scholarly journals Spatial distribution of interictal spikes fluctuates over time and localizes seizure onset

Brain ◽  
2019 ◽  
Vol 143 (2) ◽  
pp. 554-569 ◽  
Author(s):  
Erin C Conrad ◽  
Samuel B Tomlinson ◽  
Jeremy N Wong ◽  
Kelly F Oechsel ◽  
Russell T Shinohara ◽  
...  
Keyword(s):  
Spatial Distribution ◽  
Temporal Dynamics ◽  
Spatial Location ◽  
Rank Test ◽  
Interictal Spikes ◽  
Seizure Onset ◽  
Fisher's Method ◽  
Aggregate Effect ◽  
Fisher’S Method ◽  
Over Time

Abstract The location of interictal spikes is used to aid surgical planning in patients with medically refractory epilepsy; however, their spatial and temporal dynamics are poorly understood. In this study, we analysed the spatial distribution of interictal spikes over time in 20 adult and paediatric patients (12 females, mean age = 34.5 years, range = 5–58) who underwent intracranial EEG evaluation for epilepsy surgery. Interictal spikes were detected in the 24 h surrounding each seizure and spikes were clustered based on spatial location. The temporal dynamics of spike spatial distribution were calculated for each patient and the effects of sleep and seizures on these dynamics were evaluated. Finally, spike location was assessed in relation to seizure onset location. We found that spike spatial distribution fluctuated significantly over time in 14/20 patients (with a significant aggregate effect across patients, Fisher’s method: P < 0.001). A median of 12 sequential hours were required to capture 80% of the variability in spike spatial distribution. Sleep and postictal state affected the spike spatial distribution in 8/20 and 4/20 patients, respectively, with a significant aggregate effect (Fisher’s method: P < 0.001 for each). There was no evidence of pre-ictal change in the spike spatial distribution for any patient or in aggregate (Fisher’s method: P = 0.99). The electrode with the highest spike frequency and the electrode with the largest area of downstream spike propagation both localized the seizure onset zone better than predicted by chance (Wilcoxon signed-rank test: P = 0.005 and P = 0.002, respectively). In conclusion, spikes localize seizure onset. However, temporal fluctuations in spike spatial distribution, particularly in relation to sleep and post-ictal state, can confound localization. An adequate duration of intracranial recording—ideally at least 12 sequential hours—capturing both sleep and wakefulness should be obtained to sufficiently sample the interictal network.

scholarly journals Spatial-Temporal Variation in the Impacts of Urban Infrastructure on Housing Prices in Wuhan, China

2020 ◽  
Vol 12 (3) ◽  
pp. 1281 ◽  
Author(s):  
Fan Liu ◽  
Min Min ◽  
Ke Zhao ◽  
Weiyan Hu
Keyword(s):  
Spatial Distribution ◽  
Urban Area ◽  
Temporal Dynamics ◽  
Housing Prices ◽  
Influence Factors ◽  
Urban Infrastructure ◽  
Spatial Location ◽  
Influential Factors ◽  
Rapid Urbanization ◽  
The Impact

This study aims to investigate the spatial and temporal dynamics of housing prices associated with the urban infrastructure in Wuhan, China. The relationship between urban infrastructure and housing prices during rapid urbanization has drawn popular concerns. This article takes 619 residential communities during the period 2010 to 2018 in Wuhan’s main urban area as research units, and uses the geographically and temporally weighted regression (GTWR) model to study the spatial-temporal differentiation in the effects of urban infrastructure on housing prices. The results show that: 1) From 2010 to 2018, housing prices in Wuhan’s main urban area were generally on the rise, but the increment speed has shown an obvious periodic characteristic, the spatial distribution of housing prices has shown an obvious core and periphery distribution and the peak value area shifted from Hankou to Wuchang. 2) The influential factors of housing prices have significant spatiotemporal non-stationarity, while the impact, direction and intensity of the influential factors varies in time and space. Spatially, the influence factors show different differentiation rules for spatial distribution, and the influencing direction and strength of the urban infrastructure on housing prices are closely related to the spatial location, distribution density and the type of urban infrastructure. Temporally, the influencing strength of various urban facilities varies. This research will benefit both urban planners for optimizing urban facilities and policy-makers for formulating more specific housing policies, which ultimately contributes to urban sustainability.

SPATIAL DISTRIBUTION AND MORPHOMETRIC ANALYSIS OF DOLINES OVER TIME IN A WASTEWATER SPRAY IRRIGATED LANDSCAPE

2017 ◽  
Author(s):  
Timothy J. Daniel ◽  
◽  
John Richendrfer ◽  
Henry Lin ◽  
Heather Gall ◽  
...  
Keyword(s):  
Spatial Distribution ◽  
Morphometric Analysis ◽  
Over Time

scholarly journals 49 In situ phenotypic analysis of T cells in the tumor microenvironment of a pre-clinical model of non-small cell lung cancer (NSCLC) by tissue sectioning and whole-mount immunofluorescence imaging

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A52-A52
Author(s):  
Elen Torres ◽  
Stefani Spranger
Keyword(s):  
T Cells ◽  
Spatial Distribution ◽  
T Cell ◽  
Spatial Location ◽  
Cell Infiltration ◽  
Cell Populations ◽  
Tumor Bearing ◽  
T Cell Infiltration ◽  
Volume Imaging ◽  
Whole Mount

BackgroundUnderstanding the interactions between tumor and immune cells is critical for improving current immunotherapies. Pre-clinical and clinical evidence has shown that failed T cell infiltration into lung cancer lesions might be associated with low responsiveness towards checkpoint blockade.1 For this reason, it is necessary to characterize not only the phenotype of T cells in tumor-bearing lungs but also their spatial location in the tumor microenvironment (TME). Multiplex immunofluorescence staining allows the simultaneous use of several cell markers to study the state and the spatial location of cell populations in the tissue of interest. Although this technique is usually applied to thin tissue sections (5 to 12 µm), the analysis of large tissue volumes may provide a better understanding of the spatial distribution of cells in relation to the TME. Here, we analyzed the number and spatial distribution of cytotoxic T cells and other immune cells in the TME of tumor-bearing lungs, using both 12 µm sections and whole-mount preparations imaged by confocal microscopy.MethodsLung tumors were induced in C57BL/6 mice by tail vein injection of a cancer cell line derived from KrasG12D/+ and Tp53-/- mice. Lung tissue with a diverse degree of T cell infiltration was collected after 21 days post tumor induction. Tissue was fixed in 4% PFA, followed by snap-frozen for sectioning. Whole-mount preparations were processed according to Weizhe Li et al. (2019) 2 for tissue clearing and multiplex volume imaging. T cells were labeled with CD8 and FOXP3 antibodies to identify cytotoxic or regulatory T cells, respectively. Tumor cells were labeled with a pan-Keratin antibody. Images were acquired using a Leica SP8 confocal microscope. FIJI3 and IMARIS were used for image processing.ResultsWe identified both cytotoxic and regulatory T cell populations in the TME using thin sections and whole-mount. However, using whole-mount after tissue clearing allowed us to better evaluate the spatial distribution of the T cell populations in relation to the tumor structure. Furthermore, tissue clearance facilitates the imaging of larger volumes using multiplex immunofluorescence.ConclusionsAnalysis of large lung tissue volumes provides a better understanding of the location of immune cell populations in relation to the TME and allows to study heterogeneous immune infiltration on a per-lesion base. This valuable information will improve the characterization of the TME and the definition of cancer-immune phenotypes in NSCLC.ReferencesTeng MW, et al., Classifying cancers based on T-cell infiltration and PD-L1. Cancer Res 2015;75(11): p. 2139–45.Li W, Germain RN, and Gerner MY. High-dimensional cell-level analysis of tissues with Ce3D multiplex volume imaging. Nat Protoc 2019;14(6): p. 1708–1733.Schindelin J, et al, Fiji: an open-source platform for biological-image analysis. Nat Methods 2012;9(7): p. 676–82.

scholarly journals Acute symptoms of mild to moderate COVID-19 are highly heterogeneous across individuals and over time

2021 ◽  
Author(s):  
Thomas L Rodebaugh ◽  
Madelyn R Frumkin ◽  
Angela M Reiersen ◽  
Eric J Lenze ◽  
Michael S Avidan ◽  
...  
Keyword(s):  
Temporal Dynamics ◽  
Survey Methods ◽  
Clinical Care ◽  
Clinical Deterioration ◽  
Symptom Profiles ◽  
Fluctuating Course ◽  
The Common ◽  
Symptom Changes ◽  
Over Time

Abstract Background The symptoms of COVID-19 appear to be heterogenous, and the typical course of these symptoms is unknown. Our objectives were to characterize the common trajectories of COVID-19 symptoms and assess how symptom course predicts other symptom changes as well as clinical deterioration. Methods 162 participants with acute COVID-19 responded to surveys up to 31 times for up to 17 days. Several statistical methods were used to characterize the temporal dynamics of these symptoms. Because nine participants showed clinical deterioration, we explored whether these participants showed any differences in symptom profiles. Results Trajectories varied greatly between individuals, with many having persistently severe symptoms or developing new symptoms several days after being diagnosed. A typical trajectory was for a symptom to improve at a decremental rate, with most symptoms still persisting to some degree at the end of the reporting period. The pattern of symptoms over time suggested a fluctuating course for many patients. Participants who showed clinical deterioration were more likely to present with higher reports of severity of cough and diarrhea. Conclusion The course of symptoms during the initial weeks of COVID-19 is highly heterogeneous and is neither predictable nor easily characterized using typical survey methods. This has implications for clinical care and early-treatment clinical trials. Additional research is needed to determine whether the decelerating improvement pattern seen in our data is related to the phenomenon of patients reporting long-term symptoms, and whether higher symptoms of diarrhea in early illness presages deterioration.

scholarly journals POS0619 MODELLING OF DISEASE ACTIVITY IN PATIENTS WITH INFLAMMATORY ARTHROPATHIES TREATED WITH ETANERCEPT ORIGINATOR OR BIOSIMILAR AS FIRST-LINE BIOLOGIC IN AN AUSTRALIAN REAL-WORLD DATASET

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 547.1-547
Author(s):  
C. Deakin ◽  
G. Littlejohn ◽  
H. Griffiths ◽  
T. Smith ◽  
C. Osullivan ◽  
...  
Keyword(s):  
Disease Activity ◽  
Clinical Data ◽  
Real World ◽  
Rank Test ◽  
P Value ◽  
Continuous Variables ◽  
Linear Quadratic ◽  
First Line ◽  
Modest Improvement ◽  
Over Time

Background:The availability of biosimilars as non-proprietary versions of established biologic disease-modifying anti-rheumatic drugs (bDMARDs) is enabling greater access for patients with rheumatic diseases to effective medications at a lower cost. Since April 2017 both the originator and a biosimilar for etanercept (trade names Enbrel and Brenzys, respectively) have been available for use in Australia.Objectives:[1]To model effectiveness of etanercept originator or biosimilar in reducing Disease Activity Score 28-joint count C reactive protein (DAS28CRP) in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) or ankylosing spondylitis (AS) treated with either drug as first-line bDMARD[2]To describe persistence on etanercept originator or biosimilar as first-line bDMARD in patients with RA, PsA or ASMethods:Clinical data were obtained from the Optimising Patient outcomes in Australian rheumatoLogy (OPAL) dataset, derived from electronic medical records. Eligible patients with RA, PsA or AS who initiated etanercept originator (n=856) or biosimilar (n=477) as first-line bDMARD between 1 April 2017 and 31 December 2020 were identified. Propensity score matching was performed to select patients on originator (n=230) or biosimilar (n=136) with similar characteristics in terms of diagnosis, disease duration, joint count, age, sex and concomitant medications. Data on clinical outcomes were recorded at 3 months after baseline, and then at 6-monthly intervals. Outcomes data that were missing at a recorded visit were imputed.Effectiveness of the originator, relative to the biosimilar, for reducing DAS28CRP over time was modelled in the matched population using linear mixed models with both random intercepts and slopes to allow for individual heterogeneity, and weighting of individuals by inverse probability of treatment weights to ensure comparability between treatment groups. Time was modelled as a combination of linear, quadratic and cubic continuous variables.Persistence on the originator or biosimilar was analysed using survival analysis (log-rank test).Results:Reduction in DAS28CRP was associated with both time and etanercept originator treatment (Table 1). The conditional R-squared for the model was 0.31. The average predicted DAS28CRP at baseline, 3 months, 6 months, 9 months and 12 months were 4.0 and 4.4, 3.1 and 3.4, 2.6 and 2.8, 2.3 and 2.6, and 2.2 and 2.4 for the originator and biosimilar, respectively, indicating a clinically meaningful effect of time for patients on either drug and an additional modest improvement for patients on the originator.Median time to 50% of patients stopping treatment was 25.5 months for the originator and 24.1 months for the biosimilar (p=0.53). An adverse event was the reason for discontinuing treatment in 33 patients (14.5%) on the originator and 18 patients (12.9%) on the biosimilar.Conclusion:Analysis using a large national real-world dataset showed treatment with either the etanercept originator or the biosimilar was associated with a reduction in DAS28CRP over time, with the originator being associated with a further modest reduction in DAS28CRP that was not clinically significant. Persistence on treatment was not different between the two drugs.Table 1.Respondent characteristics.Fixed EffectEstimate95% Confidence Intervalp-valueTime (linear)0.900.89, 0.911.5e-63Time (quadratic)1.011.00, 1.011.3e-33Time (cubic)1.001.00, 1.007.1e-23Originator0.910.86, 0.960.0013Acknowledgements:The authors acknowledge the members of OPAL Rheumatology Ltd and their patients for providing clinical data for this study, and Software4Specialists Pty Ltd for providing the Audit4 platform.Supported in part by a research grant from Investigator-Initiated Studies Program of Merck & Co Inc, Kenilworth, NJ, USA. The opinions expressed in this paper are those of the authors and do not necessarily represent those of Merck & Co Inc, Kenilworth, NJ, USA.Disclosure of Interests:Claire Deakin: None declared, Geoff Littlejohn Consultant of: Over the last 5 years Geoffrey Littlejohn has received educational grants and consulting fees from AbbVie, Bristol Myers Squibb, Eli Lilly, Gilead, Novartis, Pfizer, Janssen, Sandoz, Sanofi and Seqirus., Hedley Griffiths Consultant of: AbbVie, Gilead, Novartis and Lilly., Tegan Smith: None declared, Catherine OSullivan: None declared, Paul Bird Speakers bureau: Eli Lilly, abbvie, pfizer, BMS, UCB, Gilead, Novartis

scholarly journals Longitudinal Patterns of Ethical Organisational Culture as a Context for Leaders’ Well-Being: Cumulative Effects Over 6 Years

2021 ◽  
Author(s):  
Mari Huhtala ◽  
Muel Kaptein ◽  
Joona Muotka ◽  
Taru Feldt
Keyword(s):  
Latent Profile Analysis ◽  
Temporal Dynamics ◽  
Ethical Dilemmas ◽  
Extended Period ◽  
Well Being ◽  
Organisational Culture ◽  
Cumulative Effects ◽  
Ethical Culture ◽  
Continuous Increase ◽  
Over Time

AbstractThe aim of this longitudinal study was to investigate the temporal dynamics of ethical organisational culture and how it associates with well-being at work when potential changes in ethical culture are measured over an extended period of 6 years. We used a person-centred study design, which allowed us to detect both typical and atypical patterns of ethical culture stability as well as change among a sample of leaders. Based on latent profile analysis and hierarchical linear modelling we found longitudinal, concurrent relations and cumulative gain and loss cycles between different ethical culture patterns and leaders’ well-being. Leaders in the strongest ethical culture pattern experienced the highest level of work engagement and a decreasing level of ethical dilemmas and stress. Leaders who gave the lowest ratings on ethical culture which also decreased over time reported the highest level of ethical dilemmas, stress, and burnout. They also showed a continuous increase in these negative outcomes over time. Thus, ethical culture has significant cumulative effects on well-being, and these longitudinal effects can be both negative and positive, depending on the experienced strength of the culture’s ethicality.

scholarly journals 520. Longitudinal Analysis of SARS-CoV-2 Viruses in Hospitalized Adults

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S325-S326
Author(s):  
Lacy Simons ◽  
Ramon Lorenzo-Redondo ◽  
Hannah Nam ◽  
Scott C Roberts ◽  
Michael G Ison ◽  
...  
Keyword(s):  
Viral Load ◽  
Genome Sequencing ◽  
Viral Genome ◽  
Temporal Dynamics ◽  
Population Level ◽  
Hospital Staff ◽  
Therapeutic Interventions ◽  
Viral Loads ◽  
Qrt Pcr ◽  
Over Time

Abstract Background The rapid spread of SARS-CoV-2, the causative agent of Coronavirus disease 2019 (COVID-19), has been accompanied by the emergence of viral mutations, some of which may have distinct virological and clinical consequences. While whole genome sequencing efforts have worked to map this viral diversity at the population level, little is known about how SARS-CoV-2 may diversify within a host over time. This is particularly important for understanding the emergence of viral resistance to therapeutic interventions and immune pressure. The goal of this study was to assess the change in viral load and viral genome sequence within patients over time and determine if these changes correlate with clinical and/or demographic parameters. Methods Hospitalized patients admitted to Northwestern Memorial Hospital with a positive SARS-CoV-2 test were enrolled in a longitudinal study for the serial collection of nasopharyngeal specimens. Swabs were administered to patients by hospital staff every 4 ± 1 days for up to 32 days or until the patients were discharged. RNA was extracted from each specimen and viral loads were calculated by quantitative reverse transcriptase PCR (qRT-PCR). Specimens with qRT-PCR cycle threshold values less than or equal to 30 were subject to whole viral genome sequencing by reverse transcription, multiplex PCR, and deep sequencing. Variant populations sizes were estimated and subject to phylogenetic analysis relative to publicly available SARS-CoV-2 sequences. Sequence and viral load data were subsequently correlated to available demographic and clinical data. Results 60 patients were enrolled from March 26th to June 20th, 2020. We observed an overall decrease in nasopharyngeal viral load over time across all patients. However, the temporal dynamics of viral load differed on a patient-by-patient basis. Several mutations were also observed to have emerged within patients over time. Distribution of SARS-CoV-2 viral loads in serially collected nasopharyngeal swabs in hospitalized adults as determined by qRT-PCR. Samples were collected every 4 ± 1 days (T#1–8) and viral load is displayed by log(copy number). Conclusion These data indicate that SARS-CoV-2 viral loads in the nasopharynx decrease over time and that the virus can accumulate mutations during replication within individual patients. Future studies will examine if some of these mutations may provide fitness advantages in the presence of therapeutic and/or immune selective pressures. Disclosures Michael G. Ison, MD MS, AlloVir (Consultant)

scholarly journals Spatial distribution and temporal variation of microcrustaceans assembly (Cladocera and Copepoda) in different compartments of a reservoir in the brazilian semiarid region

2018 ◽  
Vol 30 (0) ◽  
Author(s):  
Josiane Souza Santos ◽  
Nadson Ressyé Simões ◽  
Sérgio Luiz Sonoda
Keyword(s):  
Spatial Distribution ◽  
Spatial Variation ◽  
Temporal Variation ◽  
Aquatic Macrophytes ◽  
Temporal Dynamics ◽  
Lateral Compartment ◽  
Spatial And Temporal Variation ◽  
Semiarid Region ◽  
Brazilian Semiarid ◽  
Significant Spatial Variation

Abstract Aim: The objective of this study was to investigate the spatial and temporal variation of microcrustacean assemblages of a reservoir in the Brazilian semiarid region. Methods Physical and chemical water variables and samples of microcrustaceans were collected at eight sites of the reservoir between July 2013 and November 2014, in a total of seven campaigns. For this study, the reservoir was categorized in two compartments: lateral and central. Results Limnological variables showed significant temporal variation (PERMANOVA, Pseudo-F = 19.51, p = 0.001). Higher turbidity values and suspended solids were observed in the rainiest months, while during the dry months, we measured higher values of transparency, dissolved oxygen, and chlorophyll-a. It was not found significant spatial variation of limnological variables (PERMANOVA, Pseudo-F = 0.96; p = 0.394). During the study period, ten species were recorded: four Cladocera (Ceriodaphnia cornuta, Daphnia gessneri, Diaphanosoma birgei and Diaphanosoma spinulosum ) three Copepoda Calanoida (Argyrodiaptomus azevedoi, Notodiaptomus cearensis and Notodiaptomus iheringi) and three Copepoda Cyclopoida (Macrocyclops albidus, Thermocyclops minutus and Thermocyclops decipiens). The microcrustacean assemblages showed significant temporal variation (PERMANOVA, Pseudo-F = 4.34; p = 0.001) as well as significant spatial variation (PERMANOVA, Pseudo-F = 9.46; p = 0.001). The highest values of abundance and richness were observed in the lateral compartment, this result is mainly related to the presence of aquatic macrophytes in this region, because the analysis of partial RDA indicated that limnological variables explained only 11% of this variation (Pseudo-F = 2.08, p = 0.001). Conclusions The results suggest that the seasonality of the semiarid is an important factor in the temporal dynamics of the limnological variables, while the aquatic macrophytes play an important role in the spatial distribution of the microcrustacean assembly.

scholarly journals Temporal Dynamics of Cloacal Microbiota in Adult Laying Chickens With and Without Access to an Outdoor Range

2021 ◽  
Vol 11 ◽  
Author(s):  
Janneke Schreuder ◽  
Francisca C. Velkers ◽  
Alex Bossers ◽  
Ruth J. Bouwstra ◽  
Willem F. de Boer ◽  
...  
Keyword(s):  
Microbial Community ◽  
Community Composition ◽  
Intestinal Microbiota ◽  
Environmental Changes ◽  
Temporal Dynamics ◽  
Microbial Community Composition ◽  
Sudden Change ◽  
Rrna Gene ◽  
Poultry House ◽  
Over Time

Associations between animal health and performance, and the host’s microbiota have been recently established. In poultry, changes in the intestinal microbiota have been linked to housing conditions and host development, but how the intestinal microbiota respond to environmental changes under farm conditions is less well understood. To gain insight into the microbial responses following a change in the host’s immediate environment, we monitored four indoor flocks of adult laying chickens three times over 16 weeks, during which two flocks were given access to an outdoor range, and two were kept indoors. To assess changes in the chickens’ microbiota over time, we collected cloacal swabs of 10 hens per flock and performed 16S rRNA gene amplicon sequencing. The poultry house (i.e., the stable in which flocks were housed) and sampling time explained 9.2 and 4.4% of the variation in the microbial community composition of the flocks, respectively. Remarkably, access to an outdoor range had no detectable effect on microbial community composition, the variability of microbiota among chickens of the same flock, or microbiota richness, but the microbiota of outdoor flocks became more even over time. Fluctuations in the composition of the microbiota over time within each poultry house were mainly driven by turnover in rare, rather than dominant, taxa and were unique for each flock. We identified 16 amplicon sequence variants that were differentially abundant over time between indoor and outdoor housed chickens, however none were consistently higher or lower across all chickens of one housing type over time. Our study shows that cloacal microbiota community composition in adult layers is stable following a sudden change in environment, and that temporal fluctuations are unique to each flock. By exploring microbiota of adult poultry flocks within commercial settings, our study sheds light on how the chickens’ immediate environment affects the microbiota composition.

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