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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.
Understanding the factors contributing to optimal cognitive function throughout the aging process is essential to better understand successful cognitive aging. Processing speed is an age sensitive cognitive domain that usually declines early in the aging process; however, this cognitive skill is essential for other cognitive tasks and everyday functioning. Evaluating brain network interactions in cognitively healthy older adults can help us understand how brain characteristics variations affect cognitive functioning. Functional connections among groups of brain areas give insight into the brain’s organization, and the cognitive effects of aging may relate to this large-scale organization. To follow-up on our prior work, we sought to replicate our findings regarding network segregation’s relationship with processing speed. In order to address possible influences of node location or network membership we replicated the analysis across 4 different node sets.
Participants and Methods:
Data were acquired as part of a multi-center study of 85+ cognitively normal individuals, the McKnight Brain Aging Registry (MBAR). For this analysis, we included 146 community-dwelling, cognitively unimpaired older adults, ages 85-99, who had undergone structural and BOLD resting state MRI scans and a battery of neuropsychological tests. Exploratory factor analysis identified the processing speed factor of interest. We preprocessed BOLD scans using fmriprep, Ciftify, and XCPEngine algorithms. We used 4 different sets of connectivity-based parcellation: 1)MBAR data used to define nodes and Power (2011) atlas used to determine node network membership, 2) Younger adults data used to define nodes (Chan 2014) and Power (2011) atlas used to determine node network membership, 3) Older adults data from a different study (Han 2018) used to define nodes and Power (2011) atlas used to determine node network membership, and 4) MBAR data used to define nodes and MBAR data based community detection used to determine node network membership.
Segregation (balance of within-network and between-network connections) was measured within the association system and three wellcharacterized networks: Default Mode Network (DMN), Cingulo-Opercular Network (CON), and Fronto-Parietal Network (FPN). Correlation between processing speed and association system and networks was performed for all 4 node sets.
Results:
We replicated prior work and found the segregation of both the cortical association system, the segregation of FPN and DMN had a consistent relationship with processing speed across all node sets (association system range of correlations: r=.294 to .342, FPN: r=.254 to .272, DMN: r=.263 to .273). Additionally, compared to parcellations created with older adults, the parcellation created based on younger individuals showed attenuated and less robust findings as those with older adults (association system r=.263, FPN r=.255, DMN r=.263).
Conclusions:
This study shows that network segregation of the oldest-old brain is closely linked with processing speed and this relationship is replicable across different node sets created with varied datasets. This work adds to the growing body of knowledge about age-related dedifferentiation by demonstrating replicability and consistency of the finding that as essential cognitive skill, processing speed, is associated with differentiated functional networks even in very old individuals experiencing successful cognitive aging.
The introduction of transoral robotic surgery into routine management of patients is complex. It involves organisational, logistical and clinical challenges. This study presents our experience of implementing such a programme and provides a blueprint for other centres willing to establish similar services.
Methods
Implementation of the robotic surgery programme focused on several key domains: training, logistics, governance, multidisciplinary team awareness, pre-operative imaging, anaesthesia, post-operative care, finance, patient selection and consent. Programme outcomes were evaluated by assessing operative outcomes of the first 117 procedures performed.
Results
The success of the transoral robotic surgery programme has been possible because of the scrupulous planning phase before the first procedure, and the time invested on team awareness and training.
Conclusion
Implementation of a new transoral robotic surgery service has led to: the development of a dedicated transoral robotic surgery patient care protocol, the performance of progressively more complex procedures, the inclusion of transoral robotic surgery training and the establishment of several research projects.
Complete BVRCIC light curves of V1187 Her were obtained in May 2017 at the Dark Sky Observatory in North Carolina with the 0.81-m reflector of Appalachian State University. Earlier, spectra were taken at the Dominion Astrophysical Observatory with the 1.8-m telescope. The spectral type was found to be F8±1 V (6250 K), so the binary is of solar-type. V1187 Her was previously identified as a low amplitude (V < 0.2 mag), short period, overcontact eclipsing binary (EW) with a period of 0.310726 d. Strikingly, despite its low amplitude, the early light curves show total eclipses (eclipse duration ≍31.5 minutes), which is a characteristic of an extreme mass ratio binary. A period study covering 11 years reveals a continuous period decrease dP/dt=–4.7×10–9 d yr–1. The multi-band Wilson-Devinney light curve solution gives a fill-out of 79% and a mass ratio of only 0.0440±0.0001. There is a cool spot region on the secondary component, which is 400 K hotter than the primary. The inclination is only 66.85±0.05 despite the system’s total eclipses.
Introduction: Run to Quit is a national community-based program that combines smoking cessation support with physical activity through learn to run group-based curriculum, self-help and smoking cessation materials. The program is currently in a three-year scaling up phase.
Aims: The aim of the current study is to explore participant experiences of the Run to Quit program after its first year, and identify potential areas of improvement for future iterations of the program.
Methods: Participants (n = 55) were interviewed over the phone at the end of the 10-week program. Participant interviews were recorded and transcribed. A thematic analysis was conducted.
Results/Findings: Participants were satisfied with the program. Strengths of the program were the group aspect, supervised participation and the running. Weaknesses were seen as the variability in walking and running abilities and inadequate engagement by the Smokers Helpline. Many people who successfully quit smoking reported using additional quit aids. Non-completers of the program gave mostly logistical and personal reasons for dropout.
Conclusions: Overall, Run to Quit was well received by participants. Multiple health behaviour interventions at a scalable level appear feasible. Based on participant feedback, key recommendations to improve the program in the future include greater tailoring to walking or running preference, and increasing engagement with the Smokers Helpline.
An enormous effort is underway worldwide to attempt to detect gravitational waves. If successful, this will open a new frontier in astronomy. An essential portion of this effort is being carried out in Australia by the Australian Consortium for Interferometric Gravitational Astronomy (ACIGA), with research teams working at the Australia National University, University of Western Australia, and University of Adelaide involving scientists and students representing many more institutions and nations. ACIGA is developing ultrastable high-power continuous-wave lasers for the next generation interferometric gravity wave detectors; researching the problems associated with high optical power in resonant cavities; opening frontiers in advanced interferometry configurations, quantum optics, and signal extraction; and is the world's leader in high-performance vibration isolation and suspension design. ACIGA has also been active in theoretical research and modelling of potential astronomical gravitational wave sources, and in developing data analysis detection algorithms. ACIGA has opened a research facility north of Perth, Western Australia, which will be the culmination of these efforts. This paper briefly reviews ACIGA's research activities and the prospects for gravitational wave astronomy in the southern hemisphere.
Larger portion sizes (PS) may be inciting over-eating and contributing to obesity rates. Currently, there is a paucity of data on the effectiveness of serving size (SS) guidance. The aims of the present review are to evaluate SS guidance; the understanding, usability and acceptability of such guidance, its impact on consumers and potential barriers to its uptake. A sample of worldwide SS guidance schemes (n 87) were identified using targeted and untargeted searches, overall these were found to communicate various inconsistent and often conflicting messages about PS selection. The available data suggest that consumers have difficulty in understanding terms such as ‘portion size’ and ‘serving size’, as these tend to be used interchangeably. In addition, discrepancies between recommended SS and those present on food labels add to the confusion. Consumers generally understand and visualise SS best when expressed in terms of household measures rather than actual weights. Only a limited number of studies have examined the direct impact of SS guidance on consumer behaviour with equivocal results. Although consumers recognise that guidance on selecting SS would be helpful, they are often unwilling to act on such guidance. The challenge of achieving consumer adherence to SS guidance is formidable due to several barriers including chronic exposure to larger PS, distorted consumption norms and perceptions, the habit of ‘cleaning one's plate’ and language barriers for ethnic minorities. In conclusion, the impact of SS guidance on consumers merits further investigation to ensure that future guidance resonates with consumers by being more understandable, usable and acceptable.
Solar-type variability is enhanced in short period close binaries with increased dynamo driven activity. This activity is studied in our analysis of recent light curves taken of the newly discovered eclipsing binaries GSC 2764 1417 (And), GSC 3355 0394 (Per) and GSC 2537 0775 (CVn).
During the past decade, the number known shallow-amplitude, yet totally eclipsing, extreme-mass-ratio binaries has increased from one (AW UMa, which is now in doubt) to about a dozen. Statistics are accumulating that will tell us the nature of these once rare systems. These individual interacting field binaries are believed to be the progenitors of FK Comae-type fast-rotating subgiants, which are similar to the cluster stars called ‘variable blue stragglers.’ We review our recent observations and new analyses of the individual systems, V409 Hya, GSC 1283 0053 Ori, GSC 2537 520 CVn, using the 2007 Wilson Code and summarize results from our previous observations (V802 Aql, V902 Sgr) and those from the literature (e.g., CK Boo, GR Vir, HV Aqr, UY UMa, EM Pis, CU Tau, TV Mus) to disclose a preliminary picture of the character of this interesting class of binary stars.
The effect of diet v. statins on LDL particle size as a risk factor for CVD has not been examined. We compared, in the same subjects, the impact of a dietary portfolio of cholesterol-lowering foods and a statin on LDL size electrophoretic characteristics. Thirty-four hyperlipidaemic subjects completed three 1-month treatments as outpatients in random order: a very-low saturated fat diet (control); the same diet with 20 mg lovastatin; a dietary portfolio high in plant sterols (1 g/4200 kJ), soya proteins (21·4 g/4200 kJ), soluble fibres (9·8 g/4200 kJ) and almonds (14 g/4200 kJ). LDL electrophoretic characteristics were measured by non-denaturing polyacrylamide gradient gel electrophoresis of fasting plasma at 0, 2 and 4 weeks of each treatment. The reductions in plasma LDL-cholesterol levels with the dietary portfolio and with statins were comparable and were largely attributable to reductions in the estimated concentration of cholesterol within the smallest subclass of LDL (portfolio − 0·69 (se 0·10) mmol/l, statin − 0·99 (se 0·10) mmol/l). These were significantly greater (P < 0·01) than changes observed after the control diet ( − 0·17 (se 0·08) mmol/l). Finally, baseline C-reactive protein levels were a significant predictor of the LDL size responsiveness to the dietary portfolio but not to the other treatments. The dietary portfolio, like the statin treatment, had only minor effects on several features of the LDL size phenotype, but the pronounced reduction in cholesterol levels within the small LDL fraction may provide additional cardiovascular benefit over the traditional low-fat diet of National Cholesterol Education Program Step II.
We have found photometric indications that Interacting Eclipsing Binaries of early to mid F spectral type (and possibly A) have strong magnetic activity which would arise from convective atmospheres. Light curve solutions and periodicity studies revealing spots, magnetic breaking and magnetic cycles are presented in XZ CMi, V965 Cyg and V963 Cyg.
The understanding of radiation-induced grain boundary segregation (RIS) has considerably improved over the past decade. New models have been introduced and much effort has been devoted to obtaining comprehensive information on segregation from the literature. Analytical techniques have also improved so that chemical analysis of layers 1 nm thick is almost routine. This invited paper will review the major methods used currently for RIS prediction: namely, Rate Theory, Inverse Kirkendall, and Solute Drag approaches. A summary is made of the available data on phosphorus RIS in reactor pressure vessel (RPV) steels. This will be discussed in the light of the predictions of the various models in an effort to show which models are the most reliable and easy to use for forecasting P segregation behaviour in steels. A consequence of RIS in RPV steels is a radiation induced shift in the ductile to brittle transition temperature (DBTT). It will be shown how it is possible to relate radiation-induced P segregation levels to DBTT shift. Examples of this exercise will be given for RPV steels and for ferritic steels being considered for first wall fusion applications. Cr RIS in high alloy stainless steels and associated irradiation-assisted stress corrosion cracking (IASCC) will be briefly discussed.