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To investigate the symptoms of SARS-CoV-2 infection, their dynamics and their discriminatory power for the disease using longitudinally, prospectively collected information reported at the time of their occurrence. We have analysed data from a large phase 3 clinical UK COVID-19 vaccine trial. The alpha variant was the predominant strain. Participants were assessed for SARS-CoV-2 infection via nasal/throat PCR at recruitment, vaccination appointments, and when symptomatic. Statistical techniques were implemented to infer estimates representative of the UK population, accounting for multiple symptomatic episodes associated with one individual. An optimal diagnostic model for SARS-CoV-2 infection was derived. The 4-month prevalence of SARS-CoV-2 was 2.1%; increasing to 19.4% (16.0%–22.7%) in participants reporting loss of appetite and 31.9% (27.1%–36.8%) in those with anosmia/ageusia. The model identified anosmia and/or ageusia, fever, congestion, and cough to be significantly associated with SARS-CoV-2 infection. Symptoms’ dynamics were vastly different in the two groups; after a slow start peaking later and lasting longer in PCR+ participants, whilst exhibiting a consistent decline in PCR- participants, with, on average, fewer than 3 days of symptoms reported. Anosmia/ageusia peaked late in confirmed SARS-CoV-2 infection (day 12), indicating a low discrimination power for early disease diagnosis.
The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery (WCPCCS) will be held in Washington DC, USA, from Saturday, 26 August, 2023 to Friday, 1 September, 2023, inclusive. The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery will be the largest and most comprehensive scientific meeting dedicated to paediatric and congenital cardiac care ever held. At the time of the writing of this manuscript, The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery has 5,037 registered attendees (and rising) from 117 countries, a truly diverse and international faculty of over 925 individuals from 89 countries, over 2,000 individual abstracts and poster presenters from 101 countries, and a Best Abstract Competition featuring 153 oral abstracts from 34 countries. For information about the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery, please visit the following website: [www.WCPCCS2023.org]. The purpose of this manuscript is to review the activities related to global health and advocacy that will occur at the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery.
Acknowledging the need for urgent change, we wanted to take the opportunity to bring a common voice to the global community and issue the Washington DC WCPCCS Call to Action on Addressing the Global Burden of Pediatric and Congenital Heart Diseases. A copy of this Washington DC WCPCCS Call to Action is provided in the Appendix of this manuscript. This Washington DC WCPCCS Call to Action is an initiative aimed at increasing awareness of the global burden, promoting the development of sustainable care systems, and improving access to high quality and equitable healthcare for children with heart disease as well as adults with congenital heart disease worldwide.
The continent of Australia is home to the dingo (Canis dingo Meyer, 1793), a free-ranging member of the genus Canis. Affectionately known as the ‘king of the Australian bush’, the dingo is the largest extant mammalian predator (other than humans) in Australia. Yet, at an average of 16kg (range 10–25kg) and standing approximately 55cm to the shoulder, they are relatively small for an apex predator. The quintessential dingo is lean with short fur, has erect ears atop a broad head, fluffy tail and is often yellow or ginger in colour with white points on its toes, feet and tail (Smith 2015). However, coat colours and white patches of pure dingoes vary considerably, including sandy white/cream, black and tan, and everything in between (Fig 15.1; Cairns et al 2021a). The dingo is a highly adaptable and resilient predator. It is: present across the entire mainland and occupies all habitat types of Australia; lives in strict social hierarchies and exhibits complex communication; is highly territorial, with a home range that varies greatly depending on the region; and is a generalist and opportunistic hunter that kills and eats a variety of prey, including species much larger than itself (eg kangaroos, Macropus spp.). Due to the threat it may pose to livestock (Fleming et al 2001), the dingo is considered a pest species across much of its range and remains unprotected in many regions and jurisdictions of Australia. Historical and ongoing persecution by humans, primarily in urban and agricultural areas, remains the dingo's biggest threat, and is likely a leading cause of hybridisation events with domestic dogs (Cairns et al 2021b).
The dingo is a naturalised Australian species. The oldest archeological dingo remains have been carbon-dated to be between 3000 and 3500 years old (Balme et al 2018), setting this as a minimum time the species has been present in Australia. Molecular dating efforts indicate that the dingo has been genetically distinct from both dogs and wolves for at least 8000–11,000 years (Cairns and Wilton 2016; Bergstrom et al 2020; Zhang et al 2020). This timing firmly places dingoes as having evolved pre-agriculture and prior to the diversification of other dogs into domestic breeds via intensive artificial selection.
Psychological stress is associated with accelerated cellular aging and increased risk for aging-related diseases, but the underlying molecular mechanisms are unclear.
Methods
We examined the effect of stress on a DNA methylation age predictor that was shown to correlate strongly with chronological age across human tissues (Horvath 2013). Genome-wide DNA methylation was measured in peripheral blood using the 450K Illumina array in three independent cohorts: the Grady Trauma Project/GTP (N=366); a panic disorder case/control sample recruited at the Max Planck Institute of Psychiatry/MPI-P (N=318); and the Conte Center for the Psychobiology of Early-Life Trauma/Conte (N=42). Age acceleration was calculated by subtracting chronological age from age predicted by DNA methylation. Psychiatric symptomatology and stressors were assessed using standard questionnaires.
Results
DNA methylation age strongly correlated with chronological age in all samples (r=0.9, p=2.5x10<sup>-133</sup>). Cumulative lifetime stress but not childhood or current stress predicted age acceleration in GTP (p=0.012) and MPI-P (p=0.021). Moreover, epigenetic age acceleration predicted depression (GTP: p=0.002; Conte: p=0.014) and panic disorder (p=0.007). In secondary analyses, we examined the effect of lifetime stress on individual CpGs of the DNA methylation age predictor. After correcting for multiple comparisons, we identified in both GTP and MPI-P a stress-regulated CpG near MCAM, a gene implicated in aging-related diseases, including cardiovascular disease and cancers.
Conclusions
Cumulative lifetime stress, but not childhood or current stress, and psychiatric phenotypes are associated with accelerated epigenetic aging. Our findings may explain the accelerated cellular aging and increased disease risk associated with chronic stress and psychiatric disorders.
This paper summarises developments in understanding sea level change during the Quaternary in Scotland since the publication of the Quaternary of Scotland Geological Conservation Review volume in 1993. We present a review of progress in methodology, particularly in the study of sediments in isolation basins and estuaries as well as in techniques in the field and laboratory, which have together disclosed greater detail in the record of relative sea level (RSL) change than was available in 1993. However, progress in determining the record of RSL change varies in different areas. Studies of sediments and stratigraphy offshore on the continental shelf have increased greatly, but the record of RSL change there remains patchy. Studies onshore have resulted in improvements in the knowledge of rock shorelines, including the processes by which they are formed, but much remains to be understood. Studies of Late Devensian and Holocene RSLs around present coasts have improved knowledge of both the extent and age range of the evidence. The record of RSL change on the W and NW coasts has disclosed a much longer dated RSL record than was available before 1993, possibly with evidence of Meltwater Pulse 1A, while studies in estuaries on the E and SW coasts have disclosed widespread and consistent fluctuations in Holocene RSLs. Evidence for the meltwater pulse associated with the Early Holocene discharge of Lakes Agassiz–Ojibway in N America has been found on both E and W coasts. The effects of the impact of storminess, in particular in cliff-top storm deposits, have been widely identified. Further information on the Holocene Storegga Slide tsunami has enabled a better understanding of the event, but evidence for other tsunami events on Scottish coasts remains uncertain. Methodological developments have led to new reconstructions of RSL change for the last 2000 years, utilising state-of-the-art GIA models and alongside coastal biostratigraphy to determine trends to compare with modern tide gauge and documentary evidence. Developments in GIA modelling have provided valuable information on patterns of land uplift during and following deglaciation. The studies undertaken raise a number of research questions which will require addressing in future work.
Fontan survivors have depressed cardiac index that worsens over time. Serum biomarker measurement is minimally invasive, rapid, widely available, and may be useful for serial monitoring. The purpose of this study was to identify biomarkers that correlate with lower cardiac index in Fontan patients.
Methods and results
This study was a multi-centre case series assessing the correlations between biomarkers and cardiac magnetic resonance-derived cardiac index in Fontan patients ⩾6 years of age with biochemical and haematopoietic biomarkers obtained ±12 months from cardiac magnetic resonance. Medical history and biomarker values were obtained by chart review. Spearman’s Rank correlation assessed associations between biomarker z-scores and cardiac index. Biomarkers with significant correlations had receiver operating characteristic curves and area under the curve estimated. In total, 97 cardiac magnetic resonances in 87 patients met inclusion criteria: median age at cardiac magnetic resonance was 15 (6–33) years. Significant correlations were found between cardiac index and total alkaline phosphatase (−0.26, p=0.04), estimated creatinine clearance (0.26, p=0.02), and mean corpuscular volume (−0.32, p<0.01). Area under the curve for the three individual biomarkers was 0.63–0.69. Area under the curve for the three-biomarker panel was 0.75. Comparison of cardiac index above and below the receiver operating characteristic curve-identified cut-off points revealed significant differences for each biomarker (p<0.01) and for the composite panel [median cardiac index for higher-risk group=2.17 L/minute/m2 versus lower-risk group=2.96 L/minute/m2, (p<0.01)].
Conclusions
Higher total alkaline phosphatase and mean corpuscular volume as well as lower estimated creatinine clearance identify Fontan patients with lower cardiac index. Using biomarkers to monitor haemodynamics and organ-specific effects warrants prospective investigation.
Infection surveillance definitions for long-term care facilities (ie, the McGeer Criteria) have not been updated since 1991. An expert consensus panel modified these definitions on the basis of a structured review of the literature. Significant changes were made to the criteria defining urinary tract and respiratory tract infections. New definitions were added for norovirus gastroenteritis and Clostridum difficile infections.
We present photometry and spectroscopy of the peculiar Type II supernova SN 2010jp, also named PTF10aaxi. The light curve exhibits a linear decline with a relatively low peak absolute magnitude of only −15.9 (unfiltered), and a low radioactive decay luminosity at late times that suggests a low synthesized nickel mass of about 0.003 M⊙ or less. Spectra of SN 2010jp display an unprecedented triple-peaked Hα line profile, showing: (1) a narrow central component that suggests shock interaction with a dense circumstellar medium (CSM); (2) high-velocity blue and red emission features centered at −12,600 and +15,400 km s−1; and (3) very broad wings extending from −22,000 to +25,000 km s−1. We propose that this line profile indicates a bipolar jet-driven explosion, with the central component produced by normal SN ejecta and CSM interaction at mid and low latitudes, while the high-velocity bumps and broad line wings arise in a nonrelativistic bipolar jet. Jet-driven SNe II are predicted for collapsars resulting from a wide range of initial masses above 25 M⊙, especially at the sub-solar metallicity consistent with the SN host environment. It also seems consistent with the apparently low 56Ni mass that may accompany black hole formation. We speculate that the jet survives to produce observable signatures because the star's H envelope was very low mass, having been mostly stripped away by the previous eruptive mass loss.
Cortical spreading depression (CSD) produces propagating waves of transient neuronal hyperexcitability followed by depression. CSD is initiated by K+ release following neuronal firing or electrical, mechanical or chemical stimuli. A triphasic (30–50 s) cortical potential transient accompanies localized transmembrane redistributions of K+, glutamate, Ca2+, Na+, Cl− and H+. Accumulated K+ in the restricted interstitial space can cause both further neuronal depolarisation and inward movement of K+ into astrocytes that buffers this increased extracellular K+ concentration ([K+])o. However, astrocyte interconnections may then propagate the CSD wave by K+ liberation through an opening of remote K+ channels by volume, Ca2+ or N-methyl-D-aspartate receptor activation. Changes in cerebral blood volume and in apparent water diffusion co-efficient (ADC) accompanying CSD were first studied using magnetic resonance imaging (MRI) in whole lissencephalic brains. Diffusion-weighted echoplanar imaging in gyrencephalic brains went on to demonstrate CSD features that paralleled classical migraine aura. The ADC activity persisted minutes/hours post KCl stimulus. Pixelwise analyses distinguished single primary events and multiple, spatially restricted, slower propagating, secondary events whose detailed features varied with the nature of the originating stimulus. These ADC changes varied reciprocally with T2*-weighted (i.e. referring to spin-spin relaxation times) waveforms reflecting local blood flow. There followed prolonged decreases in cerebral blood flow culminating in late cerebrovascular changes blocked by the antimigraine agent sumatriptan. CSD phenomena have possible translational significance for human migraine aura and other cerebral pathologies such as the peri-infarct depolarisation events that follow ischaemia and brain injury.