scholarly journals Temporal integration of inductive cues on the way to gastrulation

2021 ◽  
Vol 118 (23) ◽  
pp. e2102691118
Author(s):  
Sarah McFann ◽  
Sayantan Dutta ◽  
Jared E. Toettcher ◽  
Stanislav Y. Shvartsman
Keyword(s):  
Time Window ◽  
Temporal Integration ◽  
Critical Time ◽  
Early Embryo ◽  
Mesodermal Cell ◽  
Cell Movements ◽  
Ventral Furrow ◽  
Transcriptional Dynamics ◽  
Extracellular Signal ◽  
External Signals

Markers for the endoderm and mesoderm germ layers are commonly expressed together in the early embryo, potentially reflecting cells’ ability to explore potential fates before fully committing. It remains unclear when commitment to a single-germ layer is reached and how it is impacted by external signals. Here, we address this important question in Drosophila, a convenient model system in which mesodermal and endodermal fates are associated with distinct cellular movements during gastrulation. Systematically applying endoderm-inducing extracellular signal-regulated kinase (ERK) signals to the ventral medial embryo—which normally only receives a mesoderm-inducing cue—reveals a critical time window during which mesodermal cell movements and gene expression are suppressed by proendoderm signaling. We identify the ERK target gene huckebein (hkb) as the main cause of the ventral furrow suppression and use computational modeling to show that Hkb repression of the mesoderm-associated gene snail is sufficient to account for a broad range of transcriptional and morphogenetic effects. Our approach, pairing precise signaling perturbations with observation of transcriptional dynamics and cell movements, provides a general framework for dissecting the complexities of combinatorial tissue patterning.

scholarly journals Time-Varying Associations Between an Exposure History and a Subsequent Health Outcome: A landmark Approach to Identify Critical Windows.

2021 ◽  
Author(s):  
Maude Wagner ◽  
Francine Grodstein ◽  
Karen Leffondre ◽  
Cécilia Samieri ◽  
Cécile Proust-Lima
Keyword(s):  
Risk Factors ◽  
Health Outcome ◽  
Measurement Errors ◽  
Mixed Model ◽  
Time Window ◽  
Time Windows ◽  
Critical Time ◽  
Cumulative Exposure ◽  
Exposure Measurement ◽  
Exposure History

Abstract Background: Long-term behavioral and health risk factors constitute a primary focus of research on the etiology of chronic diseases. Yet, identifying critical time-windows during which risk factors have the strongest impact on disease risk is challenging. To assess the trajectory of association of an exposure history with an outcome, the weighted cumulative exposure index (WCIE) has been proposed, with weights reflecting the relative importance of exposures at different times. However, WCIE is restricted to a complete observed error-free exposure whereas exposures are often measured with intermittent missingness and error. Moreover, it rarely explores exposure history that is very distant from the outcome as usually sought in life-course epidemiology.Methods: We extend the WCIE methodology to (i) exposures that are intermittently measured with error, and (ii) contexts where the exposure time-window precedes the outcome time-window using a landmark approach. First, the individual exposure history up to the landmark time is estimated using a mixed model that handles missing data and error in exposure measurement, and the predicted complete error-free exposure history is derived. Then the WCIE methodology is applied to assess the trajectory of association between the predicted exposure history and the health outcome collected after the landmark time. In our context, the health outcome is a longitudinal marker analyzed using a mixed model.Results: A simulation study first demonstrates the correct inference obtained with this approach. Then, applied to the Nurses’ Health Study (19,415 women) to investigate the association between body mass index history (collected from midlife) and subsequent cognitive decline (evaluated after age 70), the method identified two major critical windows of association: long before the first cognitive evaluation (roughly 24 to 12 years), higher levels of BMI were associated with poorer cognition. In contrast, adjusted for the whole history, higher levels of BMI became associated with better cognition in the last years prior to the first cognitive interview, thus reflecting reverse causation (changes in exposure due to underlying disease).Conclusions: This approach, easy to implement, provides a flexible tool for studying complex dynamic relationships and identifying critical time windows while accounting for exposure measurement errors.

scholarly journals Clinical Evaluation of Herbal Medicine (ICH-012) in Treating Acute Cerebral Haemorrhage: Safety and Efficacy from 6- to 72-Hour Time Window (CRRICHTrial-II)

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Qixin Zhang ◽  
Liling Zeng ◽  
Xiuyan Chen ◽  
Yuexiang Zhou ◽  
Baoying Gong ◽  
...  
Keyword(s):  
Herbal Medicine ◽  
Ct Scan ◽  
Time Window ◽  
Rapid Change ◽  
Herbal Medicines ◽  
Critical Time ◽  
Cerebral Haemorrhage ◽  
High Morbidity ◽  
Safety And Efficacy ◽  
Link Type

Background. Hypertensive intracerebral haemorrhage (HICH), which is characterized by rapid change, high morbidity, and mortality, is extremely dangerous. Both medical and surgical treatments lack definitive evidence and remain controversial. A prospective RCT that we have conducted has shown that the usage of the herbal medicine ICH-012 within 6 h of the event may increase the risk of haematoma enlargement and gastrointestinal bleeding. However, the volume of haematoma remains stable after 6 h. Thus, we will increase the time window to the period from 6 to 72 h after onset to evaluate the safety and efficacy of ICH-012 treating ICH (ClinicalTrial.gov ID: NCT03354026). Methods/Design. The CRRICHTrial-II study, a prospective, double-blinded, controlled, multicentre RCT, includes three groups: A, B, and C. Group A patients were treated with 8 herbal medicines (with 2 herbal medicines of Hirudo and Tabanus as well as 6 other combined herbal medicines of Group B) and Group C were placebo. Patients should meet all the inclusion criteria: age between 18 and 80 and diagnosis of HICH by brain CT scan between 6 and 72 h from the onset. The CT scan will be taken at four critical time points: baseline, between 6 and 72h, 24h after onset, and between 10 and 14 days after onset. The drug intervention lasts 10 days, and there is a follow-up visit taken after 90 days. The haematoma enlargement after 24 h onset as demonstrated by CT is the primary outcome. Discussion. A large amount of data from high-quality RCTs is needed for the extensive clinical application of herbal medicine. The CRRICHTrial-II will evaluate the safety and effectiveness of ICH-012 in a safer time window between 6 and 72 h and investigate the possible mechanisms of action and direction of herbal medicine in the haematoma growth after HICH. Trial registration at ClinicalTrial.gov, ID: NCT03354026, is registered on 23rd Nov. 2017.

Right-time vs real-time pro-active construction safety and health system architecture

2016 ◽  
Vol 16 (3) ◽  
pp. 253-280 ◽  
Author(s):  
Jochen Teizer
Keyword(s):  
Supply Chain ◽  
Real Time ◽  
Occupational Safety ◽  
Time Window ◽  
Data Gathering ◽  
Critical Time ◽  
Construction Safety ◽  
Content Type ◽  
Safety And Health ◽  
High Concern

Purpose The purpose of this paper is to investigate the critical time window for pro-active construction accident prevention and response. Large to small organisations throughout the entire construction supply chain continue to be challenged to adequately prevent accidents. Construction worker injuries and fatalities represent significant waste of resources. Although the five C’s (culture, competency, communication, controls and contractors) have been focusing on compliance, good practices and best-in-class strategies, even industry leaders have only marginal improvements in recorded safety statistics for many years. Design/methodology/approach Right-time vs real-time construction safety and health identifies three major focus areas to aid in the development of a strategic, as opposed to tactical, response. Occupational safety and health by design, real-time safety and health monitoring and alerts and education, training and feedback leveraging state-of-the-art technology provide meaningful predictive, quantitative and qualitative measures to identify, correlate and eliminate hazards before workers get injured or incidents cause collateral damage. Findings The current state and development of existing innovative initiatives in the occupational construction safety and health domain are identified. A framework for right-time vs real-time construction safety and health presents the specific focus on automated safety and health data gathering, analysis and reporting to achieve better safety performance. The developed roadmap for right-time vs real-time safety and health is finally tested in selected application scenarios of high concern in the construction industry. Originality/value A strategic roadmap to eliminate hazards and accidents through right-time vs real-time automation is presented that has practical as well as social implications on conducting a rigorous safety culture and climate in a construction business and its entire supply chain.

scholarly journals Critical Time-Window for NO–cGMP-Dependent Long-Term Memory Formation after One-Trial Appetitive Conditioning

2002 ◽  
Vol 22 (4) ◽  
pp. 1414-1425 ◽  
Author(s):  
Ildikó Kemenes ◽  
György Kemenes ◽  
Richard J. Andrew ◽  
Paul R. Benjamin ◽  
Michael O'Shea
Keyword(s):  
Time Window ◽  
Critical Time ◽  
Memory Formation ◽  
Long Term Memory ◽  
Appetitive Conditioning ◽  
Term Memory

Blindness short after treatment of acute primary angle closure in China

2020 ◽  
pp. bjophthalmol-2020-316259
Author(s):  
Shuning Li ◽  
Guangxian Tang ◽  
Su Jie Fan ◽  
Gang Zhai ◽  
Jianhua Lv ◽  
...  
Keyword(s):  
Risk Factors ◽  
Time Window ◽  
Case Series ◽  
Critical Time ◽  
Education Level ◽  
Angle Closure ◽  
Retrospective Case ◽  
Acute Primary Angle Closure ◽  
Factors Associated ◽  
Primary Angle Closure

AimsTo study the risk factors associated with blindness after treatment of acute primary angle closure (APAC), and to identify the critical time window to decrease rate of blindness.MethodsIn this multicentre retrospective case series, 1030 consecutive subjects (1164 eyes) with APAC in China were recruited. The rates of blindness were analysed up to 3 months after treatment of APAC. A logistic regression was used to identify the risk factors associated with blindness, including age, gender, distance to hospital, rural or urban settings, treatment method, education level, time from symptom to treatment (TST, hours) and presenting intraocular pressure (IOP). The critical time window associated with a blindness rate of ≤1% was calculated based on a cubic function by fitting TST to the rate of blindness at each time point.ResultsThe rate of blindness after APAC was 12.54% after treatment. In multivariate regression, education level, TST and presenting IOP were risk factors for blindness (p=0.022, 0.004 and 0.001, respectively). The critical time window associated with a blindness rate of ≤1% was 4.6 hours.Conclusions and relevanceEducation level, TST and presenting IOP were risk factors for blindness after APAC. Timely medical treatment is key in reducing blindness after APAC.

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