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Background: Leigh syndrome (LS) is the most frequent paediatric clinical presentation of mitochondrial disease. The clinical phenotype of LS is highly heterogeneous. Though historically the treatment for LS is largely supportive, new treatments are on the horizon. Due to the rarity of LS, large-scale interventional studies are scarce, limiting dissemination of information of therapeutic options to the wider scientific and clinical community. Objective: We conducted a systematic review of pharmacological therapies of LS following the guidelines for FAIR-compliant datasets. Methods: We searched for interventional studies within Clincialtrials.gov and European Clinical trials databases. Randomised controlled trials, observational studies, case reports and case series formed part of a wider MEDLINE search. Results: Of the 1,193 studies initially identified, 157 met our inclusion criteria, of which 104 were carried over into our final analysis. Treatments for LS included very few interventional trials using EPI-743 and cysteamine bitartrate. Wider literature searches identified case series and reports of treatments repleting glutathione stores, reduction of oxidative stress and restoration of oxidative phosphorylation. Conclusions: Though interventional randomised controlled trials have begun for LS, the majority of evidence remains in case reports and case series for a number of treatable genes, encoding cofactors or transporter proteins of the mitochondria. Our findings will form part of the international expert-led Solve-RD efforts to assist clinicians initiating treatments in patients with treatable variants of LS.

Mast cell sarcoma is a rare disease associated with a dismal prognosis. We report a unique case of mast cell sarcoma arising in a patient with a history of T-lymphoblastic leukemia/lymphoma (T-ALL)...

Information on bronchoalveolar lavage (BAL) in patients with COVID-19 is limited, and clinical correlation has not been reported. This study investigated the key features of BAL fluids from COVID-19 patients and assessed their clinical significance. A total of 320 BAL samples from 83 COVID-19 patients and 70 non-COVID-19 patients (27 patients with other respiratory viral infections) were evaluated, including cell count/differential, morphology, flow cytometric immunophenotyping, and immunohistochemistry. The findings were correlated with clinical outcomes. Compared to non-COVID-19 patients, BAL from COVID-19 patients was characterized by significant lymphocytosis (p

Objectives The novel coronavirus, severe acute respiratory syndrome coronavirus 2, causing coronavirus disease 2019 (COVID-19) remains a global health threat and a significant source of human morbidity and mortality. While the virus primarily induces lung injury, it also has been reported to cause hepatic sequelae. Methods We aimed to detect the virus in formalin-fixed tissue blocks and document the liver injury patterns in patients with COVID-19 compared with a control group. Results We were able to detect viral RNA in the bronchioalveolar cell blocks (12/12, 100%) and formalin-fixed, paraffin-embedded tissue of the lung (8/8, 100%) and liver (4/9, 44%) of patients with COVID-19. Although the peak values of the main liver enzymes and bilirubin were higher in the patients with COVID-19 compared with the control group, the differences were not significant. The main histologic findings were minimal to focal mild portal tract chronic inflammation (7/8, 88%, P < .05) and mild focal lobular activity (6/8, 75%, P = .06). Conclusions We found that most patients who died of COVID-19 had evidence of mild focal hepatitis clinically and histologically; however, the virus was detected in less than half of the cases.

The diagnostic criteria for juvenile myelomonocytic leukemia have recently been revised to include clinical findings and RAS-pathway gene mutations per the 2016 World Health Organization Classification of Tumors of Hematopoietic and Lymphoid Tissues. Differing clinical behaviors have been observed in cases with CBL versus other RAS-pathway gene (RAS-p) mutations, notably the patients with CBL mutations can be self-limiting with spontaneous resolution. Additional clinical characteristics and histopathologic findings between these subsets are less well-described. We performed a retrospective search and identified cases with either CBL or RAS-p mutations, as per targeted and/or massively parallel sequencing. Eight patients had sufficient material for review, including cytogenetic studies and peripheral blood, bone marrow aspirate, and/or biopsy with flow cytometry analyses. Three patients showed CBL mutations and lower percentages of hemoglobin F and peripheral blood absolute monocyte counts, lesser degrees of leukocytosis compared with the RAS-p cohort, and normal megakaryocyte morphology and myeloblast immunophenotypes. Two of these patients were managed with observation only and experienced resolution of their disease. The patients with RAS-p mutations had severe thrombocytopenia, moderate to severe anemia, and experienced variable clinical outcomes. Abnormal megakaryocyte morphology and decreased numbers of megakaryocytes were seen in cases with RAS-p mutations. In addition, 3 of 4 cases with flow cytometry data demonstrated aberrant CD7 expression in myeloblasts. Our study is the first to identify morphologic and immunophenotypic differences between juvenile myelomonocytic leukemia cases with CBL or RAS-p mutations, and further supports previous reports of significantly different clinical behaviors between these subsets of patients.

Left ventricular assist devices (LVADs) have revolutionized the care of patients with advanced heart failure, yet still require concomitant medications in order to achieve the best possible clinical outcomes. Since the outset of routine placement of durable, continuous-flow LVADs, much of the medication management of these patients to date has been based on International Society of Heart and Lung Transplantation (ISHLT) guidance, most recently published in 2013. Since 2013, numerous multidisciplinary pharmacotherapy publications have increased the LVAD community's understanding of best practices with respect to medications. We identified the major domains of LVAD medication management and conducted a comprehensive search of US National Library of Medicine MEDLINE ® database using keywords chosen to identify medication-related publications of significance dated 2013 or later. Trials pertaining to the HeartMate IITM and the HeartMateTM 3 LVADs (Abbott, Chicago IL) and the HeartWareTM HVADTM System (Medtronic, Minneapolis MN) were chosen for inclusion. Highest priority for inclusion was given to prospective, randomized, controlled studies. Absent these, controlled trials (retrospective or prospective observational) were given next-highest consideration, followed by retrospective uncontrolled studies, and finally case series. Reference lists of qualified publications were reviewed to find any other publications of interest that were not discovered on initial search. Case reports were generally excluded, except where the insight gained was deemed to be uniquely pertinent. This document serves to provide a comprehensive review of the current understanding of optimal medication management in patients with durable, continuous-flow LVADs.

Objectives To determine maternal vs fetal origin for blood in placental intervillous thrombi (IVTs). Methods We used comparative analysis of microsatellites (short tandem repeats [STRs]), sex chromosome fluorescence in situ hybridization (FISH), and immunohistochemistry (IHC) for fetal (ɑ-fetoprotein [AFP]) and maternal (immunoglobulin M [IgM]) serum proteins to distinguish the origin of IVTs. Using an informatics approach, we tested the association between IVTs and fetomaternal hemorrhage (FMH). Results In 9 of 10 cases, the preponderance of evidence showed that the thrombus was mostly or entirely maternal in origin. In 1 case, the thrombus was of mixed origins. STR testing was prone to contamination by entrapped fetal villi. FISH was useful but limited only to cases with male fetuses. IgM showed stronger staining than AFP in 9 cases, supporting maternal origin. By informatics, we found no association between IVTs and FMH. Conclusions Evidence supports a maternal origin for blood in IVTs. IHC for IgM and AFP may be clinically useful in determining maternal vs fetal contribution to IVTs.

Sinonasal glomangiopericytoma (SNGP) is a neoplasm arising in the nasal cavity and paranasal sinuses that shows perivascular myoid differentiation. The diagnosis of SNGP may be diagnostically challenging due to a large number of potential mimics. In the present study, we sought to characterize the histological and molecular features of six cases of SNGP found in prior surgical pathology records over a 15-year period. The average age at diagnosis was 48.5 years (range: 31-78 years), and the male-to-female ratio was 1:1. Imaging studies in all six cases demonstrated avidly enhancing, lobulated soft tissue masses in the nasal cavity, extending into the sinuses and nasopharynx. Histologically, the tumors were unencapsulated and composed of a proliferation of closely packed, bland, and uniform spindle cells growing deep to an intact surface respiratory epithelium. The cells were separated by a distinctive vascular network ranging from capillaries to large vascular spaces. All cases demonstrated strong positivity for smooth muscle actin, cyclin D1, CD99, and β-catenin (100%). Targeted sequencing revealed recurrent CTNNB1 missense mutations in all cases tested. Additionally, TLE1 was positive in all cases which has not been previously reported. No tested cases harbored SS18 translocations. We found that while no single marker resolves immunohistochemical overlap between SNGP and its histologic mimics, an extended immunohistochemical panel that includes β-catenin, cyclin D1, STAT6, smooth muscle actin, pan-cytokeratin cocktails, S100, and SOX10 helps to support the diagnosis of SNGP in diagnostically challenging cases without the need for molecular studies.

Objective 1.) Describe demographic and clinical characteristics of pediatric nasal septal perforations (NSP), 2.) Analyze efficacy of treatment modalities in symptom management and resolution of pediatric NSP, 3.) Describe the surgical technique of external rhinoplasty with vascularized nasal septal flaps in the treatment of nasal septal perforations. Methods IRB-approved retrospective chart review of pediatric patients ages 0–18 years with nasal septal perforations treated at a tertiary care pediatric otolaryngology practice. Demographic and clinical characteristics including gender, age, race, and presenting symptoms, and location, size, and etiology of perforation were collected. Outcomes including persistence of perforation and symptoms at 1 year and most recent visit were recorded. A total of 20 patients were included. Statistical analysis used Fisher's t-test for categorical variables and Wilcoxon rank-sum for continuous variables. Results Median age was 167.5 months (1.5–221.0). The most common etiology was iatrogenic (40%), followed by button battery (20%). Thirty percent of patients underwent surgical repair. Fifty percent of patients who underwent surgical repair achieved closure of their perforation at most recent follow up. Conclusion Pediatric NSP is a challenging issue with limited literature to date. Iatrogenic causes (40%) and button batteries (20%) were the most common etiologies of nasal septal perforation in our study. We introduce an advancement in our center's surgical technique with a case illustration with repair via external rhinoplasty and bilateral vascularized nasal septal flaps. Future larger studies may further elucidate characteristics and treatment modalities associated with successful closure.

Congenital Central Hypoventilation Syndrome (CCHS) is a rare disease characterized by autonomic nervous system dysregulation. Central hypoventilation is the most prominent and clinically important presentation. CCHS is caused by mutations in paired-like homeobox 2b (PHOX2B) and is inherited in an autosomal dominant pattern. A co-occurrence of two asymptomatic PHOX2B variants with a classical CCHS presentation highlights the importance of clinical PHOX2B testing in parents and family members of all CCHS probands. Despite being an autosomal dominant disease, once a polyalanine repeat expansion mutation has been identified, sequencing of the other allele should also be considered.

Published risk stratification models of solitary fibrous tumor (SFT) have been associated with distant metastases outside the central nervous system (CNS), but have not been studied for tumors occurring in the CNS. In a retrospective review, we identified 72 cases of solitary fibrous tumor or hemangiopericytoma (HPC) diagnosed between January 2011 and December 2020 at our institution. The tumors involved the central nervous system (N = 17), thoracic cavity (N = 28), and extrathoracic sites (N = 27). The risk of local recurrence, distant metastasis, or death at 5 years was 57% (95% CI 23%, 76%) in the CNS, 24% (95% CI 2%, 41%) in the thoracic cavity, and 13% (95% CI 0%, 25%) in extrathoracic sites. By contrast, the risk of distant metastasis or death at 5 years was 13% (95% CI 0%, 29%) in CNS primaries, 5% (95% CI 0%, 14%) in thoracic primaries, and 14% (95% CI 0%, 27%) in extrathoracic primaries. Using the published 3- and 4-variable risk stratification models by Demicco et al., we retrospectively assessed our cases for risk of local recurrence, distant metastasis, and death. For tumors outside the CNS, we show that three- and four-variable risk stratification models were associated with recurrence-free survival in addition to the previously known association with distant metastasis (all P 0.05). In contrast, inside the CNS, we show that neither risk model is a significantly associated with clinical behavior, and that WHO grade is likely the best available prognostic tool, though none of the differences were significant. The lack of significant differences can be likely explained by the younger median age (47 years vs 61 years) and smaller median tumor size (3.5 cm vs 5.6 cm), downgrading the risk stratification scores in CNS compared to non-CNS primaries. In conclusion, existing risk stratification models of SFT are not associated with clinical behavior for tumors arising inside the CNS, but are associated with local recurrence in addition to distant metastasis outside the CNS.

Sleep is crucial for optimal well-being, and sex differences in sleep quality have significant implications for women’s health. We review the current literature on sex differences in sleep, such as differences in objective and subjective sleep measures and their relationship with aging. We then discuss the convincing evidence for the role of ovarian hormones in regulating female sleep, and survey how these hormones act on a multitude of brain regions and neurochemicals to impact sleep. Lastly, we identify several important areas in need of future research to narrow the knowledge gap and improve the health of women and other understudied populations.

Background We present a yet to be described association of SARS-CoV-2 infection with Kikuchi-Fujimoto disease. Case presentation A 32-year-old physician with history of SARS-CoV-2 infection presented to the emergency department with 2 weeks of fever, chills, and right sided cervical lymphadenopathy. He was treated empirically for presumed folliculitis with worsening of symptoms leading to repeat presentation to the emergency department. Extensive workup was unrevealing of an infectious cause and needle biopsy of the lesion was unrevealing. An excisional lymph node biopsy revealed follicular hyperplasia with necrotic foci showing abundance of histiocytes at the edge of necrosis with CD8 predominance of T-cells. Final diagnosis was deemed to be Kikuchi-Fujimoto disease. Antibiotic therapy was discontinued, and the patient’s symptoms resolved with steroid therapy and expectant management. Conclusions This is the first report of a patient developing Kikuchi-Fujimoto disease following SARS-CoV-2 infection. Clinicians should be aware of Kikuchi-Fujimoto disease as a possibility when approaching patients with hyper-inflammatory states who present with cervical lymphadenopathy.

International audience; Background: Hereditary peripheral neuropathies are inherited disorders affecting the peripheral nervous system, including Charcot-Marie-Tooth disease, familial amyloid polyneuropathy and hereditary sensory and motor neuropathies. While the molecular basis of hereditary peripheral neuropathies has been extensively researched, interventional trials of pharmacological therapies are lacking. Objective: We collated evidence for the effectiveness of pharmacological and gene-based treatments for hereditary peripheral neuropathies. Methods: We searched several databases for randomised controlled trials (RCT), observational studies and case reports of therapies in hereditary peripheral neuropathies. Two investigators extracted and analysed the data independently, assessing study quality using the Oxford Centre for Evidence Based Medicine 2011 Levels of Evidence in conjunction with the Jadad scale. Results: Of the 2046 studies initially identified, 119 trials met our inclusion criteria, of which only 36 were carried over into our final analysis. Ascorbic acid was shown to have no therapeutic benefit in CMT1A, while a combination of baclofen, naltrexone and sorbitol (PXT3003) demonstrated some efficacy, but phase III data are incomplete. In TTR-related amyloid polyneuropathy tafamidis, patisiran, inotersen and revusiran showed significant benefit in high quality RCTs. Smaller studies showed the efficacy of L-serine for SPTLC1-related hereditary sensory neuropathy, riboflavin for Brown-Vialetto-Van Laere syndrome (SLC52A2/3) and phytanic acid-poor diet in Refsum disease (PHYH). Conclusions: The 'treatable' variants highlighted in this project will be flagged in the treatabolome database to alert clinicians at the time of the diagnosis and enable timely treatment of patients with hereditary peripheral neuropathies.

Negative, or complementary afterimages are experienced following brief adaptation to chromatic or achromatic stimuli, and are believed to be formed in the post-receptoral layers of the retinae. Afterimages can be cancelled by the addition of real images, suggesting that afterimages and real images are processed by similar mechanisms. However given their retinal origin, afterimage signals represented at the cortical level might have different spatio-temporal properties from their real images counterparts. To test this we determined whether afterimages reduce the contrast threshold of added real images, i.e. produce the classic “dipper” function characteristic of contrast discrimination, a behavior believed to be cortically mediated. Stimuli were chromatic and achromatic disks on a grey background. Observers adapted for 1.0 s to two side-by-side disks of a particular color. Following stimulus offset, a test disk added to one side was ramped downwards for 1.5 s to approximately match the temporal characteristic of the afterimage, and the observer was required to indicate the side containing the test disk. The test hue/brightness was either the same as that of the afterimage or a different hue/brightness. The independent variable was the contrast of the adaptor. A dipper followed by masking was observed in most conditions in which the afterimage and test colors had the same hue or brightness. We conclude that afterimages are represented similarly to their real image counterparts at the cortical level.

Over the past few decades, the measurement precision of some pulsar-timing experiments has advanced from ~10 us to ~10 ns, revealing many subtle phenomena. Such high precision demands both careful data handling and sophisticated timing models to avoid systematic error. To achieve these goals, we present PINT (PINT Is Not Tempo3), a high-precision Python pulsar timing data analysis package, which is hosted on GitHub and available on Python Package Index (PyPI) as pint-pulsar. PINT is well-tested, validated, object-oriented, and modular, enabling interactive data analysis and providing an extensible and flexible development platform for timing applications. It utilizes well-debugged public Python packages (e.g., the NumPy and Astropy libraries) and modern software development schemes (e.g., version control and efficient development with git and GitHub) and a continually expanding test suite for improved reliability, accuracy, and reproducibility. PINT is developed and implemented without referring to, copying, or transcribing the code from other traditional pulsar timing software packages (e.g., TEMPO and TEMPO2) and therefore provides a robust tool for cross-checking timing analyses and simulating pulse arrival times. In this paper, we describe the design, usage, and validation of PINT, and we compare timing results between it and TEMPO and TEMPO2., Comment: Re-submitted to the Astrophysical Journal at December 31st, 2020

Three experiments examined whether second-order conditioning resulted in the formation of a fully-featured temporal map, as proposed by the temporal coding hypothesis. Experiments 1 and 2 examined second-order conditioning with different first- and second-order relationships. Measures of the strength of second-order conditioning were mostly consistent with the temporal coding hypothesis; second-order conditioning was best with arrangements in which CS2 occurred prior to the time that the US normally occurred during CS1-US presentations. However, there was no evidence of anticipatory timing during CS2 during second-order conditioning. A third experiment directly examined whether a fully-featured temporal map was formed during second-order conditioning by examining the acquisition of anticipatory timing in subsequent reinforced second-order trials. The results of Experiment 3 suggested that the effects obtained in Experiments 1 and 2 were due to learning of the temporal order and coincidence of events that resulted in the formation of an ordinal temporal map, but that precise durations were not encoded.

Context.— Melanotic schwannoma (MS) is a nerve sheath tumor with a uniform composition of variably melanin-producing Schwann cells and metastatic potential. The MS is an uncommon neoplasm, accounting for less than 1% of all nerve sheath tumors, with a predilection for spinal nerve involvement. Microscopically, the tumors are characterized by spindle and epithelioid cells arranged in interlacing fascicles, with marked accumulation of melanin in neoplastic cells and associated melanophages. The MSs are frequently associated with Carney complex, showing features of psammoma bodies and adipose-like cells. Strict criteria of malignancy in MS are not well developed, although a combination of worrisome histologic features (large, vesicular nuclei, with macronucleoli, brisk mitotic activity, and necrosis) raises concern for aggressive behavior. Objective.— To review the current status of the MS literature, discussing putative etiology, histopathology, current genetics, and differential diagnoses, including overlap with other pigmented tumors. Data Sources.— Search of PubMed (National Center for Biotechnology Information, Bethesda, Maryland) and the authors' own experiences. Conclusions.— The occurrence of MS at several unusual anatomic sites and its spectrum of morphologic patterns can result in significant diagnostic difficulty, and correct diagnosis is particularly important because of its high tendency to recur locally and to metastasize, which highlights the importance of diagnostic recognition, ancillary molecular genetic testing, and close clinical follow-up of patients with MS.

When individuals face risks, they seek information to reduce uncertainty. This study examines where people turn for information and the effects this information seeking has on belief and be...

Context.— Detection of acquired variants in cancer is a paradigm of precision medicine, yet little has been reported about clinical laboratory practices across a broad range of laboratories. Objective.— To use College of American Pathologists proficiency testing survey results to report on the results from surveys on next-generation sequencing–based oncology testing practices. Design.— College of American Pathologists proficiency testing survey results from more than 250 laboratories currently performing molecular oncology testing were used to determine laboratory trends in next-generation sequencing–based oncology testing. Results.— These presented data provide key information about the number of laboratories that currently offer or are planning to offer next-generation sequencing–based oncology testing. Furthermore, we present data from 60 laboratories performing next-generation sequencing–based oncology testing regarding specimen requirements and assay characteristics. The findings indicate that most laboratories are performing tumor-only targeted sequencing to detect single-nucleotide variants and small insertions and deletions, using desktop sequencers and predesigned commercial kits. Despite these trends, a diversity of approaches to testing exists. Conclusions.— This information should be useful to further inform a variety of topics, including national discussions involving clinical laboratory quality systems, regulation and oversight of next-generation sequencing–based oncology testing, and precision oncology efforts in a data-driven manner.

Malignant ectomesenchymoma is a rare pediatric neoplasm with dual mesenchymal and neuroectodermal elements. Mesenchymal component is usually rhabdomyosarcoma, particularly embryonal subtype, whereas neuroectodermal derivatives are frequently a neuroblastic tumor. Ectomesenchymoma manifests in various sites given the wide migration of neural crest cells during development, though the pelvis/perineum is most often involved. Moreover, no unique unifying molecular abnormality has been determined.We conducted a retrospective study to analyze the spectrum of ectomesenchymal tumors encountered in our pediatric population. Six patients were identified and data pertaining to patients' demographic, tumor size and site, histologic components with immunophenotypic profile, molecular alterations, treatment, and outcome were collected.Mesenchymal elements, represented by rhabdomyosarcoma in all instances, were the dominant component in the majority of cases (5/6). Embryonal and alveolar morphology had similar distribution (3/6) and all patients with alveolar subtype harbored the characteristic translocations of this entity. The neuroectodermal component was most often a neuroblastic-like neoplasm (4/6); however, 2/6 cases demonstrated primitive neuroectodermal tumor-like morphology. No unifying alterations were found on molecular studies.Our analysis extends the histologic and molecular spectrum of these tumors and highlights their heterogeneity. The percentage of cases with alveolar rhabdomyosarcoma or primitive neuroectodermal-like tumor components suggests that these types of elements might be underreported. This study is also the first to demonstrate FOXO1 gene rearrangements in malignant ectomesenchymoma with alveolar rhabdomyosarcoma subtype.

Specialised DDH (developmental dysplasion of the hip) clinics are developing around Ireland but are, however, variable in how they are operated. A DDH clinic was set up in the South-east of Ireland in 2002 with the goal of achieving an integrated care pathway between the orthopaedic surgical team and nursing team, working to an explicit protocol while also fostering a strong collaboration with the ultrasound department. This paper aims to explore the effectiveness of this dedicated clinic in the Southeast of Ireland.

In this study, we assess the extent to which attending a candidate rally was associated with distrust of democratic institutions, epistemic rigidity, attribution of malevolent intentions to the political outgroup, and acceptance of political violence. Surveys ( N = 251) were distributed at rallies the night before and day of the 2016 Iowa Caucuses. Results suggest that attendees of rallies for Bernie Sanders or Donald Trump were more likely to distrust democracy relative to attendees of a Hillary Clinton or Ted Cruz rally. Findings also suggest that mistrust of democracy was associated with greater attribution of malevolence and acceptance of political violence. Attending a Sanders or Trump rally was indirectly associated with attribution of malevolence and acceptance of political violence through democratic mistrust.

Researchers have noted that an individual’s processing of political media messages occurs through various filters including partisanship, interest, and cynicism. The phenomenon of motivated processing, however, is understudied particularly in the context of televised presidential debates. As major campaign events, presidential debates have been linked to increases in viewers’ political knowledge, political information efficacy, and changes in candidate evaluation. Yet individual’s information processing, largely unexplored in the extant debate literature, may well influence these outcomes. In the present study, we manipulate processing of a political debate and monitor the effects through participant engagement with social media. Researchers asked debate viewers to tweet while watching 2016 Democrat and Republican presidential primary debates following instructions designed to prime either directional motivated processing or accuracy motivated processing. The results demonstrate that the accuracy prompt reduced issue-based tweeting and therefore reduced knowledge acquisition. Conversely, the directional prompt increased issue-based tweeting and therefore increased knowledge acquisition.

To improve nondestructive evaluation (NDE), the dependences of acoustic emission testing were investigated. Acoustic emission testing, is a technique in the NDE field that has multiple different advantages. Its versatility allows engineers and other researchers to detect and monitor flaws and discontinuities within different materials. This report will describe how acoustic emission (AE) testing is being used to monitor materials such as metal, concrete, composites, polymers, and wood. This will be done by explaining a brief theory and provide examples of AE and how it’s applied to different materials. NDE is an important field within engineering because it evaluates complex components of a system and provides data related to the health of these components without damaging them. This paper describes in detail the AE detection and verification process in order to give some references for the industry counterparts, while promoting the development of the AE technology.

Copyright 2019 The Authors. Patterns in the two eyes' views that are not identical in hue or contrast often elicit an impression of luster, providing a cue for discriminating them from perfectly matched patterns. Here we attempt to determine the mechanisms for detecting interocular differences in luminance contrast, in particular in relation to the possible contributions of binocular differencing and binocular summing channels. Test patterns were horizontally oriented multi-spatial-frequency luminance-grating patterns subject to variable amounts of interocular difference in grating phase, resulting in varying degrees of local interocular contrast difference. Two types of experiment were conducted. In the first, subjects discriminated between a pedestal with an interocular difference that ranged upward from zero (i.e., binocularly correlated) and a test pattern that contained a bigger interocular difference. In the second type of experiment, subjects discriminated between a pedestal with an interocular difference that ranged downward from a maximum (i.e., binocularly anticorrelated) and a test pattern that contained smaller interocular difference. The two types of task could be mediated by a binocular differencing and a binocular summing channel, respectively. However, we found that the results from both experiments were well described by a simpler model in which a single, linear binocular differencing channel is followed by a standard nonlinear transducer that is expansive for small signals but strongly compressive for large ones. Possible reasons for the lack of involvement of a binocular summing channel are discussed in the context of a model that incorporates the responses of both monocular and binocular channels. This work was funded by a Canadian Institute of Health Research grant (MOP 123349) to FAAK and a Leverhulme Trust grant (EM-2017-097) to MAG.

T-cell therapy-related acute lymphoblastic leukemia (T-t-ALL) is a rare condition associated with previous cytotoxic therapy for another disease. Here we report T-t-ALL with inv(11)(q21q23), which involves KMT2A and MAML2, a transcriptional coactivator of NOTCH proteins, that occurred after chemotherapy for Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia. This case describes the youngest patient with T-t-ALL harboring inv(11)(q21q23) and is the first independent report following an initial series also occurring in children. Our results lend further support to the observation that the KMT2A-MAML2 fusion gene resulting from inv(11)(q21q23) is likely a recurrent cytogenetic abnormality in T-t-ALL and appears to be associated with pediatric cases.

As individuals turn to social media sites for health information, it is important to understand the factors that influence their perceptions of this information. This study employed an experiment to investigate the impact of social media discussion on perceptions of vaccines. Analysis, using structural equation modeling, revealed that source credibility and the civility of a discussion indirectly influence policy support requiring vaccinations, intention to vaccinate future children, and willingness to engage in discussion about vaccines. This impact is mediated by message elaboration and attitudes of the value of vaccinations. As individuals think about a pro-vaccine message and understand the importance of receiving vaccinations, they are more likely to engage in pro-social vaccination choices.

Object recognition is a type of perception that enables observers to recognize familiar shapes and categorize them into real-world identities. In this preregistered study, we aimed to determine whether pupil size changes occur during the perception and recognition of identifiable objects. We compared pupil size changes for familiar objects, nonobjects, and random noise. Nonobjects and noise produced greater pupil dilation than familiar objects. Contrary to previous evidence showing greater pupil dilation to stimuli with more perceptual and affective content, these results indicate a greater pupil dilation to stimuli that are unidentifiable. This is consistent with the relative salience of novelty compared to familiarity at the physiological level driving the pupil response. FRQNT Fellowship; Joseph-Armand Bombardier Scholarship from the Social Sciences and Humanities Research Council of Canada; Canadian Institute of Health Research grant

Introduction Malignant pleural mesothelioma (MPM) is a rare but highly aggressive malignancy most often associated with exposure to asbestos. Recent evidence points to oestrogen receptor (ER)-β having a tumour-suppressor role in MPM progression, and this raises the question of whether selective modulators of ERs could play a role in augmenting MPM therapy. Materials and methods We investigated the action of tamoxifen in inhibiting the growth and modulating the cisplatin sensitivity of four MPM cell lines. Results Tamoxifen inhibited the growth of MPM cells and also modulated their sensitivity to cisplatin. The MPM cell lines expressed ERβ, but the actions of tamoxifen were not blocked by antagonism of nuclear ERs. Tamoxifen treatment repressed the expression of cyclins by MPM cells, resulting in cell-cycle arrest and caspase-3-coupled apoptosis signaling. Conclusion The ER-independent actions of tamoxifen on MPM cell proliferation and cell-cycle progression may have clinical benefits for a subset of patients with MPM.

This study employs a rhetorical analysis of Planned Parenthood’s rhetoric in response to the crisis emerging from the release of controversial videos by the Center for Medical Progress. Using Bostdorff and Vibbert’s concept of values advocacy and Heath’s discussion of external rhetoric, we examine how Planned Parenthood appeals to core American values through social media in order to enhance its image and reinforce its legitimacy. The values of truth, health, agency, education, unity, and equality are ubiquitous throughout Planned Parenthood’s strategic communication with the public. This research contributes to ongoing academic discussions of the theoretical and practical implications of external rhetoric, values advocacy, and legitimacy in public relations.

Purpose The goal of this study was to analyze the association of copy number gain of 1q in favorable-histology Wilms tumors (FHWTs) with event-free survival (EFS) and overall survival (OS) within each tumor stage and with 1p and 16q copy number loss and/or loss of heterozygosity. Methods Unilateral FHWTs from 1,114 patients enrolled in National Wilms Tumor Study-5 that were informative for 1p and 16q microsatellite markers (previously determined) and informative for 1q gain, 1p loss, and 16q loss using multiplex ligation-dependent probe amplification were analyzed. Results Eight-year EFS was 86% (95% CI, 84% to 88%) for the entire cohort. Of 1,114 patients, 317 tumors (28%) displayed 1q gain. Eight-year EFS was 77% for those with 1q gain and 90% for those lacking 1q gain (P < .001). Eight-year OS was 88% for those with 1q gain and 96% for those lacking 1q gain (P < .001). Within each disease stage, 1q gain was associated with inferior EFS (stage I, 85% v 95%; P = .0052; stage II, 81% v 87%; P = .0775; stage III, 79% v 89%; P = .01; stage IV, 64% v 91%; P = .001). OS was significantly inferior in patients with stage I (P < .0015) and stage IV disease (P = .011). With multivariable analysis, 1q gain was associated with an increased relative risk of relapse of 2.4 (P < .001), whereas 1p loss was not, despite significance on univariable analysis. Conclusion Gain of 1q is associated with inferior survival in unilateral FHWTs and may be used to guide risk stratification in future studies.

Key points Patients in intensive care experience distress because of a multitude of factors and a significant proportion is attributable to pain.1 A vast majority of patients report moderate to severe pain at some point during their intensive care stay. Pain can be caused or provoked by many pre-existing conditions: acute medical, surgical, or routine aspects of intensive care (Table 1). View this table: Table 1 Causes of pain in intensive care. SCI, spinal cord injuries; GBS, Guillain-Barre syndrome; MS, multiple sclerosis Pain is widely regarded as the fifth vital sign, and it induces a myriad of deleterious physiological changes in most organ systems. Severe pain induces a stress response and sympatho-adrenergic stimulation causing tachycardia, hypertension, increased myocardial oxygen consumption, and can induce myocardial ischaemia in susceptible patients. Poorly managed pain from abdominal incisions reduces diaphragmatic function, causes hyperventilation and atelectasis. Pain especially in sedated patients can present as agitation, delirium and when badly managed can have psychological sequelae like post-traumatic stress disorder,2 depression, and anxiety or it can progress to chronic pain. Systemic deleterious effects of pain include systemic inflammatory response syndrome, hyperglycaemia, immunosuppression, impaired wound healing, hypercoagulability, and increased catabolism. All these detrimental effects can …

Sandwich-structured composites are in high demand in various industries, and additive manufacturing has proven its ability to meet this demand. As a result of the advances in three-dimensional (3D) printing techniques, 3D-printed polymers have received considerable attention in fabrication of sandwich structures with complex geometries. This paper is concerned with design, manufacturing, and analysis of the 3D-printed sandwich-structured components which experienced various loadings and environmental conditions. The core structure plays a major role in the in-plane behavior of lattice composites, therefore in this study, sandwich specimens with two types of core topologies made of two common and similar 3D printing filaments, acrylonitrile butadiene styrene (ABS) and acrylonitrile styrene acrylate (ASA), were manufactured. Based on the applications of sandwich-structured parts, they might experience different temperatures in their service life. In order to determine effects of thermal environment, we conducted accelerated thermal aging within temperatures of 22-60 ° C , which is below glass temperature of the examined materials. Based on a series of three-point bending tests, the failure behavior of the original and aged components are determined, and the effects of temperature change on the bending behavior of 3D-printed sandwich parts are discussed. The experimental practice revealed that ASA with honeycomb core specimens indicated highest stability under bending load after thermal aging. The current study sheds lights on durability of 3D-printed sandwich structural elements, and the obtained results demonstrate feasibility of 3D printing technology in fabrication of thermal-stable sandwich structures.

Despite the complexity of the visual world, humans rarely confuse variations in illumination, for example shadows, from variations in material properties, such as paint or stain. This ability to distinguish illumination from material edges is crucial for determining the spatial layout of objects and surfaces in natural scenes. In this study, we explore the role that color (chromatic) cues play in edge classification. We conducted a psychophysical experiment that required subjects to classify edges into illumination and material, in patches taken from images of natural scenes that either contained or did not contain color information. The edge images were of various sizes and were pre-classified into illumination and material, based on inspection of the edge in the context of the whole image from which the edge was extracted. Edge classification performance was found to be superior for the color compared to grayscale images, in keeping with color acting as a cue for edge classification. We defined machine observers sensitive to simple image properties and found that they too classified the edges better with color information, although they failed to capture the effect of image size observed in the psychophysical experiment. Our findings are consistent with previous work suggesting that color information facilitates the identification of material properties, transparency, shadows and the perception of shape-from-shading., Author summary Our visual environment contains both luminance and color (chromatic) information. Understanding the role that each plays in our visual perception of natural scenes is a continuing topic of investigation. In this study, we explore the role that color cues play in a specific task: edge classification. We conducted a psychophysical experiment that required subjects to classify edges as « shadow » or « other », depending on whether or not the images contained color information. We found edge classification performance to be superior for the color compared to grayscale images. We also defined machine observers sensitive to simple image properties and found that they too classified the edges better with color information. Our results show that color acts as a cue for edge classification in images of natural scenes.

Background Renal cell carcinomas (RCCs) are rare in young patients. Knowledge of their pathologic and molecular spectrum remains limited, and no prospective studies have been performed to date in this population. This study analyzes patients diagnosed with RCC who were prospectively enrolled in the AREN03B2 Children's Oncology Group (COG). The objective was to classify these tumors with the aid of focused genetic testing and to characterize their features. Methods All tumors registered as RCC by central review were retrospectively re-reviewed and underwent additional ancillary studies. Tumors were classified according to the 2016 World Health Organization classification system when possible. Results In total, 212 tumors were identified, and these were classified as microphthalmia transcription factor (MiT) translocation RCC (MiT-RCC) (41.5%), papillary RCC (16.5%), renal medullary carcinoma (12.3%), chromophobe RCC (6.6%), clear cell RCC (3.3%), fumarate hydratase-deficient RCC (1.4%), and succinate dehydrogenase-deficient RCC (0.5%). Other subtypes included tuberous sclerosis-associated RCC (4.2%), anaplastic lymphoma kinase (ALK)-rearranged RCC (3.8%), thyroid-like RCC (1.4%), myoepithelial carcinoma (0.9%), and unclassified (7.5%). MiT-RCCs were classified as either transcription factor E3 (TFE3) (93.2%) or EB (TFEB) (6.8%) translocations, and characterization of fusion partners was possible in most tumors. Conclusions The current study delineates the frequency of distinct RCC subtypes in a large prospective series of young patients and contributes knowledge to the diagnostic, clinical, and genetic features of MiT-RCC, the most common subtype among this age group. The identification of rare subtypes expands the spectrum of RCC in young patients, supporting the need for a thorough diagnostic workup. These studies may aid in the introduction of specific therapies for different RCC subtypes in the future. Cancer 2018. © 2018 American Cancer Society.

Many Aboriginal and Torres Strait Islander people live in urban areas, but epidemiological data about their health status and health needs are lacking. This knowledge is critical to informing and evaluating initiatives to improve service delivery and health outcomes. One potential data source is de-identified routinely collected clinical data. This cross-sectional study, conducted in an urban Aboriginal and Torres Strait Islander primary healthcare service, involved randomly selecting a sample of 400 patients aged ≥15 years, and manually extracting electronic health record data. In the sample, 49% of patients were aged

Introduction Inpatient bed pressures in the NHS mean that ambulatory service development is needed. Day case and short stay units developed for elective surgery in our trust were not suited to the needs of patients with liver disease. Services managed through semi-acute pathways Resulted in unpredictable waiting times, unplanned admissions and poor patient experience. Following a pilot project in 2016–17, we describe the 2nd phase in implementing ambulatory care services utilising a re-commissioned 4 bed ward bay in a large liver centre. Primary aims were admission avoidance (AA) and inpatient bed day savings. Secondary aims were to achieve >70% occupancy, deliver excellent patient experience, provide facilities for earlier discharge (ED). Methods We identified initial criteria for service delivery through a specialist nurse led unit. Patient episodes were coded to identify procedures, infusion treatments and AA/ED attendances. Safety was assessed by procedure complication rates and patient readmission rates. We used Survey Monkey® to assess patient experience. Bed savings were identified from historical length of stay data in 2015–16. Results Between 1 st May–31 st Dec 2017 there were 705 attendances. Of these: 371 large volume paracentesis, 49 urgent liver biopsy, 80 infusions, 46 ascites follow-up and 159 AA/ED indications. Based on a 2.5 day admission for paracentesis, 927 inpatient bed days were saved for this indication and at least 420 urgent, semi-acute or unplanned admissions were avoided. Utilisation increased from 68 attendances/month to 115 in Dec 2017. The unit reached 70% occupancy at 3 months. By Dec 2017 occupancy was >90%. There were 3 readmissions and 1procedure complication. 95% of patients thought that explanations regarding procedure were very clear and 95% that they were well informed throughout the day. 95% would recommend the service to friends and family. Conclusion A clear benefit to patients and the service was seen during the first 6 months of opening this unit. We continue to identify indications for use. Other benefits include a growing list of clear admission avoidance/early discharge for other indications. Bed day release has helped patient flow for admissions. Costs incurred in developing a specialist nursing team are offset by their other roles and transfer of ward nursing costs. Unpredicted benefits include a contribution to an overall improvement in ward quality metrics, and release of junior doctor time to direct inpatient management.

Patterns in the two eyes' views that are not identical in hue or contrast often elicit an impression of luster, providing a cue for discriminating them from perfectly matched patterns. Here we ask whether the mechanism for detecting interocular differences (IDs) is adaptable. Our stimuli were horizontally oriented multispatial-frequency grating patterns that could be subject to varying degrees of ID through the introduction of interocular phase differences in the grating components. Subjects adapted to patterns that were either correlated, uncorrelated, monocular (one eye only), or anticorrelated. Following adaptation, thresholds for detecting IDs were measured using a staircase procedure. It was found that ID thresholds were elevated following adaptation to uncorrelated, monocular, and anticorrelated but not correlated patterns. Threshold elevation was found to be maximal when the orientations of the adaptor and test gratings were the same, and when their spatial frequencies were similar. The results support the existence of a specialized mechanism for detecting IDs, the most likely candidate being the binocular differencing channel proposed in previous studies. Canadian Institute of Health Research

Purpose: For a given bowtie filter design, both the selection of material and the physical design control the energy fluence, and consequently the dose distribution, in the object. Using three previously described bowtie filter designs, the goal of this work is to demonstrate the effect that different materials have on the bowtie filter performance measures. Methods: Three bowtie filter designs that compensate for one or more aspects of the beam-modifying effects due to the differences in path length in a projection have been designed. The nature of the designs allows for their realization using a variety of materials. The designs were based on a phantom, 14 cm in diameter, composed of 40% fibroglandular and 60% adipose tissue. Bowtie design #1 is based on single material spectral matching and produces nearly uniform spectral shape for radiation incident upon the detector. Bowtie design #2 uses the idea of basis-material decomposition to produce the same spectral shape and intensity at the detector, using two different materials. With bowtie design #3, it is possible to eliminate the beam hardening effect in the reconstructed image by adjusting the bowtie filter thickness so that the effective attenuation coefficient for every ray is the same. Seven different materials were chosen to represent a range of chemical compositions and densities. After calculation of construction parameters for each bowtie filter design, a bowtie filter was created using each of these materials (assuming reasonable construction parameters were obtained), resulting in a total of 26 bowtie filters modeled analytically and in the penelope Monte Carlo simulation environment. Using the analytical model of each bowtie filter, design profiles were obtained and energy fluence as a function of fan-angle was calculated. Projection images with and without each bowtie filter design were also generated using penelope and reconstructed using FBP. Parameters such as dose distribution, noise uniformity, and scatter were investigated. Results: Analytical calculations with and without each bowtie filter show that some materials for a given design produce bowtie filters that are too large for implementation in breast CT scanners or too small to accurately manufacture. Results also demonstrate the ability to manipulate the energy fluence distribution (dynamic range) by using different materials, or different combinations of materials, for a given bowtie filter design. This feature is especially advantageous when using photon counting detector technology. Monte Carlo simulation results from penelope show that all studied material choices for bowtie design #2 achieve nearly uniform dose distribution, noise uniformity index less than 5%, and nearly uniform scatter-to-primary ratio. These same features can also be obtained using certain materials with bowtie designs #1 and #3. Conclusions: With the three bowtie filter designs used in this work, the selection of material is an important design consideration. An appropriate material choice can improve image quality, dose uniformity, and dynamic range.

Background: Malignant pleural mesothelioma (MPM) is a rare and essentially incurable malignancy most often linked with occupational exposure to asbestos fibres. In common with other malignancies, the development and progression of MPM is associated with extensive dysregulation of cell cycle checkpoint proteins that modulate cell proliferation, apoptosis, DNA repair and senescence. Methods: The expression of cyclin-dependent kinase inhibitor p16/INK4A was evaluated by immunohistochemistry using tumour biopsy specimens from 88 MPM cases and a semi-quantitative score for p16/INK4A expression was obtained. Post-diagnosis survival and the survival benefit of chemotherapeutic intervention was correlated with p16/INK4A expression. Results: A low, intermediate and high score for p16/INK4A expression was observed for 45 (51.1%), 28 (31.8%) and 15 (17.1%) of the MPM cases, respectively. Those cases with intermediate or high p16/INK4A tumour expression had a significantly better post-diagnosis survival than those cases whose tumours lost p16 expression (log-rank P

Context.— Recurrent epidermal growth factor receptor (EGFR) mutations are seen in a subset of pulmonary adenocarcinomas. These mutations are targeted by EGFR inhibitors and are a biomarker for response to EGFR inhibitor therapies. Initial data have indicated an increased frequency of activating EGFR mutations in nonsmoking Asian females. However, there are very few studies of global scope that address the question of mutation distribution across the population of lung cancer. Objective.— To determine the frequency of EGFR mutations in exons 18 through 21 detected in clinical laboratories participating in the College of American Pathologists proficiency testing program for EGFR in calendar year 2013. Design.— We reviewed the surveys from 170 clinical laboratories from 20 countries that participated in the College of American Pathologists EGFR proficiency testing program. The proficiency testing includes questions regarding the total numbers of tests performed at each common mutation site, including both activating and resistance mutations, and their frequency. Countries were grouped into regional groups in order to assess frequency of mutation by type, and to indirectly assess ethnic differences in mutation frequencies. Results.— Among the treatment-sensitive activating mutations, the most common are exon 19 mutations (n = 10 802 of 136 533 cases; 7.9% of total cases tested) and the exon 21 L858R mutation (n = 10 351 of 136 533 cases; 7.6% of total cases tested) and the least common are exon 20 mutations (n = 466 of 136 533 cases; 0.3% of total cases tested). The T790M mutation in exon 20 is the more common resistance mutation (n = 1010 of 136 533 cases; 0.7% of all cases tested). The highest activating mutation frequency is seen in southern Asia (n = 4260 of 9337 cases; 46%) and the lowest activating mutation frequencies are in South and North America (n = 113 of 1439 cases and 7926 of 86 654 cases; 8% and 9%, respectively). Conclusions.— Our data confirm that activating EGFR mutations are more common in southern Asia and that the distribution of activating EGFR mutations varies significantly across the regions. Similarly, the frequency and distribution of resistance mutations also show significant variation when comparing southern Asia with other regions.