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Pulmonary hypertension is a complex and progressive condition that is either idiopathic or heritable, or associated with one or multiple health conditions, with or without congenital or acquired cardiovascular disease. Recent developments have tremendously increased the armamentarium of diagnostic and therapeutic approaches in children and young adults with pulmonary hypertension that is still associated with a high morbidity and mortality. These modalities include non-invasive imaging, pharmacotherapy, interventional and surgical procedures, and supportive measures. The optimal, tailored diagnostic and therapeutic strategies for pulmonary hypertension in the young are rapidly evolving but still face enormous challenges: Healthcare providers need to take the patient’s age, development, disease state, and family concerns into account when initiating advanced diagnostics and treatment. Therefore, there is a need for guidance on core and advanced medical training in paediatric pulmonary hypertension. The Association for European Paediatric and Congenital Cardiology working group “pulmonary hypertension, heart failure and transplantation” has produced this document as an expert consensus statement; however, all recommendations must be considered and applied in the context of the local and national infrastructure and legal regulations.
Compound-specific radiocarbon (14C) dating often requires working with small samples of < 100 µg carbon (µgC). This makes the radiocarbon dates of biomarker compounds very sensitive to biases caused by extraneous carbon of unknown composition, a procedural blank, which is introduced to the samples during the steps necessary to prepare a sample for radiocarbon analysis by accelerator mass spectrometry (i.e., isolating single compounds from a heterogeneous mixture, combustion, gas purification and graphitization). Reporting accurate radiocarbon dates thus requires a correction for the procedural blank. We present our approach to assess the fraction modern carbon (F14C) and the mass of the procedural blanks introduced during the preparation procedures of lipid biomarkers (i.e. n-alkanoic acids) and lignin phenols. We isolated differently sized aliquots (6–151 µgC) of n-alkanoic acids and lignin phenols obtained from standard materials with known F14C values. Each compound class was extracted from two standard materials (one fossil, one modern) and purified using the same procedures as for natural samples of unknown F14C. There is an inverse linear relationship between the measured F14C values of the processed aliquots and their mass, which suggests constant contamination during processing of individual samples. We use Bayesian methods to fit linear regression lines between F14C and 1/mass for the fossil and modern standards. The intersection points of these lines are used to infer F14Cblank and mblank and their associated uncertainties. We estimate 4.88 ± 0.69 μgC of procedural blank with F14C of 0.714 ± 0.077 for n-alkanoic acids, and 0.90 ± 0.23 μgC of procedural blank with F14C of 0.813 ± 0.155 for lignin phenols. These F14Cblank and mblank can be used to correct AMS results of lipid and lignin samples by isotopic mass balance. This method may serve as a standardized procedure for blank assessment in small-scale radiocarbon analysis.
Cognitive impairment is a core feature of major depressive disorder (MDD). Cognitive remediation may improve cognition in MDD, yet so far, the underlying neural mechanisms are unclear. This study investigated changes in intrinsic neural activity in MDD after a cognitive remediation trial.
In a longitudinal design, 20 patients with MDD and pronounced cognitive deficits and 18 healthy controls (HC) were examined using resting-state functional magnetic resonance imaging. MDD patients received structured cognitive remediation therapy (CRT) over 5 weeks. The whole-brain fractional amplitude of low-frequency fluctuations was computed before the first and after the last training session. Univariate methods were used to address regionally-specific effects, and a multivariate data analysis strategy was employed to investigate functional network strength (FNS).
MDD patients significantly improved in cognitive function after CRT. Baseline comparisons revealed increased right caudate activity and reduced activity in the left frontal cortex, parietal lobule, insula, and precuneus in MDD compared to HC. In patients, reduced FNS was found in a bilateral prefrontal system at baseline (p < 0.05, uncorrected). In MDD, intrinsic neural activity increased in right inferior frontal gyrus after CRT (p < 0.05, small volume corrected). Left inferior parietal lobule, left insula, left precuneus, and right caudate activity showed associations with cognitive improvement (p < 0.05, uncorrected). Prefrontal network strength increased in patients after CRT, but this increase was not associated with improved cognitive performance.
Our findings support the role of intrinsic neural activity of the prefrontal cortex as a possible mediator of cognitive improvement following CRT in MDD.
Broad-spectrum antibiotic de-escalation before and after implementation of a 72-hour antibiotic time-out alert within the electronic medical record was analyzed. De-escalation occurred significantly more often after the implementation of the alert (55.0% vs 35.1%; 95% confidence interval, −0.3491 to −0.0488; P < .01).
To explore the use of fluorescence lifetime imaging microscopy in thyroid tissues, and to investigate how different thyroid lesions affect fluorescence lifetime.
Fluorescence lifetime measurements were taken of fresh frozen thyroid surgical specimens stained with fluorescein isothiocyanate tagged anti-thyroglobulin monoclonal antibodies.
The mean fluorescence lifetime measurements in 12 patients – 3 with multinodular goitre, 4 with follicular adenoma, 4 with papillary thyroid carcinoma and 1 with follicular carcinoma – were 3.16 ns (range, 2.66–3.52 ns), 3.75 ns (range, 2.99–4.57 ns), 2.97 ns (range, 2.57–3.21 ns) and 3.61 ns, respectively. The fluorescence lifetime of follicular adenoma patients was higher than that of papillary thyroid carcinoma patients by 26 per cent (p = 0.058). The fluorescence lifetime in the follicular carcinoma patient was similar to the follicular adenoma group, but higher than in the papillary thyroid carcinoma group by 22 per cent (p = 0.01).
Fluorescence lifetime measurements varied in different thyroid pathologies, possibly because of tissue-scale structural influences.
Background: Biallelic variants in POLR1C are associated with POLR3-related leukodystrophy (POLR3-HLD), or 4H leukodystrophy (Hypomyelination, Hypodontia, Hypogonadotropic Hypogonadism), and Treacher Collins syndrome (TCS). The clinical spectrum of POLR3-HLD caused by variants in this gene has not been described. Methods: A cross-sectional observational study involving 25 centers worldwide was conducted between 2016 and 2018. The clinical, radiologic and molecular features of 23 unreported and previously reported cases of POLR3-HLD caused by POLR1C variants were reviewed. Results: Most participants presented between birth and age 6 years with motor difficulties. Neurological deterioration was seen during childhood, suggesting a more severe phenotype than previously described. The dental, ocular and endocrine features often seen in POLR3-HLD were not invariably present. Five patients (22%) had a combination of hypomyelinating leukodystrophy and abnormal craniofacial development, including one individual with clear TCS features. Several cases did not exhibit all the typical radiologic characteristics of POLR3-HLD. A total of 29 different pathogenic variants in POLR1C were identified, including 13 new disease-causing variants. Conclusions: Based on the largest cohort of patients to date, these results suggest novel characteristics of POLR1C-related disorder, with a spectrum of clinical involvement characterized by hypomyelinating leukodystrophy with or without abnormal craniofacial development reminiscent of TCS.
A procedure using tube excited energy dispersive x-ray fluorescence analysis with interelement corrections has been developed for multielement analysis of major and trace elements and ash content of coal, coke, and fly ash. The procedure uses pressed pellets and an exponential correction for interelement effects. The average deviations ranged from about 0.0003% for V at an average concentration of about .003% to 0.1% for S at an average concentration of 4%. About 25 elements were measured and 100 second minimum detectable concentrations ranged from about one part per million for elements near arsenic to about one tenth of one percent for sodium.
Objectives: To adequately monitor the course of cognitive functioning in persons with moderate to severe dementia, relevant cognitive tests for the advanced dementia stages are needed. We examined the ability of a test developed for the advanced dementia stages, the Severe Impairment Battery Short version (SIB-S), to measure cognitive change over time. Second, we examined type of memory impairment measured with the SIB-S in different dementia stages. Methods: Participants were institutionalized persons with moderate to severe dementia (N = 217). The SIB-S was administered at 6-month intervals during a 2-year period. Dementia severity at baseline was classified according to Global Deterioration Scale criteria. We used mixed models to evaluate the course of SIB-S total and domain scores, and whether dementia stage at baseline affected these courses. Results: SIB-S total scores declined significantly over time, and the course of decline differed significantly between dementia stages at baseline. Persons with moderately severe dementia declined faster in mean SIB-S total scores than persons with moderate or severe dementia. Between persons with moderate and moderately severe dementia, there was only a difference in the rate of decline of semantic items, but not episodic and non-semantic items. Conclusions: Although modest floor and slight ceiling effects were noted in severe and milder cases, respectively, the SIB-S proved to be one of few available adequate measures of cognitive change in institutionalized persons with moderate to severe dementia. (JINS, 2019, 25, 204–214)
AFM-based nanoelectrical modes have numerous
applications in fields ranging from semiconductors
to biology. The data produced have traditionally
been in the form of a 2D map, generated in contact
mode, with a single electrical data point per
XY location. Electrical ramps
or spectra would be generated at a few, carefully
selected locations. This article discusses a new
approach to nanoelectrical imaging that creates an
electrical data cube and a correlated nanomechanical
data cube while operating at normal imaging speeds.
This approach avoids contact mode imaging, thus
extending electrical measurements to soft and
fragile samples and improving measurement
consistency. Moreover, this is a general approach
that is applicable to most nanoelectrical modes and
Childhood obesity is a common concern across global cities and threatens sustainable urban development. Initiatives to improve nutrition and encourage physical exercise are promising but are yet to exert significant influence on prevention. Childhood obesity in London is associated with distinct ethnic and socio-economic patterns. Ethnic inequalities in health-related behaviour endure, underpinned by inequalities in employment, housing, access to welfare services, and discrimination. Addressing these growing concerns requires a clearer understanding of the socio-cultural, environmental and economic contexts of urban living that promote obesity. We explore opportunities for prevention using asset based-approaches to nutritional health and well-being, with a particular focus on adolescents from diverse ethnic backgrounds living in London. We focus on the important role that community engagement and multi-sectoral partnership play in improving the nutritional outcomes of London's children. London's children and adolescents grow up in the rich cultural mix of a global city where local streets are characterised by diversity in ethnicities, languages, religions, foods, and customs, creating complex and fluid identities. Growing up with such everyday diversity we argue can enhance the quality of life for London's children and strengthen their social capital. The Determinants of young Adult Social well-being and Health longitudinal study of about 6500 of London's young people demonstrated the positive impact of cultural diversity. Born to parents from over a hundred countries and exposed to multi-lingual households and religious practices, they demonstrated strong psychological resilience and sense of pride from cultural straddling, despite material disadvantage and discrimination. Supporting the potential contribution of such socio-cultural assets is in keeping with the values of social justice and equitable and sustainable development. Our work signals the importance of community engagement and multisectoral partnerships, involving, for example, schools and faith-based organisations, to improve the nutrition of London's children.
Externalizing disorders are known to be partly heritable, but the biological pathways linking genetic risk to the manifestation of these costly behaviors remain under investigation. This study sought to identify neural phenotypes associated with genomic vulnerability for externalizing disorders.
One-hundred fifty-five White, non-Hispanic veterans were genotyped using a genome-wide array and underwent resting-state functional magnetic resonance imaging. Genetic susceptibility was assessed using an independently developed polygenic score (PS) for externalizing, and functional neural networks were identified using graph theory based network analysis. Tasks of inhibitory control and psychiatric diagnosis (alcohol/substance use disorders) were used to measure externalizing phenotypes.
A polygenic externalizing disorder score (PS) predicted connectivity in a brain circuit (10 nodes, nine links) centered on left amygdala that included several cortical [bilateral inferior frontal gyrus (IFG) pars triangularis, left rostral anterior cingulate cortex (rACC)] and subcortical (bilateral amygdala, hippocampus, and striatum) regions. Directional analyses revealed that bilateral amygdala influenced left prefrontal cortex (IFG) in participants scoring higher on the externalizing PS, whereas the opposite direction of influence was observed for those scoring lower on the PS. Polygenic variation was also associated with higher Participation Coefficient for bilateral amygdala and left rACC, suggesting that genes related to externalizing modulated the extent to which these nodes functioned as communication hubs.
Findings suggest that externalizing polygenic risk is associated with disrupted connectivity in a neural network implicated in emotion regulation, impulse control, and reinforcement learning. Results provide evidence that this network represents a genetically associated neurobiological vulnerability for externalizing disorders.
The impact of natural disasters and climate change on archaeological resources has garnered much recent attention, with impacts of sea level rise and coastal flooding being the two most often cited issues. However, damage caused by flooding of interior areas and waterways has received less consideration. In this article, we present a case study of a collaborative emergency response to a significant weather event and the ensuing impacts on archaeological resources. Our project, located in Middle Tennessee, documented severe erosion and subsequent anthropogenic disturbances to ancient Native American sites following massive flooding of the Cumberland River in 2010. While striving to mitigate this damage via systematic collection of imperiled archaeological samples, we were also able to strengthen partnerships among professional archaeologists working in different arenas (academia, state and federal agencies) and the avocational archaeological community. As these types of weather-related events become more common, published case studies of response efforts will be crucial in archaeological site management, planning, and disaster response.
Traumatic stressors during childhood and adolescence are associated with psychopathology, mostly studied in the context of post-traumatic stress disorder (PTSD) and depression. We investigated broader associations of traumatic stress exposure with psychopathology and cognition in a youth community sample.
The Philadelphia Neurodevelopmental Cohort (N = 9498) is an investigation of clinical and neurobehavioral phenotypes in a diverse (56% Caucasian, 33% African American, 11% other) US youth community population (aged 8–21). Participants were ascertained through children's hospital pediatric (not psychiatric) healthcare network in 2009–2011. Structured psychiatric evaluation included screening for lifetime exposure to traumatic stressors, and a neurocognitive battery was administered.
Exposure rate to traumatic stressful events was high (none, N = 5204; one, N = 2182; two, N = 1092; three or more, N = 830). Higher stress load was associated with increased psychopathology across all clinical domains evaluated: mood/anxiety (standardized β = .378); psychosis spectrum (β = .360); externalizing behaviors (β = .311); and fear (β = .256) (controlling for covariates, all p < 0.001). Associations remained significant controlling for lifetime PTSD and depression. Exposure to high-stress load was robustly associated with suicidal ideation and cannabis use (odds ratio compared with non-exposed 5.3 and 3.2, respectively, both p < 0.001). Among youths who experienced traumatic stress (N = 4104), history of assaultive trauma was associated with greater psychopathology and, in males, vulnerability to psychosis and externalizing symptoms. Stress load was negatively associated with performance on executive functioning, complex reasoning, and social cognition.
Traumatic stress exposure in community non-psychiatric help-seeking youth is substantial, and is associated with more severe psychopathology and neurocognitive deficits across domains, beyond PTSD and depression.
From a 45ks Chandra observation of V42G Oph we have obtained high-resolution X-ray spectra at moderate signal-to-noise, and a, good quality, uninterrupted lightcurve. The spectra are reasonably fit with a cooling flow model, similar to EX Hya and U Gem. Our analysis of the Chandra and additional X-ray/optical lightcurves reveals a persistent modulation at 4.2 hr from 1988 to 2003, likely the white dwarf spin period indicating an intermediate polar nature for V426 Oph.