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New drugs to target different pathways in pulmonary hypertension has resulted in increased combination therapy, but details of this use in infants are not well described. In this large multicenter database study, we describe the pharmacoepidemiology of combination pulmonary vasodilator therapy in critically ill infants.
Methods:
We identified inborn infants discharged home from a Pediatrix neonatal ICU from 1997 to 2020 exposed to inhaled nitric oxide, sildenafil, epoprostenol, or bosentan for greater than two consecutive days. We compared clinical variables and drug utilisation between infants receiving simultaneous combination and monotherapy. We reported each combination’s frequency, timing, and duration and graphically represented drug use over time.
Results:
Of the 7681 infants that met inclusion criteria, 664 (9%) received combination therapy. These infants had a lower median gestational age and birth weight, were more likely to have cardiac and pulmonary anomalies, receive cardiorespiratory support, and had higher in-hospital mortality than those receiving monotherapy. Inhaled nitric oxide and sildenafil were most frequently used, and utilisation of combination and monotherapy for all drugs increased over time. Inhaled nitric oxide and epoprostenol were used in infants with a higher gestational age, earlier postnatal age, and shorter duration than sildenafil and bosentan. Dual therapy with inhaled nitric oxide and sildenafil was the most common combination therapy.
Conclusion:
Our study revealed an increased use of combination pulmonary vasodilator therapy, favouring inhaled nitric oxide and sildenafil, yet with considerable practice variation. Further research is needed to determine the optimal combination, sequence, dosing, and disease-specific indications for combination therapy.
Awareness of agricultural climate impacts is growing. In the European Union (EU), the agricultural sector is responsible for significant greenhouse gas emissions while continuing to receive considerable EU budgetary support. A large share of agricultural emissions is linked to livestock husbandry, a sector the direct and indirect climate impacts of which the EU's ‘green’ agricultural policies have historically ignored. This blind spot extends to the sizeable global deforestation footprint from EU livestock feed imports that remains unaddressed, despite the EU's aspired status as a global climate leader and major global agricultural market player. This article benchmarks the evolution of EU agri-climate legal and policy developments, using livestock emissions as a case study to highlight the importance of learning from the successes and failures of the EU experience, to realize future attempts to tackle global agricultural emissions.
Early life adversity (ELA) and youth chronic health conditions have been examined as separate contributors to psychopathology. However, little work has specifically examined early life health adversity (ELHA) and its association with risk for internalizing disorders. This study seeks to examine the relationship between ELHA and internalizing disorders across adolescence. A sample of 705 Australian mother–youth dyads participated in a prospective longitudinal study. Mothers reported child health indicators at youth ages three-to-four days, six months, and five years and completed a psychiatric interview at 15 years. Youth completed a psychiatric interview, as well as measures of current health status, at age 20. ELHA was positively associated with both youth anxiety and depressive disorders from ages 15 to 20. When independently accounting for the role of (a) current health status and (b) exposure to traditionally conceptualized forms of ELA, these findings remained statistically significant for anxiety but not depressive disorders. ELHA interacted with maternal depression, such that ELHA was only associated with youth depressive disorders in cases where mothers themselves had experienced depression. Routine mental health screenings may be warranted for youth who experience ELHA and their mothers. Pediatric primary care may be an ideal setting for implementing prevention and intervention efforts.
We report a numerical investigation of a previously noticed but less explored flow state transition in two-dimensional turbulent Rayleigh–Bénard convection. The simulations are performed in a square domain over a Rayleigh number range of $10^7 \leq Ra \leq 2 \times 10^{11}$ and a Prandtl number range of $0.25 \leq Pr \leq 20$. The transition is characterized by the emergence of multiple satellite eddies with increasing $Ra$, which orbit around and interact with the main vortex roll in the system. Consequently, the main roll is squeezed to a smaller size compared with the domain and wanders around in the bulk region irregularly and extensively. This is in sharp contrast to the flow state before the transition, which is featured by a domain-sized circulatory roll with its vortex centre ‘condensed’ near the domain's centre. Detailed velocity field analysis reveals that there exists an abrupt increase in the energy fluctuations of the Fourier modes during the transition. Based on this phase-transition-like signal, the critical condition for the transition is found to follow a scaling relation as $Ra_t \sim Pr^{1.41}$ where $Ra_t$ is the critical Rayleigh number for the transition. This scaling relation is quantitatively explained by a phenomenological model grounded on the bistability behaviour (i.e. spontaneous and stochastic switching between the two flow states) observed at the edge of the transition. The model can also account for the effects of aspect ratio on the transition reported in the literature (van der Poel et al., Phys. Fluids, vol. 24, 2012).
Social Darwinism was a pathbreaker in the history of Chinese international thought. In this study, we explore the hitherto sparsely discussed process of the reception of social Darwinism in China, which led to a fundamental transformation in Chinese thinking about the international order and the position of China vis-à-vis Western powers. Drawing on the work of three leaders of that intellectual transformation – Yan Fu, Kang Youwei, and Liang Qichao – we analyse issues such as the struggle for existence and survival, national and racial competition, and statism. We demonstrate how the three aforementioned thinkers modified the original Darwinist thought, enriching it with voluntarism and radical collectivism, all in order for the emerging set of ideas to suit China’s historically determined needs. Overall, our analysis contributes to both the history of International Relations thought in China and the broader debate on the globalisation of IR theory and IR knowledge production.
Objectivist naturalists about life's meaning regard it as implicating no world but the natural one, and yet as deriving from more than just subjective attitudes or interests. Such naturalists must obviously deny prominent religious conceptions of meaning. But must they further deny that it can be found in religious pursuits? In this article, I defend a negative answer by arguing that, contrary to a prima facie plausible consideration in support of a positive answer, and by many objectivist naturalists’ own lights, the meaning of life can be found in pursuits predicated on false belief.
The particle trajectories in irrotational, incompressible and inviscid deep-water surface gravity waves are open, leading to a net drift in the direction of wave propagation commonly referred to as the Stokes drift, which is responsible for catalysing surface wave-induced mixing in the ocean and transporting marine debris. A balance between phase-averaged momentum density, kinetic energy density and vorticity for irrotational, monochromatic and spatially periodic two-dimensional water waves is derived by working directly within the Lagrangian reference frame, which tracks particle trajectories as a function of their labels and time. This balance should be expected as all three of these quantities are conserved following particles in this system. Vorticity in particular is always conserved along particles in two-dimensional inviscid flow, and as such even in its absence it is the value of the vorticity that fundamentally sets the drift, which in the Lagrangian frame is identified as the phase-averaged momentum density of the system. A relationship between the drift and the geometric mean water level of particles is found at the surface, which highlights connections between the geometry and dynamics. Finally, an example of an initially quiescent fluid driven by a wavelike pressure disturbance is considered, showing how the net momentum and energy from the surface pressure disturbance transfer to the wave field, and recognizing the source of the mean Lagrangian drift as the net momentum required to generate an irrotational surface wave by any conservative force.
People with bipolar disorder (BD) often show inaccurate subjective ratings of their objective cognitive function. However, it is unclear what information individuals use to formulate their subjective ratings. This study evaluated whether people with BD are likely using information about their crystallized cognitive abilities (which involve an accumulated store of verbal knowledge and skills and are typically preserved in BD) or their fluid cognitive abilities (which involve the capacity for new learning and information processing in novel situations and are typically impaired in BD) to formulate their subjective cognitive ratings.
Method:
Eighty participants diagnosed with BD and 55 control volunteers were administered cognitive tests assessing crystallized and fluid cognitive abilities. Subjective cognitive functioning was assessed with the Cognitive Failures Questionnaire (CFQ), daily functioning was rated using the Multidimensional Scale of Independent Functioning (MSIF) and the Global Assessment of Functioning Scale (GAF), and quality of life was assessed with the Quality of Life in Bipolar Disorder scale (QoL.BD).
Results:
The BD group exhibited considerably elevated subjective cognitive complaints relative to controls. Among participants with BD, CFQ scores were associated with fluid cognitive abilities including measures of memory and executive function, but not to crystallized abilities. After controlling for objective cognition and depression, higher cognitive complaints predicted poorer psychosocial outcomes.
Conclusions:
Cognitive self-reports in BD may represent a metacognitive difficulty whereby cognitive self-appraisals are distorted by a person’s focus on their cognitive weaknesses rather than strengths. Moreover, negative cognitive self-assessments are associated with poorer daily functioning and diminished quality of life.
We study the influence of a low-frequency harmonic vibration on the formation of the two-dimensional rolling solitary waves in vertically co-flowing two-layer liquid films. The system consists of two adjacent layers of immiscible fluids with the first layer being sandwiched between a vertical solid plate and the second fluid layer. The solid plate oscillates harmonically in the horizontal direction inducing Faraday waves at the liquid–liquid and liquid–air interfaces. We use a reduced hydrodynamic model derived from the Navier–Stokes equations in the long-wave approximation. Linear stability of the base flow in a flat two-layer film is determined semi-analytically using Floquet theory. We consider sub-millimetre-thick films and focus on the competition between the long-wavelength gravity-driven and finite wavelength Faraday instabilities. In the linear regime, the range of unstable wave vectors associated with the gravity-driven instability broadens at low and shrinks at high vibration frequencies. In nonlinear regimes, we find multiple metastable states characterized by solitary-like travelling waves and short pulsating waves. In particular, we find the range of the vibration parameters at which the system is multistable. In this regime, depending on the initial conditions, the long-time dynamics is dominated either by the fully developed solitary-like waves or by the shorter pulsating Faraday waves.
Identification of sugarcane hybrids is difficult when selections are based solely on morphological traits. Our objective was to combine morphological traits and molecular marker analysis to select F1 hybrids from two separate crosses between Djatiroto, a clone of Saccharum spontaneum, and elite sugarcane clones, LCP 85-384 (Cross 97-3144) and CP 62-258 (Cross 97-3146). The maternal inflorescences of Djatiroto were emasculated by submersion in a circulating 45°C hot-water tank for 10 min to minimize self-fertilization. Cross 97-3144 produced 4.7 g of seeds with 338 viable seeds per gram and Cross 97-3146 produced 2.4 g of seeds with 166 viable seeds per gram. After greenhouse germination, 96 progeny from each cross were evaluated in a field plot. Evaluations were conducted on the ratoon crops for stalk diameter (mm), juice Brix (percentage soluble solids), and a randomly amplified polymorphic DNA (RAPD) marker OPA-11-366 that was reproducibly amplified through PCR from the elite clones, but not the maternal S. spontaneum clone. Fifty progeny (52.1%) from Cross 97-3144 and 36 progeny (37.5%) from Cross 97-3146 inherited the RAPD marker. Five putative F1 progeny were selected from each cross, namely US 99-43, US 99-44, US 99-45, US 99-46 and US 99-47 from Cross 97-3144, and US 99-48, US 99-49, US 99-50, US 99-51 and US 99-52 from Cross 97-3146, based on their relatively larger stalk diameter, higher Brix and inheritance of the RAPD marker. The hybrid nature of these selected progeny was verified with sugarcane microsatellite markers. This is the first report of the development of Saccharum hybrids with the cytoplasm of S. spontaneum for breeding purpose through a combination of conventional and molecular breeding approaches. Availability of these F1 hybrids could enhance the genetic diversity of Saccharum germplasm and has enabled sugarcane geneticists and breeders to explore the possible contribution of S. spontaneum cytoplasm in the development of new sugarcane cultivars.
A novel metasurface offering polarization conversion characteristic in five bands is studied and developed in this paper. To provide the anisotropic feature to the structure, a diagonally placed tapered rod is combined with two semicircular stubs. Due to the controlling ability to convert horizontal to vertical polarization and vice versa, and linear to circular polarization (CP), it serves as a multifunctional polarization converter. Simulation results suggest that the proposed polarizer functions as cross polarizer over 4.74−5.12 and 9.12−13.48 GHz. Additionally, it exhibits a distinct type of rotational sense across 4.24−4.68, 5.24−8.64, and 13.72–15.14 GHz in its linear to CP conversion behavior. The axial ratio of the polarizer is well below 3 dB throughout overall CP bands due to the minimum tolerance level in reflection phases with respect to acceptable limits. Moreover, it is noticed that the sense of CP is left-handed in the first band while right-handed in the remaining two bands. Thus, the suggested polarizer has potential to be integrated with antennas for satellite, defense, industry applications for getting the desired type of polarization in the distinguished bands.
In many African countries with hegemonic-party or de facto one-party systems, political leaders have historically exploited ostensibly proper constitutional amendments to undermine constitutionalism, a practice raising questions about the legitimacy, or lack thereof, of such amendments. This article argues that amendment legitimacy is contingent on achieving ‘broad consensus’, a concept endorsed by the African Charter on Democracy, Elections and Governance. Traditional amendment procedures, such as supermajorities and referendums, while crucial, have proven to be imperfect proxies for ensuring such broad consensus. To more effectively safeguard the core constitutional rules of democratic governance, this article contends that political parties must be recognised as key sites of power division and checks and balances. Accordingly, constitutional amendment procedures should require some level of cross-party approval for key amendments, thus preventing individual political groups, regardless of their dominance, from unilaterally altering fundamental rules of the game. This approach would not only enhance the legitimacy of amendments but also serve as a safeguard against contemporary forms of democratic backsliding, where incumbents exploit formal processes to undermine democratic competition. While this process might make constitutional changes more difficult, it would apply only to a narrow set of fundamental aspects of constitutional democracy. Moreover, it does not necessarily conflict with popular self-governance (and its majoritarian expression), but instead calls for an inclusive re-imagining of majoritarianism.
Despite a consensus that the Late Hallstatt ‘princely’ burials heralded the emergence of the earliest complex societies in the central Balkans, there is room for nuance. In this article, the ‘princely’ burial horizon is examined in light of the opposition between group-oriented and individualizing societies, while accepting that burials are as much an ideological statement as a reflection of social structure. On this theoretical basis, the author presents a study of two groups of ‘princely’ burials in North Macedonia and Bosnia in relation to contemporary and later burials, and with reference to settlement size in the Late Hallstatt and Classical–Hellenistic period. His analysis reveals that the inequality in burial assemblages of the Late Hallstatt ‘princely’ burial horizon decreases in the mortuary record of the fifth–fourth century bc, whereas the settlement size in the Classical–Early Hellenistic suggests emerging differentiation.
Clostridioides difficile infection (CDI) research relies upon accurate identification of cases when using electronic health record (EHR) data. We developed and validated a multi-component algorithm to identify hospital-associated CDI using EHR data and determined that the tandem of CDI-specific treatment and laboratory testing has 97% accuracy in identifying HA-CDI cases.