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Indirect Drive Inertial Confinement Fusion Experiments on the National Ignition Facility (NIF) have achieved a burning plasma state with neutron yields exceeding 170 kJ, roughly 3 times the prior record and a necessary stage for igniting plasmas. The results are achieved despite multiple sources of degradations that lead to high variability in performance. Results shown here, for the first time, include an empirical correction factor for mode-2 asymmetry in the burning plasma regime in addition to previously determined corrections for radiative mix and mode-1. Analysis shows that including these three corrections alone accounts for the measured fusion performance variability in the two highest performing experimental campaigns on the NIF to within error. Here we quantify the performance sensitivity to mode-2 symmetry in the burning plasma regime and apply the results, in the form of an empirical correction to a 1D performance model. Furthermore, we find the sensitivity to mode-2 determined through a series of integrated 2D radiation hydrodynamic simulations to be consistent with the experimentally determined sensitivity only when including alpha-heating.

Abstract Background Disorientation is an early indicator of developing postoperative delirium (POD), which is associated with increased mortality and cognitive decline. The well-established “Confusion-Assessment-Method-for-Intensive-Care-Unit” (CAM-ICU) for diagnosing POD in intubated patients cannot make use of the feature ‘disorientation’, as this requires verbal communication. Other tools such as the 4AT test for disorientation but are not established in ICU settings. We therefore combined test-variables of the CAM-ICU (level of consciousness, fluctuating mental status and inattention) with verbal testing for disorientation to develop and enhance diagnostic accuracy of the “Confusion Assessment Method for Intermediate Care Unit” (CAM-IMC). In the present study we describe the development and the evaluation of the diagnostic accuracy of the CAM-IMC. Methods We conducted a prospective cohort-study to develop and evaluate the diagnostic accuracy of the CAM-IMC and disorientation for diagnosing POD in non-intubated patients undergoing elective cardiac surgery. All patients were eligible during data collection period. Exclusion criteria were preexisting brain-organic disease, age

Young children with visual impairment and their families often require specialized assistance through early intervention to develop adaptive routines, cues, and environmental settings during mealtimes and other daily tasks. There is little empirical data in the area of mealtime routines available to support families of young children with visual impairment, and the need for research-based interventions is great. The purpose of this initial needs assessment survey was to gather information as little is already known about what teachers of students with visual impairment trained in early intervention (TSVI-EIs) and other early interventionists who work with infants and toddlers with visual impairment already know about the development of independent mealtime skills. The results of this survey indicate that early intervention professionals would like additional opportunities to learn about mealtime routine strategies for young children with visual impairment, confirm their current experiences and knowledge, and identify additional training and resources.

The budget of reactive nitrogen species, which play a central role in atmospheric chemistry (e.g. in photochemical O3 production), is poorly understood in forested regions. In this study, through observations of NO, NO2, NOy, and O3 in the Rambouillet Forest near Paris, France, we have examined nighttime processes controlling NOx in an anthropogenically impacted forest environment. The O3 mixing ratios displayed a strong diel profile at the site that was driven by a variable but generally rapid deposition to soil and foliar surfaces. The O3 diel profile was strongly influenced by relative humidity and temperature inversion. Only when the O3 mixing ratio was sufficiently low (and thus the NO lifetime sufficiently long) were sustained NO peaks observed above the instrumental detection limit, enabling the derivation of average NO emission rates of ∼1.4 ppbv h−1 from the soil. Observations of the lack of increase in NO2 at night, despite a significant production rate from the reaction of NO with O3, enabled an effective lifetime of NO2 of ∼0.5–3 h to be derived. As the loss of NO2 was not compensated for by the formation of gas- or particle-phase reactive nitrogen species, it was presumably either driven by deposition to soil and foliar surfaces or any products formed were themselves short-lived with respect to deposition. By comparison, the daytime lifetime of NO2 with respect to loss by reaction with OH is about 1 d. Our results indicate that the nighttime deposition of NO2 is a major sink of boundary layer NOx in this temperate forest environment.

Abstract Myotonic Dystrophy type 1 (DM1), a highly prevalent form of muscular dystrophy, is caused by (CTG)n repeat expansion in the DMPK gene. Much of DM1 research has focused on the effects within the muscle and neurological tissues; however, DM1 patients also suffer from various metabolic and liver dysfunctions such as increased susceptibility to metabolic dysfunction-associated fatty liver disease (MAFLD) and heightened sensitivity to certain drugs. Here, we generated a liver-specific DM1 mouse model that reproduces molecular and pathological features of the disease, including susceptibility to MAFLD and reduced capacity to metabolize specific analgesics and muscle relaxants. Expression of CUG-expanded (CUG)exp repeat RNA within hepatocytes sequestered muscleblind-like proteins and triggered widespread gene expression and RNA processing defects. Mechanistically, we demonstrate that increased expression and alternative splicing of acetyl-CoA carboxylase 1 drives excessive lipid accumulation in DM1 livers, which is exacerbated by high-fat, high-sugar diets. Together, these findings reveal that (CUG)exp RNA toxicity disrupts normal hepatic functions, predisposing DM1 livers to injury, MAFLD, and drug clearance pathologies that may jeopardize the health of affected individuals and complicate their treatment.

Abstract Background Control of humeral torsion can present a challenge, especially intraoperatively during closed reduction and fixation of humeral shaft fractures or 2-part surgical neck fractures of the proximal humerus. The objective of this study is to develop and validate an indirect method for the assessment of humeral torsion using an index that is linearly correlated with rotational arm position and can be derived from only a single plain radiographic image of the proximal humerus. Methods The Humeral Head Offset Index (HHOI) is calculated as the ratio of the medial and lateral offset of the humeral head measured from the outer cortices of the shaft on a plain radiographic or fluoroscopic image. The relationship of HHOI with humeral torsion was first verified on a sawbone model with radiopaque characteristics under fluoroscopic control. Different degrees of retroversion were simulated through manual rotation of the humerus with a digital protractor in 5° increments until 40° internally rotated and then in 5° increments until 40° externally rotated from the neutral position. The same procedure was subsequently performed digitally on Digitally Reconstructed Radiographs (DRRs) from computed tomography (CT) dataset of the sawbone. Next, the HHOI index was applied to eight randomly selected patients with total humerus CT using the same method. Spearman’s rho was calculated for the bivariate analysis of correlation between the simulated degree of retroversion and the HHOI. Strength of correlation was classified according to Koo and Li. Interrater and intrarater reliability of three blinded observers with repetition of measurement after three months were analyzed by assessing the intraclass correlation coefficient (ICC). Results Both in the sawbone model and in DRRs, we demonstrated a high to very high significant linear correlation between simulated retroversion and the HHOI. ICC values demonstrated excellent interrater reliability and excellent intrarater reliability for measurement of the HHOI. Conclusions The HHOI is a new, simple, reliable index that has a linear relationship to the rotation of the humerus and can therefore allow an indirect control of humeral torsion in comparison to the contralateral side.

We present direct measurements of biogenic volatile organic compound (BVOC)-induced nitrate radical (NO3) reactivity (kVOC) through the diel cycle in the suburban, temperate forest of Rambouillet near Paris (France). The data were obtained in a 6-week summer period in 2022 as part of the Atmospheric ChemistRy Of the Suburban foreSt (ACROSS) campaign. kVOC was measured in a small (700 m2) clearing mainly at a height of 5.5 m above ground level but also at 40 m (for 5 d and nights). At nighttime, mean values (and 25th–75th percentile ranges) of knightVOC(5.5m) = (0.24-0.06+0.32) s−1 and knightVOC(40m) = (0.016-0.007+0.018) s−1 indicate a significant vertical gradient and low NO3 reactivity above the canopy, whereas knightVOC(5.5 m) showed peak values of up to 2 s−1 close to the ground. The strong vertical gradient in NO3 reactivity could be confirmed by measurements between 0 and 24 m on one particular night characterized by a strong temperature inversion and is a result of the decoupling of air masses aloft from the ground- and canopy-level sources of BVOCs (and nitric oxide, NO). No strong vertical gradient was observed in the mean daytime NO3 reactivity, with kdayVOC(5.5m) = (0.12 ± 0.04) s−1 for the entire campaign and kdayVOC(40m) = (0.07 ± 0.02) s−1 during the 5 d period. Within the clearing, the fractional contribution of VOCs to the total NO3 loss rate coefficient (ktot, determined by photolysis, reaction with NO and VOCs) was 80 %–90 % during the night and ∼ 50 % during the day. In terms of chemical losses of α-pinene below canopy height in the clearing, we find that at nighttime hydroxyl radicals (OH) and ozone (O3) dominate, with NO3 contributing “only” 17 %, which decreases further to 8.5 % during the day. Based on measured OH, measured O3, and calculated NO3 concentrations, the chemical lifetime of BVOCs at noon is about 1 h and is likely to be longer than timescales of transport out of the canopy (typically of the order of minutes), thus significantly reducing the importance of daytime in-canopy processing. Clearly, in forested regions where sufficient nitric oxide and nitrogen dioxide (NOx) is available, the role of NO3 and OH as initiators of BVOC oxidation is not strictly limited to nighttime and daytime, respectively, as often implied in e.g. atmospheric chemistry textbooks.

Lead (Pb) is a neurotoxicant with early life exposure linked to long-term health effects. Piwi-interacting RNAs (piRNAs) are small non-coding RNAs that associate with PIWIL proteins to induce DNA methylation. It remains unknown whether Pb exposure influences piRNA expression. This study evaluated how perinatal Pb exposure (32 ppm in drinking water) impacts piRNA expression in adult mice and assessed piRNA dysregulation as a potential mechanism for Pb-induced toxicity. Pb exposure effects on piRNA expression and associated gene repression in the germline (testis/ovary) and soma (liver and brain) were evaluated. Small RNA sequencing was used to determine differentially expressed piRNAs, RT-qPCR to examine piRNA target expression, and whole genome bisulfite sequencing to evaluate target DNA methylation status. Three piRNAs (mmpiR-1500602, mmpiR-0201406, and mmpiR-0200026) were significant after multiple testing correction (all downregulated in the male Pb-exposed brain in comparison to control; FDR

Abstract Purpose The aim was to characterize the framework conditions in academic interventional radiology (IR) in Germany with focus on differences between genders. Materials and methods After IRB approval, all members of The German Society for Interventional Radiology and Minimally Invasive Therapy (n = 1,632) were invited to an online survey on work and research. Statistical comparisons were undertaken with the Fisher’s exact test, Wilcoxon rank sum test or Pearson’s Chi-squared test. Results From 267 available questionnaires (general response rate 16.4%), 200 were fully completed. 40% of these (78/200) were involved in research (71% men vs. 29% women, p

Despite being a well-established economic activity in numerous countries in the world, domestic tourism has received relatively little academic exploration, particularly in Namibia. While this study acknowledges the significance of work already done in this field, there remains a general lack of understanding of the factors motivating domestic tourists’ decisions to travel in the study area. As a result, this study aims to understand the key push and pull factors for domestic tourists, using the Erongo region of Namibia as a case study. The study adopts a quantitative research approach through a survey of 400 domestic tourists in the study area. Relaxation and escapism, seeking participatory experiences, and seeking enriching experiences emerged as the three main push factors, while destination attributes, events and activities, safety and familiarity, and variety of experiences were identified as dominant pull factors. The study recommends that tourism planners and marketers tailor tourism offerings to the asserted domestic tourists’ motivations to induce more domestic tourism demand and consumption among domestic tourists.

Background Greenness—or vegetative presence—has been identified as a factor in chronic disease. The present study examines the longitudinal relationship between objective measures of greenness at the residential block level and incidence of 6 cardiovascular disease conditions. Methods and Results Analyses examined the impact of consistently high versus consistently low “precision” greenness at the Census block level on the 5‐year incidence of cardiovascular disease conditions, including acute myocardial infarction, atrial fibrillation, heart failure, ischemic heart disease, stroke/transient ischemic attack, and hypertension, among 229 034 US Medicare beneficiaries in Miami‐Dade County, Florida, USA. Zero‐inflated Poisson regression was used to model the odds of developing any new cardiovascular disease and number of new cardiovascular disease conditions based on greenness tertiles computed across 2011 and 2016 Normalized Difference Vegetation Index values, adjusting for individual age, sex, race, ethnicity, baseline cardiovascular disease conditions, neighborhood income, and walkability in 2011 and 2016. When compared with individuals consistently in the low greenness tertile in 2011 and 2016, those consistently in the high greenness tertile in 2011 and 2016 had a 9% lower odds of having any new cardiovascular conditions (odds ratio [OR], 0.91 [95% CI, 0.84–0.99]; P=0.021). Conclusions Over a 5‐year period, consistently high greenness, when compared with consistently low greenness, was associated with lower odds of any new cardiovascular disease conditions. Identifying the role of greenness exposure in such a small geographic area, the Census block on which the older adult resides, allows for more precise, strategic decisions on where additional trees can be added—by selecting at‐risk blocks rather than entire neighborhoods for tree‐planting interventions.

Effective legislative framework is the cornerstone of managing hazards and disasters because they have become policy problems of global and local concern. This research study aims at understanding the implementation, strengths and gaps of policies related to Eco-DRR in SADC member states. In particular, attempts to critically analyse the making of DRM policies, as well as the variables underpinning these policies, given the high level of disaster losses. A literature survey was conducted to contextualise and conceptualise statutory and policy-based Eco-DRR. Academic literature on Eco-DRR and related policies, journal articles and related policies, official documents in SADC states including policies, acts, legislations, strategies, frameworks and plans were consulted. The analysis revealed that the Eco-DRR approaches have not yet been mainstreamed as part of standards of DRM in most of SADC member states, opting largely on ad hoc practice. Short-term plans and/or strategies don’t help to articulate funding and programme priorities. In addition, irregular updating of policies in some member states and a lack of following up mechanisms were noted. Contribution: To change this reality, it is necessary to include Eco-DRR in strategies and/or plans and to standardise ecosystem-based measures for reducing disaster risks. Additionally, there is an urgent need for empowerment of the existing institutions and creation of networks that are driven by SADC institutions. Overall, it is evident that there is a regional interest and demand to apply and standardise ecosystem-based approaches and natural or green infrastructure solutions toward Eco-DRR.

ObjectiveVasoplegic syndrome remains a common complication of cardiac surgery. It has serious implications for the healthcare system and individual patients, as it leads to rising healthcare costs and higher mortality. A better understanding of factors triggering vasoplegic syndrome is essential for the development of effective prevention strategies. We aimed to identify clinical characteristics and intraoperative parameters associated with the development of vasoplegic syndrome in coronary artery bypass graft surgery and the influence of vasoplegia on outcome.MethodsWe retrospectively analyzed the data of all patients who underwent isolated coronary artery bypass graft surgery or coronary artery bypass graft surgery combined with atrial appendage occlusion, using the heart-lung machine at our institution from 04/2019 to 12/2020. Vasoplegic syndrome was defined as MAP ≤60 mmHg and norepinephrine equivalence dosage of ≥0.2 μg/kg/min with a central venous saturation ≥60% within 2 days from surgery.ResultsOf 647 patients included in this study, 72 (11.1%) developed vasoplegic syndrome. Patients experiencing vasoplegia had longer stay in ICU, more frequently underwent tracheostomy and suffered more often from pneumonia. The duration of extracorporeal circulation, intraoperative application of platelet concentrates and usage of cold crystalloid cardioplegia (Bretschneider) independently predicted development of vasoplegic syndrome.ConclusionsEven in relatively low-risk cardiac surgery, vasoplegic syndrome is a common complication and was associated with serious adverse effects. The use of warm blood cardioplegia (Calafiore) seems to be safer than cold crystalloid cardioplegia (Bretschneider) and might be preferable in patients that are vulnerable to the consequences of vasoplegic syndrome.

Abstract Indirect Drive Inertial Confinement Fusion Experiments on the National Ignition Facility (NIF) have achieved a burning plasma state with neutron yields exceeding 170 kJ, roughly 3 times the prior record and a necessary stage for igniting plasmas. The results are achieved despite multiple sources of degradations that lead to high variability in performance. Results shown here, for the first time, include an empirical correction factor for mode-2 asymmetry in the burning plasma regime in addition to previously determined corrections for radiative mix and mode-1. Analysis shows that including these three corrections alone accounts for the measured fusion performance variability in the two highest performing experimental campaigns on the NIF to within error. Here we quantify the performance sensitivity to mode-2 symmetry in the burning plasma regime and apply the results, in the form of an empirical correction to a 1D performance model. Furthermore, we find the sensitivity to mode-2 determined through a series of integrated 2D radiation hydrodynamic simulations to be consistent with the experimentally determined sensitivity only when including alpha-heating.

Abstract Background Adults with congenital heart defects (ACHD) globally constitute a notably medically underserved patient population. Despite therapeutic advancements, these individuals often confront substantial physical and psychosocial residua or sequelae, requiring specialized, integrative cardiological care throughout their lifespan. Heart failure (HF) is a critical challenge in this population, markedly impacting morbidity and mortality. Aims The primary aim of this study is to establish a comprehensive, prospective registry to enhance understanding and management of HF in ACHD. Named PATHFINDER-CHD, this registry aims to establish foundational data for treatment strategies as well as the development of rehabilitative, prehabilitative, preventive, and health-promoting interventions, ultimately aiming to mitigate the elevated morbidity and mortality rates associated with congenital heart defects (CHD). Methods This multicenter survey will be conducted across various German university facilities with expertise in ACHD. Data collection will encompass real-world treatment scenarios and clinical trajectories in ACHD with manifest HF or at risk for its development, including those undergoing medical or interventional cardiac therapies, cardiac surgery, inclusive of pacemaker or ICD implantation, resynchronization therapy, assist devices, and those on solid organ transplantation. Design The study adopts an observational, exploratory design, prospectively gathering data from participating centers, with a focus on patient management and outcomes. The study is non-confirmatory, aiming to accumulate a broad spectrum of data to inform future hypotheses and studies. Processes Regular follow-ups will be conducted, systematically collecting data during routine clinical visits or hospital admissions, encompassing alterations in therapy or CHD-related complications, with visit schedules tailored to individual clinical needs. Assessments Baseline assessments and regular follow-ups will entail comprehensive assessments of medical history, ongoing treatments, and outcomes, with a focus on HF symptoms, cardiac function, and overall health status. Discussion of the design The design of the PATHFINDER-CHD Registry is tailored to capture a wide range of data, prioritizing real-world HF management in ACHD. Its prospective nature facilitates longitudinal data acquisition, pivotal for comprehending for disease progression and treatment impacts. Conclusion The PATHFINDER-CHD Registry is poised to offer valuable insights into HF management in ACHD, bridging current knowledge gaps, enhancing patient care, and shaping future research endeavors in this domain.

Abstract Background Amidst the COVID-19 pandemic, vaccination has been a crucial strategy for mitigating transmission and disease severity. However, vaccine-effectiveness may be influenced by various factors, including booster vaccination, as well as personal factors such as age, sex, BMI, smoking, and comorbidities. To investigate the potential effects of these factors on SARS-CoV-2 infection and disease severity, we analyzed data from the third round of the Cologne Corona Surveillance (CoCoS) project, a large cross-sectional survey. Methods The study was conducted mid-February to mid-March 2022 in Cologne, Germany. A random sample of 10,000 residents aged 18 years and older were invited to participate in an online survey. Information on participants’ demographics (age, sex), SARS-CoV-2 infections, vaccination status, smoking, and preexisting medical conditions were collected. The outcomes of the study were: (1) the occurrence of SARS-CoV-2 infection despite vaccination (breakthrough infection) and (2) the occurrence of moderate-to-severe disease as a result of a breakthrough infection. Cox proportional-hazards regression was used to investigate possible associations between the presence/absence of booster vaccination, personal factors and the occurrence of SARS-CoV-2 infection. Associations with moderate-to-severe infection were analyzed using the Fine and Gray subdistribution hazard model. Results A sample of 2,991 residents responded to the questionnaire. A total of 2,623 primary immunized participants were included in the analysis of breakthrough infection and 2,618 in the analysis of SARS-CoV-2 infection severity after exclusions due to incomplete data. The multivariable results show that booster vaccination (HR = 0.613, 95%CI 0.415–0.823) and older age (HR = 0.974, 95%CI 0.966–0.981) were associated with a reduced hazard of breakthrough infection. Regarding the severity of breakthrough infection, older age was associated with a lower risk of moderate-to-severe breakthrough infection (HR = 0.962, 95%CI0.949–0.977). Female sex (HR = 2.570, 95%CI1.435–4.603), smoking (HR = 1.965, 95%CI1.147–3.367) and the presence of chronic lung disease (HR = 2.826, 95%CI1.465–5.450) were associated with an increased hazard of moderate-to-severe breakthrough infection. Conclusion The results provide a first indication of which factors may be associated with SARS-CoV-2 breakthrough infection and moderate-to-severe course of infection despite vaccination. However, the retrospective nature of the study and risk of bias in the reporting of breakthrough infection severity limit the strength of the results. Trial registration DRKS.de, German Clinical Trials Register (DRKS), Identifier: DRKS00024046, Registered on 25 February 2021.

Background: There are various experimental measurement techniques used to measure residual stress and this work describes one such method, the slotting method, and its application to measure near surface residual stresses. Objective: This work examines its application to macro-scale specimens. Methods: A series of numerical experiments were performed to understand the size required to assume that the specimen is infinitely large, namely the thickness, width, and height. To assess measurement repeatability, 12 slotting measurements were performed in a shot peened aluminum plate. Results: The numerical experiments determined the specimen should have a thickness greater than or equal to 21.6 mm (0.85 in), a total specimen width (normal to the slot length) greater than or equal to 44.5 mm (1.75 in), and total height (parallel to the slot) greater than or equal to 38.1 mm (1.5 in) for the specimen to be assumed to be infinite. Slotting measurement repeatability was found to have a maximum repeatability standard deviation of 30 MPa at the surface that decays rapidly to 5 MPa at a depth of 0.3 mm from the surface. Comparison x-ray diffraction measurements were performed. Conclusions: Infinite plate dimensions and slot length were determined as well as measurement repeatability. Slotting was shown to have significantly better repeatability than X-ray diffraction with layer removal for this application.