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The Fontan Outcomes Network was created to improve outcomes for children and adults with single ventricle CHD living with Fontan circulation. The network mission is to optimise longevity and quality of life by improving physical health, neurodevelopmental outcomes, resilience, and emotional health for these individuals and their families. This manuscript describes the systematic design of this new learning health network, including the initial steps in development of a national, lifespan registry, and pilot testing of data collection forms at 10 congenital heart centres.
Clozapine is uniquely effective in treatment-resistant psychosis but remains underutilised, partly owing to psychotic symptoms leading to non-adherence to oral medication. An intramuscular formulation is available in the UK but outcomes remain unexplored.
This was a retrospective clinical effectiveness study of intramuscular clozapine prescription for treatment initiation and maintenance in treatment-resistant psychosis over a 3-year period.
Successful initiation of oral clozapine after intramuscular prescription was the primary outcome. Secondary outcomes included all-cause clozapine discontinuation 2 years following initiation, and 1 year after discharge. Discontinuation rates were compared with a cohort prescribed only oral clozapine. Propensity scores were used to address confounding by indication.
Among 39 patients prescribed intramuscular clozapine, 19 received at least one injection, whereas 20 accepted oral clozapine when given an enforced choice between the two. Thirty-six (92%) patients successfully initiated oral clozapine after intramuscular prescription; three never transitioned to oral. Eight discontinued oral clozapine during the 2-year follow-up, compared with 83 out of 162 in the comparator group (discontinuation rates of 24% and 50%, respectively). Discontinuation rates at 1-year post-discharge were 21%, compared with 44% in the comparison group. Intramuscular clozapine prescription was associated with a non-significantly lower hazard of discontinuation 2 years after initiation (hazard ratio 0.39, 95% CI 0.14–1.06) and 1 year after discharge (hazard ratio 0.37, 95% CI 0.11–1.24). The only reported adverse event specific to the intramuscular formulation was injection site pain and swelling.
Intramuscular clozapine prescription allowed transition to oral maintenance in an initially non-adherent cohort. Discontinuation rates were similar to patients only prescribed oral clozapine and comparable to existing literature.
The lack of radiation knowledge among the general public continues to be a challenge for building communities prepared for radiological emergencies. This study applied a multi-criteria decision analysis (MCDA) to the results of an expert survey to identify priority risk reduction messages and challenges to increasing community radiological emergency preparedness.
Professionals with expertise in radiological emergency preparedness, state/local health and emergency management officials, and journalists/journalism academics were surveyed following a purposive sampling methodology. An MCDA was used to weight criteria of importance in a radiological emergency, and the weighted criteria were applied to topics such as sheltering-in-place, decontamination, and use of potassium iodide. Results were reviewed by respondent group and in aggregate.
Sheltering-in-place and evacuation plans were identified as the most important risk reduction measures to communicate to the public. Possible communication challenges during a radiological emergency included access to accurate information; low levels of public trust; public knowledge about radiation; and communications infrastructure failures.
Future assessments for community readiness for a radiological emergency should include questions about sheltering-in-place and evacuation plans to inform risk communication.
Large carnivores have extensive spatial requirements, with ranges that often span geopolitical borders. Consequently, management of transboundary populations is subject to several political jurisdictions, often with heterogeneity in conservation challenges. In continental Asia there are four threatened leopard subspecies with transboundary populations spanning 23 countries: the Persian Panthera pardus saxicolor, Indochinese P. pardus delacouri, Arabian P. pardus nimr and Amur P. pardus orientalis leopards. We reviewed the status of these subspecies and examined the challenges to, and opportunities for, their conservation. The Amur and Indochinese leopards have the majority (58–100%) of their remaining range in borderlands, and the Persian and Arabian leopards have 23–26% of their remaining ranges in borderlands. Overall, in 18 of 23 countries the majority of the remaining leopard range is in borderlands, and thus in most countries conservation of these subspecies is dependent on transboundary collaboration. However, we found only two transboundary initiatives for Asian leopards. Overall, we highlighted three key transboundary landscapes in regions that are of high importance for the survival of these subspecies. Recent listing of the leopard in the Bonn Convention on the Conservation of Migratory Species of Wild Animals is important, but more international collaboration is needed to conserve these subspecies. We provide a spatial framework with which range countries and international agencies could establish transboundary cooperation for conserving threatened leopards in Asia.
Anxiety is an understandable response to perceived threat or experienced stress, and is usually fleeting and feels controllable: it represents an ‘alarm’, facilitating physical and psychological responses to perceived danger. Anxiety symptoms are mostly mild and transient, but many people experience severe and persistent symptoms that cause distress and impair everyday function. An anxiety disorder can be diagnosed when distressing and impairing anxiety exceeds specified severity thresholds and persists beyond minimum duration requirements, providing symptoms are not explicable by another condition. Insomnia is a common disorder in which sleep is reduced in amount or quality so that daytime well-being and functioning is impaired.
Intensified cover cropping practices are increasingly viewed as an herbicide resistance management tool but clear distinction between reactive and proactive resistance management performance targets is needed. We evaluated two proactive performance targets for integrating cover cropping tactics, including (1) facilitation of reduced herbicide inputs, and (2) reduced herbicide selection pressure. We conducted corn (Zea mays L.) and soybean [Glycine max (L.) Merr] field experiments in Pennsylvania and Delaware using synthetic weed seedbanks of horseweed [Conyza canadensis (L.) Cronquist] and smooth pigweed (Amaranthus hybridus L.) to assess winter- and summer- annual population dynamics, respectively. The effect of alternative cover crops was evaluated across a range of herbicide inputs. Cover crop biomass production ranged from 2,000 to 8,500 kg ha-1 in corn and 3,000 to 5,500 kg ha-1 in soybean. Experimental results demonstrated that herbicide-based tactics were the primary drivers of total weed biomass production with cover cropping tactics providing an additive weed suppression benefit. Substitution of cover crops for PRE or POST herbicide programs did not reduce total weed control levels or cash crop yields but did result in lower net returns due to higher input costs. Cover cropping tactics significantly reduced C. canadensis populations in three of four cover crop treatments and decreased the number of large rosettes (> 7.6 cm diameter) at the time of pre-plant herbicide exposure. Substitution of cover crops for PRE herbicides resulted in increased selection pressure on POST herbicides, but reduced the number of large individuals (> 10 cm) at POST applications. Collectively, our findings suggest that cover crops can reduce the intensity of selection pressure on POST herbicides but the magnitude of the effect varies based on weed life-history traits. Additional work is needed to describe proactive resistance management concepts and performance targets for integrating cover crops so producers can apply these concepts in site-specific, within-field management practices.
Major depression (MD) is often characterised as a categorical disorder; however, observational studies comparing sub-threshold and clinical depression suggest MD is continuous. Many of these studies do not explore the full continuum and are yet to consider genetics as a risk factor. This study sought to understand if polygenic risk for MD could provide insight into the continuous nature of depression.
Factor analysis on symptom-level data from the UK Biobank (N = 148 957) was used to derive continuous depression phenotypes which were tested for association with polygenic risk scores (PRS) for a categorical definition of MD (N = 119 692).
Confirmatory factor analysis showed a five-factor hierarchical model, incorporating 15 of the original 18 items taken from the PHQ-9, GAD-7 and subjective well-being questionnaires, produced good fit to the observed covariance matrix (CFI = 0.992, TLI = 0.99, RMSEA = 0.038, SRMR = 0.031). MD PRS associated with each factor score (standardised β range: 0.057–0.064) and the association remained when the sample was stratified into case- and control-only subsets. The case-only subset had an increased association compared to controls for all factors, shown via a significant interaction between lifetime MD diagnosis and MD PRS (p value range: 2.23 × 10−3–3.94 × 10−7).
An association between MD PRS and a continuous phenotype of depressive symptoms in case- and control-only subsets provides support against a purely categorical phenotype; indicating further insights into MD can be obtained when this within-group variation is considered. The stronger association within cases suggests this variation may be of particular importance.
Wild sheep and many primitive domesticated breeds have two coats: coarse hairs covering shorter, finer fibres. Both are shed annually. Exploitation of wool for apparel in the Bronze Age encouraged breeding for denser fleeces and continuously growing white fibres. The Merino is regarded as the culmination of this process. Archaeological discoveries, ancient images and parchment records portray this as an evolutionary progression, spanning millennia. However, examination of the fleeces from feral, two-coated and woolled sheep has revealed a ready facility of the follicle population to change from shedding to continuous growth and to revert from domesticated to primitive states. Modifications to coat structure, colour and composition have occurred in timeframes and to sheep population sizes that exclude the likelihood of variations arising from mutations and natural selection. The features are characteristic of the domestication phenotype: an assemblage of developmental, physiological, skeletal and hormonal modifications common to a wide variety of species under human control. The phenotypic similarities appeared to result from an accumulation of cryptic genetic changes early during vertebrate evolution. Because they did not affect fitness in the wild, the mutations were protected from adverse selection, becoming apparent only after exposure to a domestic environment. The neural crest, a transient embryonic cell population unique to vertebrates, has been implicated in the manifestations of the domesticated phenotype. This hypothesis is discussed with reference to the development of the wool follicle population and the particular roles of Notch pathway genes, culminating in the specific cell interactions that typify follicle initiation.
Assessment of unique and potentially significant fossils may be considerably compromised by surrounding matrix. This paper assesses a fossil barnacle group from the mid to late Eocene of Seymour Island, off the Antarctic Peninsula, that potentially has very significant phylogenetic importance. It discusses why the specimen could be significant, and describes and applies as a proof of concept an advanced imaging technique, using X-ray Computed Tomography (CT), that was effectively employed to confirm systematic taxonomy with virtual 3-D sections through the specimen. In this case, the Antarctic barnacle's complex internal plate morphologies were resolved by advanced 3-D imaging, such that a taxonomic attribution could be made to either the Archaeobalanidae or Austrobalanidae, excluding the initial assessment of Coronulidae, which would have otherwise been allusive.
Accurate near-field measurements for either deterministic or stochastic electromagnetic fields characterization require a relevant process that removes the influence of the probes, transmission lines, and measurement circuits. The main part of the experimental work presented here is related to a calibration procedure of a test setup consisting of a microstrip test structure and a scanning loop probe. The calibration characteristic, obtained by comparing measured and simulated results, is then used to convert the measured voltage into the magnetic field across and along the microstrip line at the specific height above it. By performing the measurements and simulations of the same test structure with the loop probe in the presence of an additional scanning probe, the influence of the additional probe to the measured output is thoroughly investigated and relevant corrections are given. These corrections can be important when two-point correlation measurement is required, especially in scanning points when two probes are mutually close.
In response to the rapid spread of novel coronavirus disease 2019 (COVID-19), health-care systems should establish procedures for early recognition and management of suspected or confirmed cases. We describe the various steps taken for the development, implementation, and dissemination of the interdisciplinary COVID-19 protocol at Jackson Health System (JHS), a complex tertiary academic health system in Miami, Florida. Recognizing the dynamic nature of COVID-19, the protocol addresses the potential investigational treatment options and considerations for special populations. The protocol also includes infection prevention and control measures and routine care for suspected or proven COVID-19 patients.
The extent of intertidal flats in the Yellow Sea region has declined significantly in the past few decades, resulting in severe population declines in several waterbird species. The Yellow Sea region holds the primary stopover sites for many shorebirds during their migration to and from northern breeding grounds. However, the functional roles of these sites in shorebirds’ stopover ecology remain poorly understood. Through field surveys between July and November 2015, we investigated the stopover and moult schedules of migratory shorebirds along the southern Jiangsu coast, eastern China during their southbound migration, with a focus on the ‘Critically Endangered’ Spoon-billed Sandpiper Calidris pygmaea and ‘Endangered’ Nordmann’s Greenshank Tringa guttifer. Long-term count data indicate that both species regularly occur in globally important number in southern Jiangsu coast, constituting 16.67–49.34% and 64.0–80.67% of their global population estimates respectively, and it is highly likely that most adults undergo their primary moult during this southbound migration stopover. Our results show that Spoon-billed Sandpiper and Nordmann’s Greenshank staged for an extended period of time (66 and 84 days, respectively) to complete their primary moult. On average, Spoon-billed Sandpipers and Nordmann’s Greenshanks started moulting primary feathers on 8 August ± 4.52 and 27 July ± 1.56 days respectively, and their moult durations were 72.58 ± 9.08 and 65.09 ± 2.40 days. In addition, some individuals of several other shorebird species including the ‘Endangered’ Great Knot Calidris tenuirostris, ‘Near Threatened’ Bar-tailed Godwit Limosa lapponica, ‘Near Threatened’ Eurasian Curlew Numenius arquata and Greater Sand Plover Charadrius leschenaultii also underwent primary moult. Our work highlights the importance of the southern Jiangsu region as the primary moulting ground for these species, reinforcing that conservation of shorebird habitat including both intertidal flats and supratidal roosting sites in this region is critical to safeguard the future of some highly threatened shorebird species.
Estimation of intravascular volume status by clinical examination and static measurements such as central venous pressure and pulmonary capillary wedge pressure do not predict fluid responsiveness. Current evidence indicates that dynamic monitoring of arterial pressure and derived indices are the most sensitive and specific means of determining fluid responsiveness, especially in mechanically ventilated patients. Several monitors that automate and embellish this approach, a few of which are noninvasive, are now commercially available and they are gradually being incorporated into intensive and perioperative care practice. This chapter reviews the physiologic underpinnings of how and why the arterial pressure waveform can be used to determine fluid responsiveness and gives an overview of the devices incorporating these principles.
Although trauma-focused cognitive behavior therapy (TF-CBT) is the frontline treatment for post-traumatic stress disorder (PTSD), one-third of patients are treatment non-responders. To identify neural markers of treatment response to TF-CBT when participants are reappraising aversive material.
This study assessed PTSD patients (n = 37) prior to TF-CBT during functional magnetic brain resonance imaging (fMRI) when they reappraised or watched traumatic images. Patients then underwent nine sessions of TF-CBT, and were then assessed for symptom severity on the Clinician-Administered PTSD Scale. FMRI responses for cognitive reappraisal and emotional reactivity contrasts of traumatic images were correlated with the reduction of PTSD severity from pretreatment to post-treatment.
Symptom improvement was associated with decreased activation of the left amygdala during reappraisal, but increased activation of bilateral amygdala and hippocampus during emotional reactivity prior to treatment. Lower connectivity of the left amygdala to the subgenual anterior cingulate cortex, pregenual anterior cingulate cortex, and right insula, and that between the left hippocampus and right amygdala were also associated with symptom improvement.
These findings provide evidence that optimal treatment response to TF-CBT involves the capacity to engage emotional networks during emotional processing, and also to reduce the engagement of these networks when down-regulating emotions.
This report documents the last pteraspids, (armored, jawless members of the Heterostraci), which are otherwise only known from the Early Devonian of the Old Red Sandstone Continent. Tuberculate pteraspid heterostracans are described from the Middle Devonian beds of two formations in western North America. The late Givetian Yahatinda Formation of Alberta and British Columbia consists of channels cut into lower Paleozoic rocks and represents deposition in marine to littoral environments. Clavulaspis finis (Elliott et al., 2000a) new combination is redescribed from additional material from the Yahatinda Formation and reassigned to the new genus Clavulaspis because the original genus name is invalid. The Eifelian Spring Mountain beds of Idaho consist of a large channel that represents a clastic-dominated estuarine environment. It contains Scutellaspis wilsoni new genus new species, and the previously described species from the Spring Mountain beds is redescribed and reassigned to Ecphymaspis new genus, which was prompted by new material and a review of the validity of the original genus name. Phylogenetic analysis shows that these three new taxa form part of the derived clade Protaspididae.