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The number of active and non active satellites in Earth orbit has dramatically increased in recent decades, requiring the development of novel surveillance techniques to monitor and track them. In this paper, we build upon previous non-coherent passive radar space surveillance demonstrations undertaken using the Murchison Widefield Array (MWA). We develop the concept of the Dynamic Signal to Noise Ratio Spectrum (DSNRS) in order to isolate signals of interest (reflections of FM transmissions of objects in orbit) and efficiently differentiate them from direct path reception events. We detect and track Alouette-2, ALOS, UKube-1, the International Space Station, and Duchifat-1 in this manner. We also identified out-of-band transmissions from Duchifat-1 and UKube-1 using these techniques, demonstrating the MWA’s capability to look for spurious transmissions from satellites. We identify an offset from the locations predicted by the cataloged orbital parameters for some of the satellites, demonstrating the potential of using MWA for satellite catalog maintenance. These results demonstrate the capability of the MWA for Space Situational Awareness and we describe future work in this area.
Postpartum psychosis (PP) is a severe postpartum disorder. While working memory and emotional processing-related brain function are consistently impaired in psychoses unrelated to the puerperium, no studies have investigated them in PP.
Twenty-four women at risk of developing PP (11 developed an episode – PE; 13 remained well – NPE) and 20 healthy postpartum women completed two functional magnetic resonance imaging tasks within a year of delivery: working memory (n-back) and emotional face recognition (fearful faces). We compared women at-risk of PP to controls, as well as NPE, PE, and controls to test for potential effects of a PP episode occurrence.
Women at-risk of PP and PE showed hyperactivation of lateral visual areas, precuneus, and posterior cingulate during the n-back task. The at-risk group as a whole, as well as the PE and NPE groups, showed hyperconnectivity of the right dorsolateral prefrontal cortex (DLPFC) with various parieto-occipito-temporo-cerebellar regions compared to controls during several n-back conditions. Increases in connectivity between the right DLPFC and ipsilateral middle temporal gyrus were observed in the PE group compared to NPE during 2-back. During the fearful faces task, at-risk women as a group showed hyperactivation of fronto-cingulo-subcortical regions, and hypoconnectivity between the left amygdala and ipsilateral occipito-parietal regions compared to controls. No significant performance differences were observed.
These results present preliminary evidence of a differential nature of functional brain abnormalities in PP compared to the typically observed reduced connectivity with the DLPFC in psychoses unrelated to puerperium, such as bipolar disorder.
Scholars engaged in debates about the use of public reason often view religious arguments as being out of bounds. Yet the real-world impact of religious discourse remains under-explored. This study contributes to research in this area with an empirical test looking at the impact of religious arguments on a particular policy debate. A survey experiment explored the effects of religious and secular cues with varied policy directions on the issue of assisted dying. The findings showed that secular arguments were considerably more likely to elicit a positive response, and that, while religious arguments were not a conversation stopper, they produced significant distortions in political perceptions among participants, though not necessarily along the identity lines critical to the public reason debate.
Dissemination and implementation (D&I) science is not a formal element of the Clinical Translational Science Award (CTSA) Program, and D&I science activities across the CTSA Consortium are largely unknown.
The CTSA Dissemination, Implementation, and Knowledge Translation Working Group surveyed CTSA leaders to explore D&I science-related activities, barriers, and needed supports, then conducted univariate and qualitative analyses of the data.
Out of 67 CTSA leaders, 55.2% responded. CTSAs reported directly funding D&I programs (54.1%), training (51.4%), and projects (59.5%). Indirect support (e.g., promoted by CTSA without direct funding) for D&I activities was higher – programs (70.3%), training (64.9%), and projects (54.1%). Top barriers included funding (39.4%), limited D&I science faculty (30.3%), and lack of D&I science understanding (27.3%). Respondents (63.4%) noted the importance of D&I training and recommended coordination of D&I activities across CTSAs hubs (33.3%).
These findings should guide CTSA leadership in efforts to raise awareness and advance the role of D&I science in improving population health.
Childhood abuse is a risk factor for poorer illness course in bipolar disorder, but the reasons why are unclear. Trait-like features such as affective instability and impulsivity could be part of the explanation. We aimed to examine whether childhood abuse was associated with clinical features of bipolar disorder, and whether associations were mediated by affective instability or impulsivity.
We analysed data from 923 people with bipolar I disorder recruited by the Bipolar Disorder Research Network. Adjusted associations between childhood abuse, affective instability and impulsivity and eight clinical variables were analysed. A path analysis examined the direct and indirect links between childhood abuse and clinical features with affective instability and impulsivity as mediators.
Affective instability significantly mediated the association between childhood abuse and earlier age of onset [effect estimate (θ)/standard error (SE): 2.49], number of depressive (θ/SE: 2.08) and manic episodes/illness year (θ/SE: 1.32), anxiety disorders (θ/SE: 1.98) and rapid cycling (θ/SE: 2.25). Impulsivity significantly mediated the association between childhood abuse and manic episodes/illness year (θ/SE: 1.79), anxiety disorders (θ/SE: 1.59), rapid cycling (θ/SE: 1.809), suicidal behaviour (θ/SE: 2.12) and substance misuse (θ/SE: 3.09). Measures of path analysis fit indicated an excellent fit to the data.
Affective instability and impulsivity are likely part of the mechanism of why childhood abuse increases risk of poorer clinical course in bipolar disorder, with each showing some selectivity in pathways. They are potential novel targets for intervention to improve outcome in bipolar disorder.
The efficient and effective movement of research into practice is acknowledged as crucial to improving population health and assuring return on investment in healthcare research. The National Center for Advancing Translational Science which sponsors Clinical and Translational Science Awards (CTSA) recognizes that dissemination and implementation (D&I) sciences have matured over the last 15 years and are central to its goals to shift academic health institutions to better align with this reality. In 2016, the CTSA Collaboration and Engagement Domain Task Force chartered a D&I Science Workgroup to explore the role of D&I sciences across the translational research spectrum. This special communication discusses the conceptual distinctions and purposes of dissemination, implementation, and translational sciences. We propose an integrated framework and provide real-world examples for articulating the role of D&I sciences within and across all of the translational research spectrum. The framework’s major proposition is that it situates D&I sciences as targeted “sub-sciences” of translational science to be used by CTSAs, and others, to identify and investigate coherent strategies for more routinely and proactively accelerating research translation. The framework highlights the importance of D&I thought leaders in extending D&I principles to all research stages.
The topology and unsteady behaviour of ventilated and natural cavity flows over a two-dimensional (2-D) wall-mounted fence are investigated for fixed length cavities with varying free-stream velocity using high-speed and still imaging, X-ray densitometry and dynamic surface pressure measurement in two experimental facilities. Cavities in both ventilated and natural flows were found to have a re-entrant jet closure, but not to exhibit large-scale oscillations, yet the irregular small-scale shedding at the cavity closure. Small-scale cavity break-up was associated with a high-frequency broadband peak in the wall pressure spectra, found to be governed by the overlying turbulent boundary layer characteristics, similar to observations from single-phase flow over a forward-facing step. A low-frequency peak reflecting the oscillations in size of the re-entrant jet region, analogous to ‘flapping’ motion in single-phase flow, was found to be modulated by gravity effects (i.e. a Froude number dependence). Likewise, a significant change in cavity behaviour was observed as the flow underwent transition analogous to the transition from sub- to super-critical regime in open-channel flow. Differences in wake topology were examined using shadowgraphy and proper orthogonal decomposition, from which it was found that the size and number of shed structures increased with an increase in free-stream velocity for the ventilated case, while remaining nominally constant in naturally cavitating flow due to condensation of vaporous structures.
Increasing the number of quantum bits while preserving precise control of their quantum electronic properties is a significant challenge in materials design for the development of semiconductor quantum computing devices. Semiconductor heterostructures can host multiple quantum dots that are electrostatically defined by voltages applied to an array of metallic nanoelectrodes. The structural distortion of multiple-quantum-dot devices due to elastic stress associated with the electrodes has been difficult to predict because of the large micrometer-scale overall sizes of the devices, the complex spatial arrangement of the electrodes, and the sensitive dependence of the magnitude and spatial variation of the stress on processing conditions. Synchrotron X-ray nanobeam Bragg diffraction studies of a GaAs/AlGaAs heterostructure reveal the magnitude and nanoscale variation of these distortions. Investigations of individual linear electrodes reveal lattice tilts consistent with a 28-MPa compressive residual stress in the electrodes. The angular magnitude of the tilts varies by up to 20% over distances of less than 200 nm along the length of the electrodes, consistent with heterogeneity in the metal residual stress. A similar variation of the crystal tilt is observed in multiple-quantum-dot devices, due to a combination of the variation of the stress and the complex electrode arrangement. The heterogeneity in particular can lead to significant challenges in the scaling of multiple-quantum-dot devices due to differences between the charging energies of dots and uncertainty in the potential energy landscape. Alternatively, if incorporated in design, stress presents a new degree of freedom in device fabrication.
Viscoelastic flow past a cylinder is a classic benchmark problem that is not completely understood. Using novel three-dimensional (3D) holographic particle velocimetry, we report three main discoveries of the elastic instability upstream of a single cylinder in viscoelastic channel flow. First, we observe that upstream vortices initiate at the corner between the cylinder and the wall, and grow with increasing flow rate. Second, beyond a critical Weissenberg number, the flow upstream becomes unsteady and switches between two bistable configurations, leading to symmetry breaking in the cylinder axis direction that is highly 3D in nature. Lastly, we find that the disturbance of the elastic instability propagates relatively far upstream via an elastic wave, and is weakly correlated with that in the cylinder wake. The wave speed and the extent of the instability increase with Weissenberg number, indicating an absolute instability in viscoelastic fluids.
Schizophrenia affects 1% of the population. Clozapine is the only medication licensed for treatment-resistant schizophrenia and is intensively monitored to prevent harm from neutropenia. Clozapine is also associated with increased risk of pneumonia although the mechanism is poorly understood.
To investigate the potential association between clozapine and antibody deficiency.
Patients taking clozapine and patients who were clozapine-naive and receiving alternative antipsychotics were recruited and completed a lifestyle, medication and infection-burden questionnaire. Serum total immunoglobulins (immunoglobulin (Ig)G, IgA, IgM) and specific IgG antibodies to haemophilus influenzae type B, tetanus and IgG, IgA and IgM to pneumococcus were measured.
Immunoglobulins were all significantly reduced in the clozapine-treated group (n = 123) compared with the clozapine-naive group (n = 111). Odds ratios (ORs) for a reduction in clozapine:control immunoglobulin values below the fifth percentile were IgG, OR = 6.00 (95% CI 1.31–27.44); IgA, OR = 16.75 (95% CI 2.18–128.60); and IgM, OR = 3.26 (95% CI 1.75–6.08). These findings remained significant despite exclusion of other potential causes of hypogammaglobulinaemia. In addition, duration on clozapine was associated with decline in IgG. A higher proportion of the clozapine-treated group reported taking more than five courses of antibiotics in the preceding year (5.3% (n = 5) versus 1% (n = 1).
Clozapine use was associated with significantly reduced immunoglobulin levels and an increased proportion of patients using more than five antibiotic courses in a year. Antibody testing is not included in existing clozapine monitoring programmes but may represent a mechanistic explanation and modifiable risk factor for the increased rates of pneumonia and sepsis-related mortality previously reported in this vulnerable cohort.
Declaration of interest
S.J. has received support from CSL Behring, Shire, LFB, Biotest, Binding Site, Sanofi, GSK, UCB Pharma, Grifols, BPL SOBI, Weatherden, Zarodex and Octapharma for projects, advisory boards, meetings, studies, speaker and clinical trials.
The deep subsurface of other planetary bodies is of special interest for robotic and human exploration. The subsurface provides access to planetary interior processes, thus yielding insights into planetary formation and evolution. On Mars, the subsurface might harbour the most habitable conditions. In the context of human exploration, the subsurface can provide refugia for habitation from extreme surface conditions. We describe the fifth Mine Analogue Research (MINAR 5) programme at 1 km depth in the Boulby Mine, UK in collaboration with Spaceward Bound NASA and the Kalam Centre, India, to test instruments and methods for the robotic and human exploration of deep environments on the Moon and Mars. The geological context in Permian evaporites provides an analogue to evaporitic materials on other planetary bodies such as Mars. A wide range of sample acquisition instruments (NASA drills, Small Planetary Impulse Tool (SPLIT) robotic hammer, universal sampling bags), analytical instruments (Raman spectroscopy, Close-Up Imager, Minion DNA sequencing technology, methane stable isotope analysis, biomolecule and metabolic life detection instruments) and environmental monitoring equipment (passive air particle sampler, particle detectors and environmental monitoring equipment) was deployed in an integrated campaign. Investigations included studying the geochemical signatures of chloride and sulphate evaporitic minerals, testing methods for life detection and planetary protection around human-tended operations, and investigations on the radiation environment of the deep subsurface. The MINAR analogue activity occurs in an active mine, showing how the development of space exploration technology can be used to contribute to addressing immediate Earth-based challenges. During the campaign, in collaboration with European Space Agency (ESA), MINAR was used for astronaut familiarization with future exploration tools and techniques. The campaign was used to develop primary and secondary school and primary to secondary transition curriculum materials on-site during the campaign which was focused on a classroom extra vehicular activity simulation.
OBJECTIVES/SPECIFIC AIMS: Clostridium difficile infection (CDI) is the most common cause of antibiotic-associated diarrhea and an increasingly common infection in children in both hospital and community settings. Between 20% and 30% of pediatric patients will have a recurrence of symptoms in the days to weeks following an initial infection. Multiple recurrences have been successfully treated with fecal microbiota transplantation (FMT), though the body of evidence in pediatric patients is limited primarily to case reports and case series. The goal of our study was to better understand practices, success, and safety of FMT in children as well as identify risk factors associated with a failed FMT in our pediatric patients. METHODS/STUDY POPULATION: This multicenter retrospective analysis included 373 patients who underwent FMT for CDI between January 1, 2006 and January 1, 2017 from 18 pediatric centers. Demographics, baseline characteristics, FMT practices, C. difficile outcomes, and post-FMT complications were collected through chart abstraction. Successful FMT was defined as no recurrence of CDI within 60 days after FMT. Of the 373 patients in the cohort, 342 had known outcome data at two months post-FMT and were included in the primary analysis evaluating risk factors for recurrence post-FMT. An additional six patients who underwent FMT for refractory CDI were excluded from the primary analysis. Unadjusted analysis was performed using Wilcoxon rank-sum test, Pearson χ2 test, or Fisher exact test where appropriate. Stepwise logistic regression was utilized to determine independent predictors of success. RESULTS/ANTICIPATED RESULTS: The median age of included patients was 10 years (IQR; 3.0, 15.0) and 50% of patients were female. The majority of the cohort was White (89.0%). Comorbidities included 120 patients with inflammatory bowel disease (IBD) and 14 patients who had undergone a solid organ or stem cell transplantation. Of the 336 patients with known outcomes at two months, 272 (81%) had a successful outcome. In the 64 (19%) patients that did have a recurrence, 35 underwent repeat FMT which was successful in 20 of the 35 (57%). The overall success rate of FMT in preventing further episodes of CDI in the cohort with known outcome data was 87%. Unadjusted predictors of a primary FMT response are summarized. Based on stepwise logistic regression modeling, the use of fresh stool, FMT delivery via colonoscopy, the lack of a feeding tube, and a lower number of CDI episodes before undergoing FMT were independently associated with a successful outcome. There were 20 adverse events in the cohort assessed to be related to FMT, 6 of which were felt to be severe. There were no deaths assessed to be related to FMT in the cohort. DISCUSSION/SIGNIFICANCE OF IMPACT: The overall success of FMT in pediatric patients with recurrent or severe CDI is 81% after a single FMT. Children without a feeding tube, who receive an early FMT, FMT with fresh stool, or FMT via colonoscopy are less likely to have a recurrence of CDI in the 2 months following FMT. This is the first large study of FMT for CDI in a pediatric cohort. These findings, if confirmed by additional prospective studies, will support alterations in the practice of FMT in children.
Species richness is not evenly distributed across the tree of life and a limited number of lineages comprise an extraordinarily large number of species. In lichen-forming fungi, only two genera are known to be ‘ultradiverse’ (>500 species), with the most diverse genus, Xanthoparmelia, consisting of c. 820 species. While Australia and South Africa are known as current centres of diversity for Xanthoparmelia, it is not well known when and where this massive diversity arose. To better understand the geographical and temporal context of diversification in this diverse genus, we sampled 191 Xanthoparmelia specimens representing c. 124 species/species-level lineages from populations worldwide. From these specimens, we generated a multi-locus sequence data set using Sanger and high-throughput sequencing to reconstruct evolutionary relationships in Xanthoparmelia, estimate divergence times and reconstruct biogeographical histories in a maximum likelihood and Bayesian framework. This study corroborated the phylogenetic placement of several morphologically or chemically diverse taxa within Xanthoparmelia, such as Almbornia, Chondropsis, Karoowia, Namakwa, Neofuscelia, Omphalodiella, Paraparmelia, Placoparmelia and Xanthomaculina, in addition to improved phylogenetic resolution and reconstruction of previously unsampled lineages within Xanthoparmelia. Our data indicate that Xanthoparmelia most likely originated in Africa during the early Miocene, coinciding with global aridification and development of open habitats. Reconstructed biogeographical histories of Xanthoparmelia reveal diversification restricted to continents with infrequent intercontinental exchange by long-distance dispersal. While likely mechanisms by which Xanthoparmelia obtained strikingly high levels of species richness in Australia and South Africa remain uncertain, this study provides a framework for ongoing research into diverse lineages of lichen-forming fungi. Finally, our study highlights a novel approach for generating locus-specific molecular sequence data sets from high throughput metagenomic reads.
Neurocognitive deficits are often seen as core features of schizophrenia, and as primary determinants of poor functioning. Yet, our clinical observations suggest that individuals who score within the impaired range on standardized tests can reliably perform better in complex real-world situations, especially when performance is embedded within a positive socio-affective context.
We analyzed literature on the influence of non-neurocognitive factors on test performance in order to clarify their contributions.
We identified seven non-neurocognitive factors that significantly contribute to neurocognitive test performance: avolition, dysfunctional attitudes, effort, stress, negative emotions, asociality, and disorganized symptoms. We then proposed an alternative model based on dysfunctional (e.g. defeatist) attitudes and their consequences for motivation and sustained task engagement. We demonstrated that these factors account for substantial variance in negative symptoms, neurocognitive test performance, and functional outcomes. We then demonstrated that recovery-oriented cognitive therapy – which is derived from this alternative model and primarily targets dysfunctional beliefs – has been successful in the treatment of low functioning individuals with schizophrenia.
The contributions of neurocognitive impairments to poor real-world functioning in people with schizophrenia may be overstated in the literature, and may even be limited relative to non-neurocognitive factors. We offer suggestions for further research to more precisely quantify the contributions of attitudinal/motivation v. neurocognitive factors in schizophrenia.
Tumor profiling tests can help to identify whether women with breast cancer need chemotherapy due to their risk of relapse, and some may be able to predict benefit from chemotherapy. We focused on four genetic tests: Oncotype DX (O-DX), MammaPrint (MMP), EndoPredict and Prosigna, and one immunohistochemistry test, IHC4, for the National Institute of Health and Care Excellence as part of their Diagnostic Appraisal Programme.
A systematic review was undertaken, including searching of nine databases in February 2017 plus other sources including a previous review published in 2013. The review included studies assessing clinical effectiveness of the five tumor profiling tests, with or without clinicopathological factors, to guide decisions about adjuvant chemotherapy in people with ER-positive, HER-2 negative, Stage I-II cancer with 0 to 3 positive lymph nodes (LN). The PROBAST tool and Cochrane risk of bias tools were used to assess risk of bias.
A total of 153 studies were included; the strength of evidence base for individual tests was varied. Results suggest all tests are prognostic for risk of relapse, though results were more varied in LN positive (+) patients than in LN negative (0) patients. Evidence was limited about whether tests can predict benefit from chemotherapy (available for MMP and O-DX only). Studies that assessed the impact of the tests on clinical decisions indicate that the net change in chemotherapy recommendations or decisions pre-/post-test ranged from an increase of one percent to a decrease of 23 percent among UK studies, and a decrease of zero percent to 64 percent across European studies.
The studies included in the review suggest that all of the tests can provide prognostic information on the risk of relapse; however results were more varied in LN+ patients than in LN0 patients. There is limited and varying evidence for prediction of chemotherapy benefit.
An internationally approved and globally used classification scheme for the diagnosis of CHD has long been sought. The International Paediatric and Congenital Cardiac Code (IPCCC), which was produced and has been maintained by the International Society for Nomenclature of Paediatric and Congenital Heart Disease (the International Nomenclature Society), is used widely, but has spawned many “short list” versions that differ in content depending on the user. Thus, efforts to have a uniform identification of patients with CHD using a single up-to-date and coordinated nomenclature system continue to be thwarted, even if a common nomenclature has been used as a basis for composing various “short lists”. In an attempt to solve this problem, the International Nomenclature Society has linked its efforts with those of the World Health Organization to obtain a globally accepted nomenclature tree for CHD within the 11th iteration of the International Classification of Diseases (ICD-11). The International Nomenclature Society has submitted a hierarchical nomenclature tree for CHD to the World Health Organization that is expected to serve increasingly as the “short list” for all communities interested in coding for congenital cardiology. This article reviews the history of the International Classification of Diseases and of the IPCCC, and outlines the process used in developing the ICD-11 congenital cardiac disease diagnostic list and the definitions for each term on the list. An overview of the content of the congenital heart anomaly section of the Foundation Component of ICD-11, published herein in its entirety, is also included. Future plans for the International Nomenclature Society include linking again with the World Health Organization to tackle procedural nomenclature as it relates to cardiac malformations. By doing so, the Society will continue its role in standardising nomenclature for CHD across the globe, thereby promoting research and better outcomes for fetuses, children, and adults with congenital heart anomalies.