endogeneity concerns and provides a more complete basis for ascribing managers' decisions about CSR and EM to economic and behavioral motives. [ABSTRACT FROM AUTHOR]

Memory is fleeting. To avoid information loss, humans need to recode verbal stimuli into chunks of limited duration, each containing multiple words. Chunk duration may also be limited neurally by the wavelength of periodic brain activity, so-called neural oscillations. While both cognitive and neural constraints predict some degree of behavioral regularity in processing, this remains to be shown. Our analysis of self-paced reading data from 181 participants reveals periodic patterns at a frequency of ∼ 2 Hz. We defined multi-word chunks by using a computational formalization based on dependency annotations and part-of-speech tags. Potential chunk outputs were first generated from the computational formalization and the final chunk outputs were selected based on normalized pointwise mutual information. We show that behavioral periodicity is time-aligned to multi-word chunks, suggesting that the multi-word chunks generated from local dependency clusters may minimize memory demands. This is the first evidence that sentence processing behavior is periodic, consistent with a role of both memory constraints and endogenous electrophysiological rhythms in the formation of chunks during language comprehension. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic, systemic inflammatory condition primarily affecting skin. While the role of the immune compartment (e.g., T cells) is well established, the changes in the skin compartment are more poorly understood. Using longitudinal skin biopsies (n = 375) from the "Psoriasis Treatment with Abatacept and Ustekinumab: A Study of Efficacy"(PAUSE) clinical trial (n = 101), we report 953 expression quantitative trait loci (eQTLs). Of those, 116 eQTLs have effect sizes that were modulated by local skin inflammation (eQTL interactions). By examining these eQTL genes (eGenes), we find that most are expressed in the skin tissue compartment, and a subset overlap with the NRF2 pathway. Indeed, the strongest eQTL interaction signal – rs1491377616-LCE3C – links a psoriasis risk locus with a gene specifically expressed in the epidermis. This eQTL study highlights the potential to use biospecimens from clinical trials to discover in vivo eQTL interactions with therapeutically relevant environmental variables. Psoriasis is a chronic, systemic inflammatory condition primarily affecting skin. Here, the authors investigate the genetic basis of gene expression in skin biopsies from psoriasis patients and interactions with inflammation to better understand mechanisms of the disease. [ABSTRACT FROM AUTHOR]

Purpose: To externally validate an algorithm for non-invasive differentiation of hepatic mucinous cystic neoplasms (MCN) from benign hepatic cysts (BHC), which differ in management. Methods: Patients with cystic liver lesions pathologically confirmed as MCN or BHC between January 2005 and March 2022 from multiple institutions were retrospectively included. Five readers (2 radiologists, 3 non-radiologist physicians) independently reviewed contrast-enhanced CT or MRI examinations before tissue sampling and applied the 3-feature classification algorithm described by Hardie et al. to differentiate between MCN and BHC, which had a reported accuracy of 93.5%. The classification was then compared to the pathology results. Interreader agreement between readers across different levels of experience was evaluated with Fleiss' Kappa. Results: The final cohort included 159 patients, median age of 62 years (IQR [52.0, 70.0]), 66.7% female (106). Of all patients, 89.3% (142) had BHC, and the remaining 10.7% (17) had MCN on pathology. Agreement for class designation between the radiologists was almost perfect (Fleiss' Kappa 0.840, p < 0.001). The algorithm had an accuracy of 98.1% (95% CI [94.6%, 99.6%]), a positive predictive value of 100.0% (95% CI [76.8%, 100.0%]), a negative predictive value of 97.9% (95% CI [94.1%, 99.6%]), and an area under the receiver operator characteristic curve (AUC) of 0.911 (95% CI [0.818, 1.000]). Conclusion: The evaluated algorithm showed similarly high diagnostic accuracy in our external, multi-institutional validation cohort. This 3-feature algorithm is easily and rapidly applied and its features are reproducible among radiologists, showing promise as a clinical decision support tool. [ABSTRACT FROM AUTHOR]

Sclerosing cholangitis is a chronic cholestatic disease characterized by stricturing, beading, and obliterative fibrosis of the bile ducts. Sclerosing cholangitis is considered primary (PSC) if no underlying etiology is identified or secondary (SSC) if related to another identifiable cause. In this article, we will review the clinical features, pathogenesis, diagnosis, and imaging findings of PSC and SSC, with an emphasis on features that may aid in the distinction of these entities. We will also discuss various etiologies of SSC including recurrent pyogenic cholangitis, other infectious etiologies, ischemic damage, toxic insults, and immunologic, congenital, and miscellaneous causes, highlighting the unique imaging findings and clinical context of each diagnosis. [ABSTRACT FROM AUTHOR]

This review will provide an overview of hepatobiliary mucinous cystic neoplasms and their mimics such as complex appearing benign cysts, intraductal papillary neoplasm of bile ducts, choledochal cysts, infectious cysts, and other cystic neoplasms. Preoperative imaging, particularly abdominal MRI with MRCP, plays a key role in differentiating these entities which differ widely in management. Familiarity with the differentiating imaging features of mucinous cystic neoplasms and their mimics allows radiologists to provide management-guiding reports. [ABSTRACT FROM AUTHOR]

Magnetic resonance cholangiopancreatography (MRCP) has become a widely accepted noninvasive diagnostic tool in the assessment of pancreatic and biliary disease. MRCP essentially exploits extended T2 relaxation times of slow-moving fluid and delineates the outline of biliary and pancreatic ducts on T2-weighted images. In order to maximize the clinical implication of MRCP, it is of utmost importance for radiologists to optimize the acquisition technique, be aware of patient-related factors and physiologic changes than can affect its performance and interpretation. It is critical to understand the most common artifacts and pitfalls encountered during acquisition and interpretation of MRCP. We provide a general overview of the different pitfalls encountered in MRCP and pearls on how to manage them in real-world practice. [ABSTRACT FROM AUTHOR]

We present a convolutional autoencoder to denoise pulses from a p-type point contact high-purity germanium detector similar to those used in several rare event searches. While we focus on training procedures that rely on detailed detector physics simulations, we also present implementations requiring only noisy detector pulses to train the model. We validate our autoencoder on both simulated data and calibration data from an 241 Am source, the latter of which is used to show that the denoised pulses are statistically compatible with data pulses. We demonstrate that our denoising method is able to preserve the underlying shapes of the pulses well, offering improvement over traditional denoising methods. We also show that the shaping time used to calculate energy with a trapezoidal filter can be significantly reduced while maintaining a comparable energy resolution. Under certain circumstances, our denoising method can improve the overall energy resolution. The methods we developed to remove electronic noise are straightforward to extend to other detector technologies. Furthermore, the latent representation from the encoder is also of use in quantifying shape-based characteristics of the signals. Our work has great potential to be used in particle physics experiments and beyond. [ABSTRACT FROM AUTHOR]

The mutualistic relationship of gut-resident microbiota and the host immune system promotes homeostasis that ensures maintenance of the microbial community and of a largely non-aggressive immune cell compartment1,2. The consequences of disturbing this balance include proximal inflammatory conditions, such as Crohn’s disease, and systemic illnesses. This equilibrium is achieved in part through the induction of both effector and suppressor arms of the adaptive immune system. Helicobacter species induce T regulatory (Treg) and T follicular helper (TFH) cells under homeostatic conditions, but induce inflammatory T helper 17 (TH17) cells when induced Treg (iTreg) cells are compromised3,4. How Helicobacter and other gut bacteria direct T cells to adopt distinct functions remains poorly understood. Here we investigated the cells and molecular components required for iTreg cell differentiation. We found that antigen presentation by cells expressing RORγt, rather than by classical dendritic cells, was required and sufficient for induction of Treg cells. These RORγt+ cells—probably type 3 innate lymphoid cells and/or Janus cells5—require the antigen-presentation machinery, the chemokine receptor CCR7 and the TGFβ activator αv integrin. In the absence of any of these factors, there was expansion of pathogenic TH17 cells instead of iTreg cells, induced by CCR7-independent antigen-presenting cells. Thus, intestinal commensal microbes and their products target multiple antigen-presenting cells with pre-determined features suited to directing appropriate T cell differentiation programmes, rather than a common antigen-presenting cell that they endow with appropriate functions.Induction of T regulatory cells by gut microbes is mediated by antigen-presenting RORγt+ cells, unlike that of T follicular helper and T helper 17 cells, which requires different cell types. [ABSTRACT FROM AUTHOR]

Purpose: Prior case reports have noted an increase in renal size and perinephric stranding accompanying immunotherapy-related renal toxicity due to checkpoint-inhibitor therapy. The purpose of this investigation was to systematically evaluate if immunotherapy-related renal toxicity affects renal size and possible associated imaging findings. Methods: This retrospective multi-hospital study included 25 patients (13 men), mean age 67 years (range 46–83) who received immune-checkpoint inhibitors for cancer treatment, developed biopsy-proven immunotherapy-related nephritis, and who also had abdominal imaging before, during, and after nephritis was diagnosed. Long axis renal diameter, renal corticomedullary differentiation/enhancement and perinephric stranding were evaluated by two readers at three timepoints: (1) prior to checkpoint inhibitor therapy (baseline), (2) after biopsy-proven immunotherapy-related nephritis (post-treatment), and (3) following renal function recovery (follow-up). Intraclass correlation coefficient and Cohen's Kappa were calculated to quantify agreement. Logistic regression analysis was implemented to measure the association between each timepoint and imaging features. Results: Reader agreement on kidney measurements was excellent (ICC = 0.87). There was an increase in renal size between baseline and post-treatment (p = 0.001), followed by a decrease between post-treatment to follow-up (p < 0.001). Agreement was perfect for abnormal renal corticomedullary differentiation/enhancement (Kappa = 1, p < 0.001) and almost perfect for perinephric stranding (Kappa = 0.97, p < 0.001). Neither post-treatment nor follow-up imaging findings were significantly associated with these findings compared to the baseline (p = 0.2–0.6). Conclusion: Immunotherapy-related renal toxicity was associated with an increase in renal size coincident with acute renal dysfunction. [ABSTRACT FROM AUTHOR]

Peripheral ossifying fibromas (POFs) and peripheral odontogenic fibromas (POdFs) appear clinically similar but of different histogenesis. The novel marker SATB2 is involved in regulation of osteoblastic differentiation and phenotype. However, SATB2 expression has not been previously explored in POFs and POdFs. Given the potential for mineralized tissue formation in POFs and POdFs, and to more clarify the phenotype of the lesional cells, this study was aimed to immunohistochemically investigate SATB2 expression in POFs and POdFs. Fourteen cases of POF and POdF (7 cases each) were selected, stained for SATB2 immunohistochemically, and scored according to the percentage of positive lesional cells (0, no staining; 1 +, < 5%; 2 +, 5–25%; 3 +, 26–50%; 4 +, 51–75%; and 5 +, 76–100%), and the intensity of staining was graded as weak, moderate, or strong. The control group included the inflammatory fibrous hyperplasia-like area present in two cases, 1 case fibroma, and 1 case giant cell fibroma. Moderate to strong, and diffuse SATB2 nuclear immunoreactivity was detected in the lesional cells of all cases of POFs and POdFs with variable scores; 3–5 + for the POFs and 3–4 + for the POdFs (P = 0.101). The distribution of staining was more prominent in those lesional cells associated with the osteoid/calcification in the cases of POFs. No staining was noted in the control group. The lesional cells in both POFs and POdFs express SATB2 and may exhibit the osteoblastic-like phenotype. SATB2 staining may be useful for diagnosis of subsets of POFs with minimal or absent calcification and some POdFs with unidentifiable odontogenic epithelium. [ABSTRACT FROM AUTHOR]

Despite guidelines developed to standardize the diagnosis and management of gastrointestinal (GI) bleeding, significant variability remains in recommendations and practice. The purpose of this survey was to obtain information on practice patterns for the evaluation of overt lower GI bleeding (LGIB) and suspected small bowel bleeding. A 34-question electronic survey was sent to all Society of Abdominal Radiology (SAR) members. Responses were received from 52 unique institutions (40 from the United States). Only 26 (50%) utilize LGIB management guidelines. 32 (62%) use CT angiography (CTA) for initial evaluation in unstable patients. In stable patients with suspected LGIB, CTA is the preferred initial exam at 21 (40%) versus colonoscopy at 24 (46%) institutions. CTA use increases after hours for both unstable (n = 32 vs. 35, 62% vs. 67%) and stable patients (n = 21 vs. 27, 40% vs 52%). CTA is required before conventional angiography for stable (n = 36, 69%) and unstable (n = 15, 29%) patients. 38 (73%) institutions obtain two post-contrast phases for CTA. 49 (94%) institutions perform CT enterography (CTE) for occult small bowel bleeding with capsule endoscopy (n = 26, 50%) and CTE (n = 21, 40%) being the initial test performed. 35 (67%) institutions perform multiphase CTE for occult small bowel bleeding. In summary, stable and unstable patients with overt lower GI are frequently imaged with CTA, while CTE is frequently performed for suspected occult small bowel bleeding. [ABSTRACT FROM AUTHOR]

This paper demonstrates how an analytical and experimental method can be used to rapidly define the additive manufacturing settings for a new alloy where the process parameters were previously unknown. A nickel-based superalloy, Haynes 282, was chosen for the analysis. An experimental matrix of focused processing parameters was predicted with a dimensionless number and 100 samples were printed using the Laser Powder Bed Fusion technique. High-throughput measurements validated the predicted process conditions needed to achieve desired density and hardness. The whole process was completed in 16 hours. The new technique was confirmed with analytical processing maps adopted by the metal additive manufacturing community. With the predicted set of process parameters, a low-throughput analyses of conventional microstructural characterizations and tensile testing were used to test the predictions. The resultant as-fabricated microstructures have refined length scales of both microsegregation and secondary phase distributions. The mechanical properties were comparable within the predicted processing window and exhibited high strength and high ductility. [ABSTRACT FROM AUTHOR]

Background: Per oral endoscopic myotomy (POEM) is used to treat a variety of esophageal motility disorders and is associated with relatively few complications. However, complications in patients on antithrombotic therapy (AT) is not well-studied. We hypothesize AT patients have a higher risk of post-operative bleeding and 30-day complication rate compared to all other patients, even when these medications are held peri-operatively. Methods: A single-institution retrospective review of a prospectively collected database of patients who underwent POEM procedures January 2011–July 2019 was performed. All 30-day complications were recorded, as well as management of AT medications peri-operatively. Demographic and clinical characteristics were compared using t test, Chi-Square, and Fisher's exact test as appropriate. Multivariate logistic regression was performed to examine factors associated with post-operative complications. Results: A total of 219 POEM procedures were performed. 50.2% of patients were male, and AT patients tended to be older (66.9 vs. 55.4, p = 0.01). The major complication rate was higher among AT patients (36.8% vs. 9.0%, p = 0.01), as was the rate of post-operative bleeding (10.5% vs. 1.0%, p = 0.04). After adjusting for gender and age, the use of antithrombotic therapy was significantly associated with 30-day complications (OR 6.03, p = 0.001). Conclusions: Patients on AT who undergo POEM are significantly more likely to experience complications, including bleeding, within 30 days of surgery. Safe timing of post-operative resumption of antithrombotic medications remains a difficult decision that must be carefully considered by the endoscopist. [ABSTRACT FROM AUTHOR]

Differential expression analysis in single-cell transcriptomics enables the dissection of cell-type-specific responses to perturbations such as disease, trauma, or experimental manipulations. While many statistical methods are available to identify differentially expressed genes, the principles that distinguish these methods and their performance remain unclear. Here, we show that the relative performance of these methods is contingent on their ability to account for variation between biological replicates. Methods that ignore this inevitable variation are biased and prone to false discoveries. Indeed, the most widely used methods can discover hundreds of differentially expressed genes in the absence of biological differences. To exemplify these principles, we exposed true and false discoveries of differentially expressed genes in the injured mouse spinal cord. Differential expression analysis of single-cell transcriptomics allows scientists to dissect cell-type-specific responses to biological perturbations. Here, the authors show that many commonly used methods are biased and can produce false discoveries. [ABSTRACT FROM AUTHOR]

Background: Oligometastatic colorectal cancer (CRC) is potentially curable and demands individualised strategies. Methods: This single-centre retrospective study investigated if positron emission tomography (PET)/magnetic resonance imaging (MR) had a clinical impact on oligometastatic CRC relative to the standard of care imaging (SCI). Adult patients with oligometastatic CRC on SCI who also underwent PET/MR between 3/2016 and 3/2019 were included. The exclusion criterion was lack of confirmatory standard of reference, either surgical pathology, intraoperative gross confirmation or imaging follow-up. SCI consisted of contrast-enhanced (CE) computed tomography (CT) of the chest/abdomen/pelvis, abdominal/pelvic CE-MR, and/or CE whole-body PET/CT with diagnostic quality (i.e. standard radiation dose) CT. Follow-up was evaluated until 3/2020. Results: Thirty-one patients constituted the cohort, 16 (52%) male, median patient age was 53 years (interquartile range: 49–65 years). PET/MR and SCI results were divergent in 19% (95% CI 9–37%) of the cases, with PET/MR leading to management changes in all of them. The diagnostic accuracy of PET/MR was 90 ± 5%, versus 71 ± 8% for SCI. In a pairwise analysis, PET/MR outperformed SCI when compared to the reference standard (p = 0.0412). Conclusions: These findings suggest the potential usefulness of PET/MR in the management of oligometastatic CRC. [ABSTRACT FROM AUTHOR]

The Scanning Habitable Environments with Raman and Luminescence for Organics and Chemicals (SHERLOC) is a robotic arm-mounted instrument on NASA's Perseverance rover. SHERLOC has two primary boresights. The Spectroscopy boresight generates spatially resolved chemical maps using fluorescence and Raman spectroscopy coupled to microscopic images (10.1 μm/pixel). The second boresight is a Wide Angle Topographic Sensor for Operations and eNgineering (WATSON); a copy of the Mars Science Laboratory (MSL) Mars Hand Lens Imager (MAHLI) that obtains color images from microscopic scales (∼13 μm/pixel) to infinity. SHERLOC Spectroscopy focuses a 40 μs pulsed deep UV neon-copper laser (248.6 nm), to a ∼100 μm spot on a target at a working distance of ∼48 mm. Fluorescence emissions from organics, and Raman scattered photons from organics and minerals, are spectrally resolved with a single diffractive grating spectrograph with a spectral range of 250 to ∼370 nm. Because the fluorescence and Raman regions are naturally separated with deep UV excitation (<250 nm), the Raman region ∼ 800 – 4000 cm−1 (250 to 273 nm) and the fluorescence region (274 to ∼370 nm) are acquired simultaneously without time gating or additional mechanisms. SHERLOC science begins by using an Autofocus Context Imager (ACI) to obtain target focus and acquire 10.1 μm/pixel greyscale images. Chemical maps of organic and mineral signatures are acquired by the orchestration of an internal scanning mirror that moves the focused laser spot across discrete points on the target surface where spectra are captured on the spectrometer detector. ACI images and chemical maps (< 100 μm/mapping pixel) will enable the first Mars in situ view of the spatial distribution and interaction between organics, minerals, and chemicals important to the assessment of potential biogenicity (containing CHNOPS). Single robotic arm placement chemical maps can cover areas up to 7x7 mm in area and, with the < 10 min acquisition time per map, larger mosaics are possible with arm movements. This microscopic view of the organic geochemistry of a target at the Perseverance field site, when combined with the other instruments, such as Mastcam-Z, PIXL, and SuperCam, will enable unprecedented analysis of geological materials for both scientific research and determination of which samples to collect and cache for Mars sample return. [ABSTRACT FROM AUTHOR]

The supercritical carbon dioxide (s-CO2) Brayton cycle is currently being explored as a replacement for the steam Rankine cycle due to its potential for higher efficiency and lower cycle cost. 316 stainless steel is a candidate alloy for use in s-CO2 up to roughly 600 °C, but the mechanical effects of prolonged exposure of base and welded material in s-CO2 have not been analyzed. The potential for carburization makes this an important concern for the implementation of 316 and similar austenitic stainless steels in the s-CO2 environment. In this study, welded and base material of two types of 316–316L and 316H–were exposed in either s-CO2 or argon at 550 °C or 750 °C for 1000 h. 550 °C s-CO2 exposure yielded a thin (< 1 µm) Cr oxide with occasional nodules of duplex Fe oxide and Fe–Cr spinel that were up to 5 microns thick. However, tensile results from s-CO−2 exposure matched those of 550 °C thermal aging in Ar, indicating that no mechanically detrimental carburization occurred in either 316 variant after 1000 h exposure. Conversely, 750 °C s-CO2 exposure produced roughly 10 × the oxide thickness, with a more substantial Fe oxide (3–5 µm) on the majority of the surface and nodules of up to 40 µm thick. In comparison to aged samples, tensile testing of 750 °C CO2-exposed samples revealed ductility loss attributed to carburization. Projections of 316L performance in s-CO2 indicate that mechanically detrimental carburization—equal to that shown here for 750 °C, 1000 h—will likely be present after 7–14 years of service at 550 °C. [ABSTRACT FROM AUTHOR]

Purpose: Depatux-m is an antibody drug conjugate (ADC) that targets and inhibits growth of cancer cells overexpressing the epidermal growth factor receptor (EGFR) or the 2–7 deletion mutant (EGFRvIII) in tumor models in vitro and in vivo. Treatment of patients suffering from relapsed/refractory glioblastoma (GBM) with a combination of depatux-m and temozolomide (TMZ) tended to increase overall survival. As a first step to understand the nature of the interaction between the two drugs, we investigated whether the interaction was synergistic, additive or antagonistic. Methods: The efficacy of ADCs, antibodies, TMZ and radiation was tested in xenograft models of GBM, U-87MG and U-87MG EGFRvIII. Both models express EGFR. U-87MG EGFRvIII was transduced to express EGFRvIII. Changes in tumor volume, biomarkers of cell death and apoptosis after treatment were used to measure efficacy of the various treatments. Synergism of depatux-m and TMZ was verified in three-dimensional cultures of U-87MG and U-87MG EGFRvIII by the method of Chou and Talalay. Results: Combined with TMZ and radiotherapy (RT), depatux-m inhibited xenograft growth of U-87MG and U-87MG EGFRvIII more than either treatment with depatux-m or TMZ + RT. Durability of the response to depatux-m + TMZ + RT or depatux-m + TMZ was more pronounced in U-87MG EGFRvIII than in U-87MG. Efficacy of depatux-m + TMZ was synergistic in U-87MG EGFRvIII and additive in U-87MG. Conclusion: Adding depatux-m enhances the efficacy of standard of care therapy in preclinical models of GBM. Durability of response to depatux-m + TMZ in vivo and synergy of the drug-drug interaction correlates with the amount of antigen expressed by the tumor cells. [ABSTRACT FROM AUTHOR]

The thymus' key function in the immune system is to provide the necessary environment for the development of diverse and self-tolerant T lymphocytes. While recent evidence suggests that the thymic stroma is comprised of more functionally distinct subpopulations than previously appreciated, the extent of this cellular heterogeneity in the human thymus is not well understood. Here we use single-cell RNA sequencing to comprehensively profile the human thymic stroma across multiple stages of life. Mesenchyme, pericytes and endothelial cells are identified as potential key regulators of thymic epithelial cell differentiation and thymocyte migration. In-depth analyses of epithelial cells reveal the presence of ionocytes as a medullary population, while the expression of tissue-specific antigens is mapped to different subsets of epithelial cells. This work thus provides important insight on how the diversity of thymic cells is established, and how this heterogeneity contributes to the induction of immune tolerance in humans. The thymus supports T cell immunity by providing the environment for thymocyte differentiation. Here the authors profile human thymic stroma at the single cell level, identifying ionocytes as a new medullary population and defining tissue specific antigen expression in multiple stromal cell types. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) induces haemodynamic instability that threatens survival1–3, impairs neurological recovery4,5, increases the risk of cardiovascular disease6,7, and reduces quality of life8,9. Haemodynamic instability in this context is due to the interruption of supraspinal efferent commands to sympathetic circuits located in the spinal cord10, which prevents the natural baroreflex from controlling these circuits to adjust peripheral vascular resistance. Epidural electrical stimulation (EES) of the spinal cord has been shown to compensate for interrupted supraspinal commands to motor circuits below the injury11, and restored walking after paralysis12. Here, we leveraged these concepts to develop EES protocols that restored haemodynamic stability after SCI. We established a preclinical model that enabled us to dissect the topology and dynamics of the sympathetic circuits, and to understand how EES can engage these circuits. We incorporated these spatial and temporal features into stimulation protocols to conceive a clinical-grade biomimetic haemodynamic regulator that operates in a closed loop. This ‘neuroprosthetic baroreflex’ controlled haemodynamics for extended periods of time in rodents, non-human primates and humans, after both acute and chronic SCI. We will now conduct clinical trials to turn the neuroprosthetic baroreflex into a commonly available therapy for people with SCI.An epidural spinal cord stimulation system regulates blood pressure in the acute and chronic phases of spinal cord injury. [ABSTRACT FROM AUTHOR]

Purpose: Limited data are available on venovenous extracorporeal membrane oxygenation (ECMO) in patients with severe hypoxemic respiratory failure from coronavirus disease 2019 (COVID-19). Methods: We examined the clinical features and outcomes of 190 patients treated with ECMO within 14 days of ICU admission, using data from a multicenter cohort study of 5122 critically ill adults with COVID-19 admitted to 68 hospitals across the United States. To estimate the effect of ECMO on mortality, we emulated a target trial of ECMO receipt versus no ECMO receipt within 7 days of ICU admission among mechanically ventilated patients with severe hypoxemia (PaO2/FiO2 < 100). Patients were followed until hospital discharge, death, or a minimum of 60 days. We adjusted for confounding using a multivariable Cox model. Results: Among the 190 patients treated with ECMO, the median age was 49 years (IQR 41–58), 137 (72.1%) were men, and the median PaO2/FiO2 prior to ECMO initiation was 72 (IQR 61–90). At 60 days, 63 patients (33.2%) had died, 94 (49.5%) were discharged, and 33 (17.4%) remained hospitalized. Among the 1297 patients eligible for the target trial emulation, 45 of the 130 (34.6%) who received ECMO died, and 553 of the 1167 (47.4%) who did not receive ECMO died. In the primary analysis, patients who received ECMO had lower mortality than those who did not (HR 0.55; 95% CI 0.41–0.74). Results were similar in a secondary analysis limited to patients with PaO2/FiO2 < 80 (HR 0.55; 95% CI 0.40–0.77). Conclusion: In select patients with severe respiratory failure from COVID-19, ECMO may reduce mortality. [ABSTRACT FROM AUTHOR]

We present Augur, a method to prioritize the cell types most responsive to biological perturbations in single-cell data. Augur employs a machine-learning framework to quantify the separability of perturbed and unperturbed cells within a high-dimensional space. We validate our method on single-cell RNA sequencing, chromatin accessibility and imaging transcriptomics datasets, and show that Augur outperforms existing methods based on differential gene expression. Augur identified the neural circuits restoring locomotion in mice following spinal cord neurostimulation. The cell types affected by biological perturbations in complex tissues are uncovered by single-cell analysis. [ABSTRACT FROM AUTHOR]

Grade 92 ferritic-martensitic steel is a candidate alloy for medium temperature (< 550 °C) components for the supercritical carbon dioxide (s-CO2) Brayton cycle. 1000 hours exposures were performed on base and welded material in s-CO2 at temperatures of 450 °C or 550 °C and compared to samples aged in Ar at 550 °C. Both s-CO2 exposures resulted in a duplex oxide growth and carburization, with 450 °C exhibiting carburization in a power law diffusion profile up to a depth of 200-250 µm, while 550 °C showed a linear profile up to a depth of 100 µm. The different profiles indicate much slower precipitation and coarsening of carbides at the lower temperature, allowing carbon to diffuse deeper into the material. However, 450 °C produced improved mechanical properties while 550 °C produced deteriorated properties. This was due to the higher density of carbon near the metal–oxide interface which leads to significant carbide coarsening and, subsequently, crack initiation and early failure. Additional exposure at 450 °C is predicted to increase deposited carbon, but further study would be needed to understand if and when carburization will produce a negative mechanical effect. [ABSTRACT FROM AUTHOR]

A TiNxOy (TiNO) material system has been synthesized in thin film form for the first time using a pulsed laser deposition process. X-ray diffraction and X-ray photoelectron spectroscopy measurements have been carried out to show partial oxidation of TiN to TiNO. The current (I)-voltage (V) characteristics recorded from TiNO films sandwiched between indium tin oxide (ITO) and gold (Au) layers and/or copper (Cu) electrodes have shown that the I–V curves lie in the first and third quadrants (i.e., both I and V are either positive or negative) in the dark conditions, while the I–V curves lie in the second and fourth quadrants (i.e., I and V with opposite sign) in the illuminated conditions. The positive sign of power (I × V = Positive) under dark conditions indicates dissipation of power in the TiNO system, while the negative sign of the power (I × V = Negative) under optical illumination indicates the power generation capability of TiNO system. The bandgap of the TiNO thin film samples, measured using ultra violet (UV)–visible (400–800 nm) spectroscopy, was found to be ~ 1.6 eV. As the number of photocatalysts/semiconductors that are active under the visible light irradiation is very limited, our approach to develop a unique visible-light-driven TiNO photoactive material system can open a new avenue for the realization of novel optical devices. [ABSTRACT FROM AUTHOR]

We selected 116 convalescent plasma samples from unique donors who had previously been hospitalized for COVID-19, and found that 4/116 (3%) plasma samples were positive for anti-IFN- 2 autoantibodies (Fig. While we previously found non-hospitalized donors to be anti-IFN- 2 negative [[4]], the data presented here suggest that COVID-19 convalescent plasma from previously hospitalized patients may require screening for type I interferon autoantibodies. [Extracted from the article]

Objective: To correlate MRI findings of patients with posterior cruciate ligament (PCL) injury and surgical management.Materials and methods: A retrospective search yielded 79 acute PCL injuries (36 ± 16 years old, 21 F, 58 M). Two independent readers graded PCL tear location (proximal, middle, or distal third) and severity (low-grade or high-grade partial/complete) and evaluated injury of other knee structures. When available, operative reports were examined and the performed surgical procedure was compared with injury grade, location, and presence of associated injuries.Results: The most commonly injured knee structures in acute PCL tears were posterolateral corner (58/79, 73%) and anterior cruciate ligament (ACL) (48/79, 61%). Of the 64 patients with treatment information, 31/64 (48%) were managed surgically: 12/31 (39%) had PCL reconstruction, 13/31 (42%) had ACL reconstruction, 10/31 (32%) had posterolateral corner reconstruction, 9/31 (29%) had LCL reconstruction, 8/31 (26%) had meniscectomy, and 8/31 (26%) had fixation of a fracture. Proximal third PCL tear and multiligamentous injury were more commonly associated with surgical management (P < 0.05). Posterolateral and posteromedial corner, ACL, collateral ligament, meniscus, patellar retinaculum, and gastrocnemius muscle injury, and fracture were more likely to result in surgical management (P < 0.05). Patients with high-grade partial/complete PCL tear were more likely to have PCL reconstruction as a portion of surgical management (P < 0.05).Conclusions: Location of PCL tear and presence of other knee injuries were associated with surgical management while high-grade/complete PCL tear grade was associated with PCL reconstruction. MRI reporting of PCL tear location, severity, and of other knee structure injuries is important for guiding clinical management. [ABSTRACT FROM AUTHOR]

This study investigates corrosion of Fe-Ni-based alloy 800H that were exposed to supercritical CO2 (sCO2), ambient air and argon gas at pressures up to 20 MPa, at 650 and 750 °C for up to 1000 h. This alloy and other comparable metal alloys are expected to be used in sCO2 heat exchanger cycles as proposed in the DOE Advanced Ultra-Supercritical program. Alloy 800H is considered for this application, because it meets the high-temperature strength and creep rupture requirements and is a lower cost alternative to other Ni-based alloys. The oxidation performance and microstructural changes due to exposure in sCO2 have been evaluated and compared with exposures in air and Ar. The 800H alloy showed similar oxide scale thicknesses in sCO2 as in air. A recrystallized zone was observed beneath the oxide formed in air and sCO2. No such zone was observed after exposure to Ar, suggesting this recrystallization was associated with the oxidation process and not simply an effect of surface finishing. A wider recrystallized zone was observed underneath the oxide formed in sCO2 than in air. The effect of air and sCO2 on internal oxidation and carburization was investigated as well, showing that air led to more internal oxidation but less internal carburization than sCO2. It was concluded that the carbon species provided by the sCO2 atmosphere in conjunction with the increased grain boundary density in the recrystallized zone allowed for more ingress of carbon into the base metal, which resulted in a higher densities of carbides beneath the oxide scale. [ABSTRACT FROM AUTHOR]

Transected axons fail to regrow across anatomically complete spinal cord injuries (SCI) in adults. Diverse molecules can partially facilitate or attenuate axon growth during development or after injury1-3, but efficient reversal of this regrowth failure remains elusive4. Here we show that three factors that are essential for axon growth during development but are attenuated or lacking in adults—(i) neuron intrinsic growth capacity2,5-9, (ii) growth-supportive substrate10,11 and (iii) chemoattraction12,13—are all individually required and, in combination, are sufficient to stimulate robust axon regrowth across anatomically complete SCI lesions in adult rodents. We reactivated the growth capacity of mature descending propriospinal neurons with osteopontin, insulin-like growth factor 1 and ciliary-derived neurotrophic factor before SCI14,15; induced growth-supportive substrates with fibroblast growth factor 2 and epidermal growth factor; and chemoattracted propriospinal axons with glial-derived neurotrophic factor16,17 delivered via spatially and temporally controlled release from biomaterial depots18,19, placed sequentially after SCI. We show in both mice and rats that providing these three mechanisms in combination, but not individually, stimulated robust propriospinal axon regrowth through astrocyte scar borders and across lesion cores of non-neural tissue that was over 100-fold greater than controls. Stimulated, supported and chemoattracted propriospinal axons regrew a full spinal segment beyond lesion centres, passed well into spared neural tissue, formed terminal-like contacts exhibiting synaptic markers and conveyed a significant return of electrophysiological conduction capacity across lesions. Thus, overcoming the failure of axon regrowth across anatomically complete SCI lesions after maturity required the combined sequential reinstatement of several developmentally essential mechanisms that facilitate axon growth. These findings identify a mechanism-based biological repair strategy for complete SCI lesions that could be suitable to use with rehabilitation models designed to augment the functional recovery of remodelling circuits. Stimulating the intrinsic growth capacity of neurons and providing growth-supportive substrate and chemoattraction can allow axon regrowth across anatomically complete spinal cord injuries in adult rodents. [ABSTRACT FROM AUTHOR]

Tissue-specific autoimmunity occurs when selected antigens presented by susceptible alleles of the major histocompatibility complex are recognized by T cells. However, the reason why certain specific self-antigens dominate the response and are indispensable for triggering autoreactivity is unclear. Spontaneous presentation of insulin is essential for initiating autoimmune type 1 diabetes in non-obese diabetic mice [1], [2]. A major set of pathogenic CD4 T cells specifically recognizes the 12-20 segment of the insulin B-chain (B:12-20), an epitope that is generated from direct presentation of insulin peptides by antigen-presenting cells [3], [4]. These T cells do not respond to antigen-presenting cells that have taken up insulin that, after processing, leads to presentation of a different segment representing a one-residue shift, B:13-21 [4]. CD4 T cells that recognize B:12-20 escape negative selection in the thymus and cause diabetes, whereas those that recognize B:13-21 have only a minor role in autoimmunity [3]- [5]. Although presentation of B:12-20 is evident in the islets [3], [6], insulin-specific germinal centres can be formed in various lymphoid tissues, suggesting that insulin presentation is widespread [7], [8]. Here we use live imaging to document the distribution of insulin recognition by CD4 T cells throughout various lymph nodes. Furthermore, we identify catabolized insulin peptide fragments containing defined pathogenic epitopes in β-cell granules from mice and humans. Upon glucose challenge, these fragments are released into the circulation and are recognized by CD4 T cells, leading to an activation state that results in transcriptional reprogramming and enhanced diabetogenicity. Therefore, a tissue such as pancreatic islets, by releasing catabolized products, imposes a constant threat to self-tolerance. These findings reveal a self-recognition pathway underlying a primary autoantigen and provide a foundation for assessing antigenic targets that precipitate pathogenic outcomes by systemically sensitizing lymphoid tissues. A sensitive T cell tracking assay reveals immunogenic activity of specific catabolized peptide fragments of insulin and their effects on T cell activity in lymph nodes, highlighting communication between pancreatic islets and lymphoid tissue. [ABSTRACT FROM AUTHOR]

Corrosion of alloy 625 was investigated in three supercritical CO2 (sCO2) environments: research-grade (RG) (99.999 pct pure), RG + 100 ppm O2 (at.), and RG + 1 pct CO (at.). Samples were exposed to each condition for a total of 1000 hours at 750 °C and 20 MPa. Each sample was analyzed using mass change, scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), time-of-flight-secondary ion mass spectroscopy (TOF-SIMS), and Raman spectroscopy. Samples exposed to RG CO2 produced a compact uniform chromia layer. The samples exposed to oxygen-rich CO2 showed a less-uniform oxide with nodules characterized by Ni- and Fe-rich oxides on the surface with enhanced chromia formation beneath. The oxide grown in 1 pct CO exhibited the least protective oxide consisting of a duplex chromia scale with inner equiaxed grain structure and an outer porous layer. RG + 1 pct CO was the only environment in which carbon was observed throughout the oxide, although carbon enrichment was observed at the M-O interface of the oxides produced in RG and RG + 1 pct CO environments. A model for explaining carburization of chromium in sCO2 environments was produced by treating the oxide as a diffusion barrier and considering the chemical equilibrium of CO2 through the Cr2O3 phase. [ABSTRACT FROM AUTHOR]

The thymus is responsible for generating a diverse yet self-tolerant pool of T cells. Although the thymic medulla consists mostly of developing and mature AIRE+ epithelial cells, recent evidence has suggested that there is far greater heterogeneity among medullary thymic epithelial cells than was previously thought. Here we describe in detail an epithelial subset that is remarkably similar to peripheral tuft cells that are found at mucosal barriers. Similar to the periphery, thymic tuft cells express the canonical taste transduction pathway and IL-25. However, they are unique in their spatial association with cornified aggregates, ability to present antigens and expression of a broad diversity of taste receptors. Some thymic tuft cells pass through an Aire-expressing stage and depend on a known AIRE-binding partner, HIPK2, for their development. Notably, the taste chemosensory protein TRPM5 is required for their thymic function through which they support the development and polarization of thymic invariant natural killer T cells and act to establish a medullary microenvironment that is enriched in the type 2 cytokine, IL-4. These findings indicate that there is a compartmentalized medullary environment in which differentiation of a minor and highly specialized epithelial subset has a non-redundant role in shaping thymic function. A comprehensive analysis of the thymic medulla identifies a tuft-cell-like thymic epithelial cell population that is necessary for shaping thymic function. [ABSTRACT FROM AUTHOR]

Type 1 diabetes is an autoimmune disease arising from the destruction of pancreatic insulin-producing beta cells. The disease represents a continuum, progressing sequentially at variable rates through identifiable stages prior to the onset of symptoms, through diagnosis and into the critical periods that follow, culminating in a variable depth of beta cell depletion. The ability to identify the very earliest of these presymptomatic stages has provided a setting in which prevention strategies can be trialled, as well as furnishing an unprecedented opportunity to study disease evolution, including intrinsic and extrinsic initiators and drivers. This niche opportunity is occupied by Type 1 Diabetes TrialNet, an international consortium of clinical trial centres that leads the field in intervention and prevention studies, accompanied by deep longitudinal bio-sampling. In this review, we focus on discoveries arising from this unique bioresource, comprising more than 70,000 samples, and outline the processes and science that have led to new biomarkers and mechanistic insights, as well as identifying new challenges and opportunities. We conclude that via integration of clinical trials and mechanistic studies, drawing in clinicians and scientists and developing partnership with industry, TrialNet embodies an enviable and unique working model for understanding a disease that to date has no cure and for designing new therapeutic approaches. [ABSTRACT FROM AUTHOR]

The corrosion of Ni-based alloy Haynes 230 in supercritical carbon dioxide at temperatures of 650 and 750 °C at a pressure of 20 MPa was investigated. In high-purity research grade CO, the corrosion performance of the alloy was excellent with a thin, uniform, protective chromium-rich oxide layer forming on the surface. Introduction of 10 and 100 ppm O impurity in the CO environment noticeably enhanced oxidation with evidence of oxide spallation and nodule formation. In these oxygen impurity added tests, increased oxidation led to subsurface voids due to the more rapid outward diffusion of chromium as well as intergranular alumina and chromia. The oxygen concentration at the inlet and the outlet of the autoclave was measured and used to support the results of characterization of the surface oxide to develop a more holistic understanding of the role of oxygen impurity on the corrosion process. In all cases, there some carbon was observed, which manifested as slightly higher concentration of chromium-carbide phase at the grain boundaries compared to the unexposed alloy. [ABSTRACT FROM AUTHOR]

If sustainability science is to mature as a discipline, it will be important for practitioners to discuss and eventually agree upon the fundamentals of the paradigm on which the new discipline is based. Since sustainability is fundamentally a normative assertion about tradeoffs among values, how society chooses the specifics among these tradeoffs is central to the sustainability problem. Whose values should count in making social decisions and how should the multiplicity of values that exist be known and used in that decision process? Given the vast spatial domains and temporal domains at work in the sustainability problem, we need some means of reconciling the inevitably divergent choices depending on whose values we count, how we know what those values are, and how we count them in making social decisions. We propose an approach to dealing with these questions based on Rawls (A theory of justice. Belknap Press, Cambridge, ) and explore the problems inherent in a social choice theory for sustainability science. [ABSTRACT FROM AUTHOR]

Previous palaeomagnetic studies have allowed the recognition of a distinctive area of Neotethyan oceanic rocks, including the Troodos ophiolite in Cyprus and the Hatay ophiolite to the east in southern Turkey, that underwent 90° of anticlockwise rotation between Late Cretaceous (Campanian) and Early Eocene time. The southern and western boundaries of this rotated Troodos-Hatay microplate have been inferred to lie within, or adjacent to, zones of deformed oceanic and continental margin rocks that are now exposed in southern and western Cyprus; however, the northern boundary of the microplate remains undefined. Relevant to this problem, palaeomagnetic data are presented here from basaltic lavas exposed along the Kyrenia Range, mostly from Late Cretaceous (Maastrichtian) sites and one Eocene site. A positive inclination-only fold test demonstrates that remanences are pre-deformational in age, and positive conglomerate tests show that magnetic remanences were acquired before Late Eocene-Early Oligocene time, together suggesting that primary magnetizations are preserved. Data from the eastern Kyrenia Range and the Karpas Peninsula (the easternmost extension of the Kyrenia Range) document significant relative tectonic rotation between these localities, with no rotation in the eastern range versus 30° of anticlockwise rotation of the Karpas Peninsula. Unfortunately, palaeomagnetic sites from the western Kyrenia Range did not yield tectonically interpretable magnetization directions, probably due to complex poly-phase thrusting and folding, and the central range also yielded no interpretable data. However, the available palaeomagnetic data are sufficient to demonstrate that the Kyrenia terrane underwent a separate rotation history to the Troodos-Hatay microplate and also implies that the northern boundary of the Troodos-Hatay microplate was located between the Troodos ophiolite and the Kyrenia Range. The former microplate margin has since been overridden and concealed by two phases of southwards thrusting and folding of the Kyrenia Range units (Mid-Eocene; latest Miocene-earliest Pliocene). The likely cause of the anticlockwise rotation affecting the Karpas Peninsula, and by implication the curvature of the Kyrenia Range as a whole, relates to regional late-stage subduction and diachronous continental collision. The Southern Neotethys sutured in SE Turkey during the Early Miocene, whereas a relict ocean basin remained further west in the easternmost Mediterranean, allowing a remnant N-dipping subduction zone to retreat southwards and so induce the present-day arcuate shape of the Kyrenia Range. [ABSTRACT FROM AUTHOR]