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In functional magnetic resonance imaging (fMRI), the blood oxygenation level dependent (BOLD) signal is often interpreted as a measure of neural activity. However, because the BOLD signal reflects the complex interplay of neural, vascular, and metabolic processes, such an interpretation is not always valid. There is growing evidence that changes in the baseline neurovascular state can result in significant modulations of the BOLD signal that are independent of changes in neural activity. This paper introduces some of the normalization and calibration methods that have been proposed for making the BOLD signal a more accurate reflection of underlying brain activity for human fMRI studies.
This study investigates practicing clinician and staff perspectives on potential protocol modifications for the “Nasal Irrigation, Oral Antibiotics, and Subgroup Targeting for Effective Management of Acute Sinusitis” (NOSES) study, a pragmatic randomized controlled trial aiming at improving acute rhinosinusitis management. Focus groups with clinicians and staff at the pretrial stage recommended expanding participant age inclusion criteria, incorporating patients with COVID-19, and shortening the supportive care phase. Participants also discussed patient engagement and recruitment strategies. These practical insights contribute to optimizing the NOSES trial design and underscore the value of qualitative inquiries and healthcare stakeholder engagement in informing clinical trial design.
One species-general life history (LH) principle posits that challenging childhood environments are coupled with a fast or faster LH strategy and associated behaviors, while secure and stable childhood environments foster behaviors conducive to a slow or slower LH strategy. This coupling between environments and LH strategies is based on the assumption that individuals’ internal traits and states are independent of their external surroundings. In reality, individuals respond to external environmental conditions in alignment with their intrinsic vitality, encompassing both physical and mental states. The present study investigated attachment as an internal mental state, examining its role in mediating and moderating the association between external environmental adversity and fast LH strategies. A sample of 1169 adolescents (51% girls) from 9 countries was tracked over 10 years, starting from age 8. The results confirm both mediation and moderation and, for moderation, secure attachment nullified and insecure attachment maintained the environment-LH coupling. These findings suggest that attachment could act as an internal regulator, disrupting the contingent coupling between environmental adversity and a faster pace of life, consequently decelerating human LH.
Adolescents with depression have distinct affective reactions to daily events, but current research is controversial. The emotional context insensitivity theory suggests blunted reactivity in depression, whereas the hypotheses of negative potentiation and mood brightening effect suggest otherwise. While nonlinear associations between depression severity and affective reactivity have been observed, studies with a separate subclinical group remain rare. Subthreshold depression (SD), defined by two to four symptoms lasting for two weeks or more, provides a dimensional view to the underpinnings of affective reactivity. In this study, we compared positive affect (PA) and negative affect (NA) reactivity to positive and negative daily events (uplifts and stress) among adolescents with Major Depressive Disorder (MDD), SD and healthy controls (HC) using experience sampling methods (ESM).
Objectives
We hypothesized a stepped difference in affective reactivity along the depression spectrum: the MDD group will have the strongest reactivity of PA and NA to uplifts and stress, followed by SD and HC.
Methods
Three groups (MDD, SD, and HC) of adolescents were recruited from an epidemiologic sample entitled ‘Hong Kong Child and Adolescent Psychiatric Epidemiologic Survey: Age 6 to 17’. Group status was determined by the Diagnostic Interview Schedule for Children Version 5. They completed an experience sampling diary on smartphone for 14 consecutive days, with 5-10 entries per day. Momentary levels of PA (happy, relaxed, contented), NA (irritated, low, nervous), uplifts and stress experienced before the entry were measured on a 1-7 Likert scale.
Results
The sample consisted of 19 adolescents with MDD, 30 with SD, and 59 HC. The M:F ratio was 17:19. The age range was 12-18 with a mean of 14.8. The overall ESM completion rate was 46%. The MDD group had the highest levels of stress and NA, and the lowest levels of uplifts and PA, followed by the SD and HC groups respectively (p<0.01). Across groups, levels of PA were positively associated with uplifts and negatively associated with stress, whereas levels of NA were positively associated with stress and negatively associated with uplifts. The Group x Uplift interaction effect on PA was significant, with greater PA reactivity in SD (p<0.01) and MDD (p=0.07) when compared with HC. The Group x Uplift interaction effect on NA was significant, with greater NA reactivity in SD than HC (p<0.01). The Group x Stress interaction effect on PA was significant, with greater PA reactivity in SD than HC (p<0.01) and MDD (p<0.01). The Group x Stress interaction effect with NA is non-significant.
Conclusions
Contrary to our hypothesis, adolescents with SD experienced strongest PA and NA reactivity in uplifts and PA reactivity in stress. It provides evidence towards a nonlinear relationship between severity of depression and affective reactivity.
Background: Hyperacute stroke care demands rapid, coordinated care. Traditional metrics like Door-to-Needle time are pivotal but insufficient for capturing the complexity of endovascular stroke interventions. The SMILES collaboration aims to standardize and optimize protocols for door-to-intervention times, incorporating Crew Resource Management (CRM). Methods: The multidisciplinary initiative integrates both hospitals, ED, neurology, and QI teams. We employed a comprehensive approach: stakeholder engagement, simulation-based learning, process mapping, and literature review. Emphasis was placed on enhancing situational awareness, triage and prioritization, cognitive load management, role clarity, effective communication, and debriefing. Results: The collaboration led to PDSA cycles and development of refined stroke protocols. Interventions included: 1) A ’zero point survey’ for team pre-arrival briefings, enhancing situational awareness and role clarity; 2) Streamlined patient registration to reduce cognitive load and improve triage efficiency; 3) Direct transfer of patients to imaging. Additionally, digital tools were implemented to facilitate communication. Simulation sessions reinforced CRM principles, leading to improved team cohesion and operational performance. Conclusions: The SMILES initiative is grounded in CRM principles by standardizing protocols and emphasizing non-technical skills crucial for high-stakes environments. This improves outcomes but also fosters a culture of safety and efficiency. Future directions include an evaluation of these protocols’ impact on patient factors.
Ultrafast optical probing is a widely used method of underdense plasma diagnostic. In relativistic plasma, the motion blur limits spatial resolution in the direction of motion. For many high-power lasers the initial pulse duration of 30–50 fs results in a 10–15 μm motion blur, which can be reduced by probe pulse post-compression. Here we used the compression after compressor approach [Phys.-Usp. 62, 1096 (2019); JINST 17 P07035 (2022)], where spectral broadening is performed in thin optical plates and is followed by reflections from negative-dispersion mirrors. Our initially low-intensity probe beam was down-collimated for a more efficient spectral broadening and higher probe-to-self-emission intensity ratio. The setup is compact, fits in a vacuum chamber and can be implemented within a short experimental time slot. We proved that the compressed pulse retained the high quality necessary for plasma probing.
The Sinya Beds of the Amboseli Basin in Tanzania and Kenya consist largely of carbonate rocks and Mg-rich clays that are intensely deformed where exposed in and near former meerschaum mines. The carbonate rocks consist of limestone and dolomite in Tanzania, but only dolomite has been identified in Kenya. Sepiolite and mixed-layered kerolite/stevensite (Ke/St) are subordinate constituents of the carbonate rocks. The carbonate rocks and overlying bedded sepiolite were deposited in a semiarid lake basin at the foot of the large volcano Kilimanjaro. Calcite and dolomite of the carbonate rocks have δ18O values 4–6‰ lower than calcite and dolomite of the late Pleistocene Amboseli Clays, suggesting that the Sinya Beds were deposited in the middle or early Pleistocene under a different climatic regime when meteoric water had lower δ18O values than at present.
Mg-rich clay minerals form veins and fill cavities in the Sinya Beds. The principal clay minerals are sepiolite and Ke/St, some of which contains substantial Al and Fe (Al-Ke/St). NEWMOD® modeling and other X-ray diffraction (XRD) data suggest that most of the Ke/St contains 25–50 percent kerolite layers, but minor amounts of kerolite-rich Ke/St are present in some samples. Illite with an inferred high content of Fe or Mg is a minor constituent of the samples with Al-Ke/St. The cavity-filling clays were chemically precipitated, as shown by field relationships and SEM study. The early-deposited clays of veins and cavities are principally Ke/St with minor sepiolite, and the latest clay is sepiolite (meerschaum), generally with minor Ke/St.
The δ18O values of cavity-filling Ke/St range from 22.5–25.6‰ and correlate with mineral composition, with the highest values associated with the highest content of stevensite and the lowest values with the highest content of kerolite. This relation suggests that high salinities favored stevensite and low salinities favored kerolite. δ18O values of sepiolite (meerschaum) fall in the middle of the range for Ke/St, suggesting that salinity was not the main control on sepiolite precipitation. High values of may have been a major factor in sepiolite precipitation.
Different mixtures of dilute ground water and saline, alkaline lake water in pore fluids may largely account for the differences in clay mineralogy of cavity-filling clays. Sepiolite is the dominant clay mineral in lacustrine sediments of the Amboseli Basin, and the cavity-filling sepiolite may reflect a high proportion of lake water. The low-Al Ke/St may have formed from fluids with a higher proportion of ground water. Detrital clay was very likely a factor in forming the Al-Ke/St, for which δ18O values suggest a saline environment.
It is unclear how much adolescents’ lives were disrupted throughout the COVID-19 pandemic or what risk factors predicted such disruption. To answer these questions, 1,080 adolescents in 9 nations were surveyed 5 times from March 2020 to July 2022. Rates of adolescent COVID-19 life disruption were stable and high. Adolescents who, compared to their peers, lived in nations with higher national COVID-19 death rates, lived in nations with less stringent COVID-19 mitigation strategies, had less confidence in their government’s response to COVID-19, complied at higher rates with COVID-19 control measures, experienced the death of someone they knew due to COVID-19, or experienced more internalizing, externalizing, and smoking problems reported more life disruption due to COVID-19 during part or all of the pandemic. Additionally, when, compared to their typical levels of functioning, adolescents experienced spikes in national death rates, experienced less stringent COVID-19 mitigation measures, experienced less confidence in government response to the COVID-19 pandemic, complied at higher rates with COVID-19 control measures, experienced more internalizing problems, or smoked more at various periods during the pandemic, they also experienced more COVID-19 life disruption. Collectively, these findings provide new insights that policymakers can use to prevent the disruption of adolescents’ lives in future pandemics.
The target backsheath field acceleration mechanism is one of the main mechanisms of laser-driven proton acceleration (LDPA) and strongly depends on the comprehensive performance of the ultrashort ultra-intense lasers used as the driving sources. The successful use of the SG-II Peta-watt (SG-II PW) laser facility for LDPA and its applications in radiographic diagnoses have been manifested by the good performance of the SG-II PW facility. Recently, the SG-II PW laser facility has undergone extensive maintenance and a comprehensive technical upgrade in terms of the seed source, laser contrast and terminal focus. LDPA experiments were performed using the maintained SG-II PW laser beam, and the highest cutoff energy of the proton beam was obviously increased. Accordingly, a double-film target structure was used, and the maximum cutoff energy of the proton beam was up to 70 MeV. These results demonstrate that the comprehensive performance of the SG-II PW laser facility was improved significantly.
The great demographic pressure brings tremendous volume of beef demand. The key to solve this problem is the growth and development of Chinese cattle. In order to find molecular markers conducive to the growth and development of Chinese cattle, sequencing was used to determine the position of copy number variations (CNVs), bioinformatics analysis was used to predict the function of ZNF146 gene, real-time fluorescent quantitative polymerase chain reaction (qPCR) was used for CNV genotyping and one-way analysis of variance was used for association analysis. The results showed that there exists CNV in Chr 18: 47225201-47229600 (5.0.1 version) of ZNF146 gene through the early sequencing results in the laboratory and predicted ZNF146 gene was expressed in liver, skeletal muscle and breast cells, and was amplified or overexpressed in pancreatic cancer, which promoted the development of tumour through bioinformatics. Therefore, it is predicted that ZNF146 gene affects the proliferation of muscle cells, and then affects the growth and development of cattle. Furthermore, CNV genotyping of ZNF146 gene was three types (deletion type, normal type and duplication type) by Real-time fluorescent quantitative PCR (qPCR). The association analysis results showed that ZNF146-CNV was significantly correlated with rump length of Qinchuan cattle, hucklebone width of Jiaxian red cattle and heart girth of Yunling cattle. From the above results, ZNF146-CNV had a significant effect on growth traits, which provided an important candidate molecular marker for growth and development of Chinese cattle.
We report the experimental results of the commissioning phase in the 10 PW laser beamline of the Shanghai Superintense Ultrafast Laser Facility (SULF). The peak power reaches 2.4 PW on target without the last amplifying during the experiment. The laser energy of 72 ± 9 J is directed to a focal spot of approximately 6 μm diameter (full width at half maximum) in 30 fs pulse duration, yielding a focused peak intensity around 2.0 × 1021 W/cm2. The first laser-proton acceleration experiment is performed using plain copper and plastic targets. High-energy proton beams with maximum cut-off energy up to 62.5 MeV are achieved using copper foils at the optimum target thickness of 4 μm via target normal sheath acceleration. For plastic targets of tens of nanometers thick, the proton cut-off energy is approximately 20 MeV, showing ring-like or filamented density distributions. These experimental results reflect the capabilities of the SULF-10 PW beamline, for example, both ultrahigh intensity and relatively good beam contrast. Further optimization for these key parameters is underway, where peak laser intensities of 1022–1023 W/cm2 are anticipated to support various experiments on extreme field physics.
Background: Chordomas are rare malignant skull-base/spine cancers with devastating neurological morbidities and mortality. Unfortunately, no reliable prognostic factors exist to guide treatment decisions. This work identifies DNA methylation-based prognostic chordoma subtypes that are detectable non-invasively in plasma. Methods: Sixty-eight tissue samples underwent DNA methylation profiling and plasma methylomes were obtained for available paired samples. Immunohistochemical staining and publicly available methylation and gene expression data were utilized for validation. Results: Unsupervised clustering identified two prognostic tissue clusters (log-rank p=0.0062) predicting disease-specific survival independent of clinical factors (Multivariable Cox: HR=16.5, 95%CI: 2.8-96, p=0.0018). The poorer-performing cluster showed immune-related pathway promoter hypermethylation and higher immune cell abundance within tumours, which was validated with external RNA-seq data and immunohistochemical staining. The better-performing cluster showed higher tumour cellularity. Similar clusters were seen in external DNA methylation data. Plasma methylome-based models distinguished chordomas from differential diagnoses in independent testing sets (AUROC=0.84, 95%CI: 0.52-1.00). Plasma methylomes were highly correlated with tissue-based signals for both clusters (r=0.69 & 0.67) and leave-one-out models identified the correct cluster in all plasma cases. Conclusions: Prognostic molecular chordoma subgroups are for the first time identified, characterized, and validated. Plasma methylomes can detect and subtype chordomas which may transform chordoma treatment with personalized approaches tailored to prognosis.
Large-eddy simulations of turbulent flow in partially filled pipes are conducted to investigate the effect of secondary currents on the friction factor, first- and second-order statistics and large-scale turbulent motion. The method is validated first and simulated profiles of the mean streamwise velocity, normal stresses and turbulent kinetic energy (TKE) are shown to be in good agreement with experimental data. The secondary flow is stronger in half- and three-quarters full pipes compared with quarter full or fully filled pipe flows, respectively. The origin of the secondary flow is examined by both the TKE budget and the steamwise vorticity equation, providing evidence that secondary currents originate from the corner between the free surface and the pipe walls, which is where turbulence production is larger than the sum of the remaining terms of the TKE budget. An extra source of streamwise vorticity production is found at the free surface near the centreline bisector, due to the two-component asymmetric turbulence there. The occurrence of dispersive stresses (due to secondary currents) reduces the contribution of the turbulent shear stress to the friction factor, which results in a reduction of the total friction factor of flows in half and three-quarters full pipes in comparison to a fully filled pipe flow. Furthermore, the presence of significant secondary currents inhibits very-large-scale motion (VLSM), which in turn reduces the strength and scales of near-wall streaks. Subsequently, near-wall coherent structures generated by streak instability and transient growth are significantly suppressed. The absence of VLSM and less coherent near-wall turbulence structures is supposedly responsible for the drag reduction in partially filled pipe flows relative to a fully filled pipe flow at an equivalent Reynolds number.
Experiments are conducted in a wave tank to investigate wave scattering by a three-dimensional submerged horizontal rectangular plate in a channel. The free-surface elevation around the plate is presented for various water depths and depths of submergence of the plate. The wave forces and moments are obtained using an underwater load measuring system. The numerical simulations are performed with a parallelized three-dimensional boundary element method. The numerical set-up follows closely the set-up of the laboratory experiments. The numerical results are compared with the experimental results for non-breaking waves. In most cases a good agreement is found for the free-surface elevation, the vertical force and the moment. A physical interpretation of the flow around the plate is provided. The pressure distribution on the lower surface of the plate differs from the linear distribution from the leading edge to the trailing edge that is obtained in the equivalent two-dimensional problem. The reflection by the lateral walls is investigated.
Background: We describe an infant with a diagnosis of GM3 synthase deficiency, presenting with severe neuroirritability from birth. He required multiple admissions due to extreme agitation and caregiver burnout. Multiple pharmacological agents were tried, and the effect of each medication was modest and short-lasting at best. The literature on the management of neuroirritability in children with progressive genetic and metabolic conditions is sparse, and a neuroirritability management protocol has yet to be developed at our institution. Methods: We searched for relevant primary research and articles on PubMed. We reviewed the evidence of each pharmacological agent and added non-pharmacological strategies. We developed management guidelines for neuroirritability at our hospital. This protocol was reviewed by several pediatric neurologists and pediatric palliative care specialists at the Stollery and SickKids Hospitals. Results: We present the Pediatric Neuroirritability Management Protocol for the Stollery Children’s Hospital. Conclusions: Further study is required to assess whether this protocol can be adapted to treat irritability in the context of other neurological conditions such as hypoxic-ischemic encephalopathy and non-accidental injury. In addition, we will expand our guidelines to include other symptoms such as spasticity, dystonia, and autonomic dysfunction.
Prior to the COVID-19 pandemic, adolescents (N = 1,330; Mages = 15 and 16; 50% female), mothers, and fathers from nine countries (China, Colombia, Italy, Jordan, Kenya, Philippines, Sweden, Thailand, United States) reported on adolescents’ internalizing and externalizing problems, adolescents completed a lab-based task to assess tendency for risk-taking, and adolescents reported on their well-being. During the pandemic, participants (Mage = 20) reported on changes in their internalizing, externalizing, and substance use compared to before the pandemic. Across countries, adolescents’ internalizing problems pre-pandemic predicted increased internalizing during the pandemic, and poorer well-being pre-pandemic predicted increased externalizing and substance use during the pandemic. Other relations varied across countries, and some were moderated by confidence in the government’s handling of the pandemic, gender, and parents’ education.
High-energy and high-intensity lasers are essential for pushing the boundaries of science. Their development has allowed leaps forward in basic research areas, including laser–plasma interaction, high-energy density science, metrology, biology and medical technology. The Helmholtz International Beamline for Extreme Fields user consortium contributes and operates two high-peak-power optical lasers using the high energy density instrument at the European X-ray free electron laser (EuXFEL) facility. These lasers will be used to generate transient extreme states of density and temperature to be probed by the X-ray beam. This paper introduces the ReLaX laser, a short-pulse high-intensity Ti:Sa laser system, and discusses its characteristics as available for user experiments. It will also present the first experimental commissioning results validating its successful integration into the EuXFEL infrastructure and viability as a relativistic-intensity laser driver.
Coronavirus disease 2019 (COVID-19) vaccination effectiveness in healthcare personnel (HCP) has been established. However, questions remain regarding its performance in high-risk healthcare occupations and work locations. We describe the effect of a COVID-19 HCP vaccination campaign on SARS-CoV-2 infection by timing of vaccination, job type, and work location.
Methods:
We conducted a retrospective review of COVID-19 vaccination acceptance, incidence of postvaccination COVID-19, hospitalization, and mortality among 16,156 faculty, students, and staff at a large academic medical center. Data were collected 8 weeks prior to the start of phase 1a vaccination of frontline employees and ended 11 weeks after campaign onset.
Results:
The COVID-19 incidence rate among HCP at our institution decreased from 3.2% during the 8 weeks prior to the start of vaccinations to 0.38% by 4 weeks after campaign initiation. COVID-19 risk was reduced among individuals who received a single vaccination (hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.40–0.68; P < .0001) and was further reduced with 2 doses of vaccine (HR, 0.17; 95% CI, 0.09–0.32; P < .0001). By 2 weeks after the second dose, the observed case positivity rate was 0.04%. Among phase 1a HCP, we observed a lower risk of COVID-19 among physicians and a trend toward higher risk for respiratory therapists independent of vaccination status. Rates of infection were similar in a subgroup of nurses when examined by work location.
Conclusions:
Our findings show the real-world effectiveness of COVID-19 vaccination in HCP. Despite these encouraging results, unvaccinated HCP remain at an elevated risk of infection, highlighting the need for targeted outreach to combat vaccine hesitancy.
This chapter uses evidence from the Parenting across Cultures (PAC) project to illustrate ways in which longitudinal data can help achieve the Sustainable Development Goals (SDGs; https://sustainabledevelopment.un.org/). The chapter begins by providing an overview of the research questions that have guided PAC as well as a description of the participants, procedures and measures. Next, empirical findings from PAC are summarized to illustrate implications for six specific SDGs. Then the chapter describes how longitudinal data offer advantages over cross-sectional data in operationalizing SDG targets and implementing the SDGs. Finally, limitations, future research directions and conclusions are provided.
PAC was developed in response to concerns that understanding of parenting and child development was biased by the predominant focus in the literature on studying families in Western, educated, industrialized, rich and democratic (WEIRD) societies and that findings in such countries may not generalize well to more diverse populations around the world (Henrich et al, 2010). In an analysis of the sample characteristics in the most influential journals in six subdisciplines of psychology from 2003 to 2007, 96% of research participants were from Western industrialized countries, and 68% were from the United States alone (Arnett, 2008), which means that 96% of research participants in these psychological studies were from countries with only 12% of the world's population (Henrich et al, 2010). When basic science research is limited to WEIRD countries, knowledge of human development becomes defined by a set of experiences that may not be widely shared in different cultural contexts, so studying parenting and child development in a wide range of diverse cultural contexts is important to understand development more fully.
PAC has been conceptualized and funded as a consecutive series of three five-year grants, each covering a different developmental period and guided by different research questions. In the first project period, participants were aged 8 to 12. The main research questions focused on cultural differences in links between discipline and child adjustment, warmth as a moderator of links between harsh discipline and child outcomes, and cognitive and emotional mediators of effects of harsh discipline on children's aggression and anxiety. In the second period, target participants were 13 to 17 years old.
This study was a retrospective multicentre cohort study of patients with coronavirus disease 2019 (COVID-19) diagnosed at 24 hospitals in Jiangsu province, China as of 15 March 2020. The primary outcome was the occurrence of acute respiratory failure during hospital stay. Of 625 patients, 56 (9%) had respiratory failure. Some selected demographic, epidemiologic, clinical and laboratory features as well as radiologic features at admission and treatment during hospitalisation were significantly different in patients with and without respiratory failure. The multivariate logistic analysis indicated that age (in years) (odds ratio [OR], 1.07; 95% confidence interval [CI]: 1.03–1.10; P = 0.0002), respiratory rate (breaths/minute) (OR, 1.23; 95% CI: 1.08–1.40; P = 0.0020), lymphocyte count (109/l) (OR, 0.18; 95% CI: 0.05–0.69; P = 0.0157) and pulmonary opacity score (per 5%) (OR, 1.38; 95% CI: 1.19–1.61; P < 0.0001) at admission were associated with the occurrence of respiratory failure. Older age, increased respiratory rate, decreased lymphocyte count and greater pulmonary opacity score at admission were independent risk factors of respiratory failure in patients with COVID-19. Patients having these risk factors need to be intensively managed during hospitalisation.