Determining the source and eruption dynamics of a stealth CME using NLFFF modelling and MHD simulations

Funding: S.L.Y. would like to acknowledge STFC for support via the consolidated grant SMC1/YST037 and alsoNERC for funding via the SWIMMR Aviation Risk Modelling (SWARM) Project, grant number NE/V002899/1. P.P.would like to thank the ERC for support via grant No. 647214. D.H.M. would like to thank the STFC for support via consolidated grant ST/N000609/1 and, the Leverhulme trust, and the ERC under the Synergy Grant: The Whole Sun (grant agreement no. 810218) for financial support. P.P. and D.H.M. would like to thank STFC for IAA funding under grant number SMC1-XAS012. L.A.U. was supported by the NSF Atmospheric and Geospace Sciences Postdoctoral Research Fellowship Program (Award AGS-1624438).Context. Coronal mass ejections (CMEs) that exhibit weak or no eruption signatures in the low corona, known as stealth CMEs, are problematic as upon arrival at Earth they can lead to geomagnetic disturbances that were not predicted by space weather forecasters. Aims. We investigate the origin and eruption of a stealth event that occurred on 2015 January 3 that was responsible for a strong geomagnetic storm upon its arrival at Earth. Methods. To simulate the coronal magnetic field and plasma parameters of the eruption we use a coupled approach. This approach combines an evolutionary nonlinear force-free field model of the global corona with a MHD simulation. Results. The combined simulation approach accurately reproduces the stealth event and suggests that sympathetic eruptions occur. In the combined simulation we found that three flux ropes form and then erupt. The first two flux ropes, which are connected to a large AR complex behind the east limb, erupt first producing two near-simultaneous CMEs. These CMEs are closely followed by a third, weaker flux rope eruption in the simulation that originated between the periphery of AR 12252 and the southern polar coronal hole. The third eruption coincides with a faint coronal dimming, which appears in the SDO/AIA 211 Å observations, that is attributed as the source responsible for the stealth event and later the geomagnetic disturbance at 1 AU. The incorrect interpretation of the stealth event being linked to the occurrence of a single partial halo CME observed by LASCO/C2 is mainly due to the lack of STEREO observations being available at the time of the CMEs. The simulation also shows that the LASCO CME is not a single event but rather two near-simultaneous CMEs. Conclusions. These results show the significance of the coupled data-driven simulation approach in interpreting the eruption and that an operational L5 mission is crucial for space weather forecastingPostprintPeer reviewe

Lack of Suppressive CD4+CD25+FOXP3+ T Cells in Advanced Stages of Primary Cutaneous T-Cell Lymphoma

Mycosis fungoides and its leukemic variant, Sezary syndrome, are the most common primary cutaneous T-cell lymphomas (CTCLs). In an ex vivo study, we investigated the percentage, phenotype, and suppressive function of CD4+CD25+ regulatory T cells (Tregs) from peripheral blood of CTCL patients. The percentage of Tregs did not differ significantly between patients and controls. Functional assays demonstrated a dichotomy in Treg function: in four out of 10 patients CD4+CD25+ T cells were incapable of suppressing autologous CD4+CD25− T-cell proliferation, whereas suppressive function was intact in the other six patients. Suppressive activity of Tregs inversely correlated with the peripheral blood tumor burden. T-plastin gene expression, used as a Sezary cell marker, confirmed that Sezary cells were heterogeneous for CD25 expression. Mixed lymphocyte reactions demonstrated that CD4+CD25− T cells from patients who lacked functional Tregs were susceptible to suppression by Tregs from healthy controls, and had not become suppressive themselves. Furthermore, we found reduced expression of Foxp3 in the CD4+CD25+ Tregs of these patients relative to the other six CTCL patients and controls. Our findings thus indicate a dysfunction of peripheral Tregs in certain CTCL patients, which correlates with tumor burden

A smartphone-based test for the assessment of attention deficits in delirium: A case-control diagnostic test accuracy study in older hospitalised patients.

BACKGROUND: Delirium is a common and serious acute neuropsychiatric syndrome which is often missed in routine clinical care. Inattention is the core cognitive feature. Diagnostic test accuracy (including cut-points) of a smartphone Delirium App (DelApp) for assessing attention deficits was assessed in older hospital inpatients. METHODS: This was a case-control study of hospitalised patients aged ≥65 years with delirium (with or without pre-existing cognitive impairment), who were compared to patients with dementia without delirium, and patients without cognitive impairment. Reference standard delirium assessment, which included a neuropsychological test battery, was based on Diagnostic and Statistical Manual of Mental Disorders-5 criteria. A separate blinded assessor administered the DelApp arousal assessment (score 0-4) and attention task (0-6) yielding an overall score of 0 to 10 (lower scores indicate poorer performance). Analyses included receiver operating characteristic curves and sensitivity and specificity. Optimal cut-points for delirium detection were determined using Youden's index. RESULTS: A total of 187 patients were recruited, mean age 83.8 (range 67-98) years, 152 (81%) women; n = 61 with delirium; n = 61 with dementia without delirium; and n = 65 without cognitive impairment. Patients with delirium performed poorly on the DelApp (median score = 4/10; inter-quartile range 3.0, 5.5) compared to patients with dementia (9.0; 5.5, 10.0) and those without cognitive impairment (10.0; 10.0, 10.0). Area under the curve for detecting delirium was 0.89 (95% Confidence Interval 0.84, 0.94). At an optimal cut-point of ≤8, sensitivity was 91.7% (84.7%, 98.7%) and specificity 74.2% (66.5%, 81.9%) for discriminating delirium from the other groups. Specificity was 68.3% (56.6%, 80.1%) for discriminating delirium from dementia (cut-point ≤6). CONCLUSION: Patients with delirium (with or without pre-existing cognitive impairment) perform poorly on the DelApp compared to patients with dementia and those without cognitive impairment. A cut-point of ≤8/10 is suggested as having optimal sensitivity and specificity. The DelApp is a promising tool for assessment of attention deficits associated with delirium in older hospitalised adults, many of whom have prior cognitive impairment, and should be further validated in representative patient cohorts

Effectiveness of epidural analgesia following open liver resection

AbstractObjectivesEpidural analgesia is often considered the reference standard for pain relief following major abdominal surgery; however, the provision of analgesia in the context of liver surgery raises unique challenges. This study investigated the effectiveness of analgesia and the postoperative course of patients who did or did not receive epidural analgesia following liver resection.MethodsData were collected retrospectively on 177 patients who underwent open liver resection between June 2007 and June 2009. Patients were divided into two groups consisting, respectively, of those who received epidural analgesia (Epidural group, n= 148) and those who did not (No-Epidural group, n= 29).ResultsIn the Epidural group, 27 patients (18%) required i.v. opiate analgesia on the day of surgery (DoS) or the first postoperative day (POD1). The Epidural group received significantly more i.v. colloid solution on the DoS (median: 1500ml vs. 750ml, range: 0–12000ml vs. 0–3500ml; P= 0.004) and POD1 (median: 0ml vs. 0ml, range: 0–5000ml vs. 0–1000ml; P= 0.018), and total fluid on the DoS and POD1 combined (median: 6522ml vs. 5453ml, range: 2150–21300ml vs. 2875–15886ml; P= 0.032).ConclusionsEpidural analgesia provided inadequate postoperative pain relief in approximately 20% of liver resection patients and was associated with the administration of significantly greater volumes of i.v. colloid solution

Single nucleotide polymorphisms unravel hierarchical divergence and signatures of selection among Alaskan sockeye salmon (Oncorhynchus nerka) populations

<p>Abstract</p> <p>Background</p> <p>Disentangling the roles of geography and ecology driving population divergence and distinguishing adaptive from neutral evolution at the molecular level have been common goals among evolutionary and conservation biologists. Using single nucleotide polymorphism (SNP) multilocus genotypes for 31 sockeye salmon (<it>Oncorhynchus nerka</it>) populations from the Kvichak River, Alaska, we assessed the relative roles of geography (discrete boundaries or continuous distance) and ecology (spawning habitat and timing) driving genetic divergence in this species at varying spatial scales within the drainage. We also evaluated two outlier detection methods to characterize candidate SNPs responding to environmental selection, emphasizing which mechanism(s) may maintain the genetic variation of outlier loci.</p> <p>Results</p> <p>For the entire drainage, Mantel tests suggested a greater role of geographic distance on population divergence than differences in spawn timing when each variable was correlated with pairwise genetic distances. Clustering and hierarchical analyses of molecular variance indicated that the largest genetic differentiation occurred between populations from distinct lakes or subdrainages. Within one population-rich lake, however, Mantel tests suggested a greater role of spawn timing than geographic distance on population divergence when each variable was correlated with pairwise genetic distances. Variable spawn timing among populations was linked to specific spawning habitats as revealed by principal coordinate analyses. We additionally identified two outlier SNPs located in the major histocompatibility complex (MHC) class II that appeared robust to violations of demographic assumptions from an initial pool of eight candidates for selection.</p> <p>Conclusions</p> <p>First, our results suggest that geography and ecology have influenced genetic divergence between Alaskan sockeye salmon populations in a hierarchical manner depending on the spatial scale. Second, we found consistent evidence for diversifying selection in two loci located in the MHC class II by means of outlier detection methods; yet, alternative scenarios for the evolution of these loci were also evaluated. Both conclusions argue that historical contingency and contemporary adaptation have likely driven differentiation between Kvichak River sockeye salmon populations, as revealed by a suite of SNPs. Our findings highlight the need for conservation of complex population structure, because it provides resilience in the face of environmental change, both natural and anthropogenic.</p

A quantitative assay to study the lipid selectivity of membrane-associated systems using solution NMR

The activity of membrane proteins and compounds that interact with the membrane is modulated by the surrounding lipid composition. However, there are no simple methods that determine the composition of these annular phospholipids in eukaryotic systems. Herein, we describe a simple methodology that enables the identification and quantification of the lipid composition around membrane-associated compounds using SMA-nanodiscs and routine $^1H-^{31}P NMR$

Atypical Development of Attentional Control Associates with Later Adaptive Functioning, Autism and ADHD Traits

Funder: H2020 European Research Council; doi: http://dx.doi.org/10.13039/100010663Funder: Research Foundation FlandersFunder: Universiteit Gent; doi: http://dx.doi.org/10.13039/501100004385Funder: Marguerite-Marie DelacroixFunder: Autistica; doi: http://dx.doi.org/10.13039/100011706Funder: Riksbankens Jubileumsfond; doi: http://dx.doi.org/10.13039/501100004472; Grant(s): NHS14-1802:1Funder: K.F. Hein FondsFunder: Scott Family Junior Research FellowshipAbstract: Autism is frequently associated with difficulties with top-down attentional control, which impact on individuals’ mental health and quality of life. The developmental processes involved in these attentional difficulties are not well understood. Using a data-driven approach, 2 samples (N = 294 and 412) of infants at elevated and typical likelihood of autism were grouped according to profiles of parent report of attention at 10, 15 and 25 months. In contrast to the normative profile of increases in attentional control scores between infancy and toddlerhood, a minority (7–9%) showed plateauing attentional control scores between 10 and 25 months. Consistent with pre-registered hypotheses, plateaued growth of attentional control was associated with elevated autism and ADHD traits, and lower adaptive functioning at age 3 years

Structural covariance of the ventral visual stream predicts posttraumatic intrusion and nightmare symptoms: a multivariate data fusion analysis

Visual components of trauma memories are often vividly re-experienced by survivors with deleterious consequences for normal function. Neuroimaging research on trauma has primarily focused on threat-processing circuitry as core to trauma-related dysfunction. Conversely, limited attention has been given to visual circuitry which may be particularly relevant to posttraumatic stress disorder (PTSD). Prior work suggests that the ventral visual stream is directly related to the cognitive and affective disturbances observed in PTSD and may be predictive of later symptom expression. The present study used multimodal magnetic resonance imaging data (n = 278) collected two weeks after trauma exposure from the AURORA study, a longitudinal, multisite investigation of adverse posttraumatic neuropsychiatric sequelae. Indices of gray and white matter were combined using data fusion to identify a structural covariance network (SCN) of the ventral visual stream 2 weeks after trauma. Participant\u27s loadings on the SCN were positively associated with both intrusion symptoms and intensity of nightmares. Further, SCN loadings moderated connectivity between a previously observed amygdala-hippocampal functional covariance network and the inferior temporal gyrus. Follow-up MRI data at 6 months showed an inverse relationship between SCN loadings and negative alterations in cognition in mood. Further, individuals who showed decreased strength of the SCN between 2 weeks and 6 months had generally higher PTSD symptom severity over time. The present findings highlight a role for structural integrity of the ventral visual stream in the development of PTSD. The ventral visual stream may be particularly important for the consolidation or retrieval of trauma memories and may contribute to efficient reactivation of visual components of the trauma memory, thereby exacerbating PTSD symptoms. Potentially chronic engagement of the network may lead to reduced structural integrity which becomes a risk factor for lasting PTSD symptoms

Diagnostic test accuracy of a novel smartphone application for the assessment of attention deficits in delirium in older hospitalised patients: a prospective cohort study protocol.

BACKGROUND: Delirium is a common and serious clinical syndrome which is often missed in routine clinical care. The core cognitive feature is inattention. We developed a novel bedside neuropsychological test for assessing inattention in delirium implemented on a smartphone platform (DelApp). We aim to evaluate the diagnostic performance of the DelApp in a representative cohort of older hospitalised patients. METHODS: This is a prospective study of older non-scheduled hospitalised patients (target n = 500, age ≥ 65), recruited from elderly care and acute orthopaedic wards. Exclusion criteria are: non-English speakers; severe vision or hearing impairment; photosensitive epilepsy. A structured reference standard delirium assessment based on DSM-5 criteria will be used, which includes a cognitive test battery administered by a trained assessor (Orientation-Memory-Concentration Test, Abbreviated Mental Test-10, Delirium Rating Severity Scale-Revised-98, digit span, months and days backwards, Vigilance A' test) and assessment of arousal (Observational Scale of Level of Arousal, Richmond Agitation Sedation Scale). Prior change in cognition will be documented using the Informant Questionnaire on Cognitive Decline in the Elderly. Patients will be categorized as delirium (with/without dementia), possible delirium, dementia, no cognitive impairment, or undetermined. A separate assessor (blinded to diagnosis and assessments) will administer the DelApp index test within 3 h of the reference standard assessment. The DelApp comprises assessment of arousal (score 0-4) and sustained attention (score 0-6), yielding a total score between 0 and 10 (higher score = better performance). Outcomes (length of stay, mortality and discharge location) will be collected at 12 weeks. We will evaluate a priori cutpoints derived from a previous case-control study. Measures of the accuracy of DelApp will include sensitivity, specificity, positive and negative predictive values, and area under the ROC curve. We plan repeat assessments on up to 4 occasions in a purposive subsample of 30 patients (15 delirium, 15 no delirium) to examine changes over time. DISCUSSION: This study evaluates the diagnostic test accuracy of a novel smartphone test for delirium in a representative cohort of older hospitalised patients, including those with dementia. DelApp has the potential to be a convenient, objective method of improving delirium assessment for older people in acute care. TRIAL REGISTRATION: Clinical trials.gov, NCT02590796 . Registered on 29 Oct 2015. Protocol version 5, dated 25 July 2016