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Innominate vein redirection to the pulmonary venous atrium has been used in single ventricle patients in order to relieve lymphatic complications resulting from systemic venous hypertension. This has been achieved both surgically, known as the Hraska procedure and via transcatheter approach, known as the Rome procedure. Determining the pathway from the innominate vein to the pulmonary venous atrium is challenging with important intra- and extra-cardiac structures close-by. We present two cases; one surgical and one transcatheter approach, where 3D-printed cardiac models were used to assist in the pre-procedural planning of this relatively novel and challenging strategy.
The extent to which legislators pursue their privately held preferences in office has important implications for representative democracy and is exceedingly difficult to measure. Many models of legislative decision-making tacitly assume that members are willing and able to carry out the wishes of their constituents so as to maximize their reelection prospects and, in so doing, relegate their personal preferences. This project explores this assumption by examining the role that members’ place of birth plays in shaping legislative behavior, apart from other politically relevant factors like partisanship. We find that birthplace exerts an independent influence on members’ voting behavior. Using a variety of geographic measures, we find that members who are born in close proximity to one another tend to exhibit similar patterns in roll call voting, even when accounting for partisanship, constituency attributes, and a variety of other determinants of voting. We also demonstrate in a secondary analysis that the agricultural composition of members’ birthplace influences their support for agricultural protection. Our findings suggest that members’ personal history shapes the representational relationship they have with their constituents.
Maladaptive daydreaming is a distinct syndrome in which the main symptom is excessive vivid fantasising that causes clinically significant distress and functional impairment in academic, vocational and social domains. Unlike normal daydreaming, maladaptive daydreaming is persistent, compulsive and detrimental to one’s life. It involves detachment from reality in favour of intense emotional engagement with alternative realities and often includes specific features such as psychomotor stereotypies (e.g. pacing in circles, jumping or shaking one’s hands), mouthing dialogues, facial gestures or enacting fantasy events. Comorbidity is common, but existing disorders do not account for the phenomenology of the symptoms. Whereas non-specific therapy is ineffective, targeted treatment seems promising. Thus, we propose that maladaptive daydreaming be considered a formal syndrome in psychiatric taxonomies, positioned within the dissociative disorders category. Maladaptive daydreaming satisfactorily meets criteria for conceptualisation as a psychiatric syndrome, including reliable discrimination from other disorders and solid interrater agreement. It involves significant dissociative aspects, such as disconnection from perception, behaviour and sense of self, and has some commonalities with but is not subsumed under existing dissociative disorders. Formal recognition of maladaptive daydreaming as a dissociative disorder will encourage awareness of a growing problem and spur theoretical, research and clinical developments.
A series of webinars covering widespread knowledge on paediatric cardiology and cardiac surgery topics was initiated by Association for European Paediatric and Congenital Cardiology, serving towards preparation for the Association for European Paediatric and Congenital Cardiology certification in paediatric and congenital cardiology. This study investigated the impact of webinars as educational tools for junior paediatric cardiologists in the post-COVID-19 pandemic era.
Materials and methods:
A cross-sectional survey design study using an online survey as a tool for the assessment of trainees. An open and closed-ended SurveyMonkey questionnaire was used to document the learners’ opinions on webinars. Results were reported using descriptive statistical analyses.
Results:
Twenty-seven Association for European Paediatric and Congenital Cardiology junior members participated in the online survey from twelve different countries. Most of the participants were trainees in paediatric cardiology (56%), and the remainder were junior consultants in paediatric cardiology. Approximately 70% found no difficulties in participating in the webinars. The webinars were appreciated by participants, who found the webinars interactive and highly educational with contents highly applicable to everyday clinical practice. Significant heterogeneity emerged in training programmes across Europe and worldwide in terms of programme duration, number of fellows, teaching approach, and assessments. Training opportunities such as courses, grants, and more webinars were suggested as tools to support continuous learning by the Association for European Paediatric and Congenital Cardiology.
Conclusion:
The Association for European Paediatric and Congenital Cardiology webinar series has confirmed the crucial role of online-based learning resources in the new generation of junior paediatric cardiologists. Association for European Paediatric and Congenital Cardiology webinars and the examination in paediatric cardiology may help standardise training across Europe, promoting the highest standards in patient care.
Although atypical antipsychotics have lowered the prevalence and severity of extrapyramidal symptoms (EPS), they still contribute to the overall side-effect burden of approved antipsychotics. Drugs with novel mechanisms without D2 dopamine receptor blocking activity have shown promise in treating schizophrenia without the side effects of currently available treatments. KarXT (xanomeline–trospium chloride) represents a possible alternative that targets muscarinic receptors. KarXT demonstrated efficacy compared with placebo in 3 out of 3 short-term acute studies and has not been associated with many of the side effects of D2 dopamine receptor antagonists. Here, we further characterize EPS rates with KarXT in these trials.
Methods
EMERGENT-1 (NCT03697252), EMERGENT-2 (NCT04659161), and EMERGENT-3 (NCT04738123) were 5-week, randomized, double-blind, placebo-controlled, inpatient trials in people with schizophrenia experiencing acute psychosis. Data from the safety populations, defined as all participants who received ³1 dose of trial medication, were pooled. For this analysis, we used a broader definition of EPS-related adverse events (AEs) to encompass any new onset of dystonia, dyskinesia, akathisia, or extrapyramidal disorder reported any time after the first dose of medication. Additionally, EPS were assessed by examining change from baseline to week 5 on the Simpson-Angus Scale (SAS), Barnes Akathisia Rating Scale (BARS), and Abnormal Involuntary Movement Scale (AIMS).
Results
A total of 683 participants (KarXT, n=340; placebo, n=343) were included in the analyses. The rate of treatment-emergent AEs (TEAEs) associated with EPS was 3.2% in the KarXT group vs 0.9% in the placebo group. The most commonly reported TEAE was akathisia (KarXT, 2.4%; placebo 0.9%); half of possible akathisia cases in the KarXT group (4/8 TEAEs) were from a single US site, considered by the investigator to be unrelated to trial drug, and resolved without treatment. Overall rates of akathisia TEAEs deemed related to trial drug were low (KarXT, 0.6%; placebo 0.3%). Dystonia, dyskinesia, and extrapyramidal disorder TEAEs were reported by only a single subject each (0.3%) in the KarXT arm. All reported TEAEs were mild to moderate in severity. KarXT was associated with no clinically meaningful mean±SD changes from baseline to week 5 on the SAS (-0.1±0.6), BARS (-0.1±0.9), or AIMS (0.0±0.7).
Conclusions
The incidence of EPS-related TEAEs with KarXT was low in comparison to those observed in similar trials of antipsychotics (D2 dopamine receptor antagonists), although head-to-head studies have not been completed. Moreover, KarXT was not associated with increased scores on EPS scales (SAS, BARS, AIMS) across 5 weeks of treatment. These results, combined with the robust efficacy of KarXT in trials to date, suggest that KarXT’s novel mechanism of action may provide therapeutic benefit in the absence of EPS frequently associated with currently available antipsychotics.
The delivery of paediatric cardiac care across the world occurs in settings with significant variability in available resources. Irrespective of the resources locally available, we must always strive to improve the quality of care we provide to our patients and simultaneously deliver such care in the most efficient and cost-effective manner. The development of cardiac networks is used widely to achieve these aims.
Methods:
This paper reports three talks presented during the 56th meeting of the Association for European Paediatric and Congenital Cardiology held in Dublin in April 2023.
Results:
The three talks describe how centres of congenital cardiac excellence can be developed in low-income countries, middle-income countries, and well-resourced environments, and also reports how centres across different countries can come together to collaborate and deliver high-quality care. It is a fact that barriers to creating effective networks may arise from competition that may exist among programmes in unregulated and especially privatised health care environments. Nevertheless, reflecting on the creation of networks has important implications because collaboration between different centres can facilitate the maintenance of sustainable programmes of paediatric and congenital cardiac care.
Conclusion:
This article examines the delivery of paediatric and congenital cardiac care in resource limited environments, well-resourced environments, and within collaborative networks, with the hope that the lessons learned from these examples can be helpful to other institutions across the world. It is important to emphasise that irrespective of the differences in resources across different continents, the critical principles underlying provision of excellent care in different environments remain the same.
Robert Clewis focuses on a number of different themes in Kant’s precritical and critical aesthetics in The Origins of Kant’s Aesthetics. Clewis carefully documents where Kant’s views on these themes are the same, where they are different, and why; yet his approach might give readers the impression that Kant lacks a unified conception of aesthetics. I show, on the contrary, that the method and sources Clewis employs also reveal the frameworks within which Kant addresses the themes that Clewis discusses in Origins; the consistencies in Kant’s precritical and critical conceptions of aesthetics; and the changes in his conception of aesthetics that we find in the third Critique.
Warfarin is used as anticoagulation for children for a wide range of cardiac indications but carries the disadvantage of requiring international normalised ratio monitoring and dose adjustment. Management of warfarin therapy is challenging due to its narrow therapeutic window and is further complicated in children by dietary changes, frequent illnesses, and developing systems of metabolism and haemostasis.
A retrospective review was performed of patients’ medical records to assess the indication for warfarin use, percentage of international normalised ratio values in target range (%ITR), and frequency of phlebotomy.
Twenty-six patients were identified. The most common indication for warfarin use was in patients post-total cavo-pulmonary connection (n = 19, 73%). We demonstrated a variability in duration of warfarin therapy following total cavo-pulmonary connection (median of 11.1 months). Nineteen (73%) patients had used the CoaguChek machine for home measurement of international normalised ratio. The median frequency of phlebotomy for all indications was once every 10 days, and the median %ITR was 55.4 % (29.7–86.4%). Of note, the percentage under target range in the patients with mechanical mitral (n = 2) and aortic valves (n = 1) was found to be 23% and 33%, respectively.
These data demonstrate a high frequency of international normalised ratio values outside of the target range as seen in previous studies of warfarin in children. This necessitates frequent phlebotomy and dose changes, which can have a significant effect on the quality of life of these patients and their families highlighting the need to focus on quality improvement in the area of anticoagulation in paediatric cardiac patients.
Globally, there is seasonal variation in tuberculosis (TB) incidence, yet the biological and behavioural or social factors driving TB seasonality differ across countries. Understanding season-specific risk factors that may be specific to the UK could help shape future decision-making for TB control. We conducted a time-series analysis using data from 152,424 UK TB notifications between 2000 and 2018. Notifications were aggregated by year, month, and socio-demographic covariates, and negative binomial regression models fitted to the aggregate data. For each covariate, we calculated the size of the seasonal effect as the incidence risk ratio (IRR) for the peak versus the trough months within the year and the timing of the peak, whilst accounting for the overall trend. There was strong evidence for seasonality (p < 0.0001) with an IRR of 1.27 (95% CI 1.23–1.30). The peak was estimated to occur at the beginning of May. Significant differences in seasonal amplitude were identified across age groups, ethnicity, site of disease, latitude and, for those born abroad, time since entry to the UK. The smaller amplitude in older adults, and greater amplitude among South Asians and people who recently entered the UK may indicate the role of latent TB reactivation and vitamin D deficiency in driving seasonality.
Many paediatric studies report that patients must be established on aspirin therapy for a minimum of 5 days to achieve adequate response. This is not always practical especially in critical settings. Prospective identification of patients that are unresponsive to aspirin sooner could potentially prevent thrombotic events.
Aims:
The aim of this study was to investigate prospectively if the first dose of aspirin is effective in decreasing platelet aggregation, and thromboxane formation and if this can be measured after 2 hours in paediatric cardiology patients. A secondary aim was to identify a cut-off for a novel marker of aspirin responsiveness the maximum amplitude with arachidonic acid, which could potentially dramatically reduce the blood volume required. Third, we aimed to prospectively identify potentially non-responsive patients by spiking a sample of their blood ex vivo with aspirin.
Results:
The majority (92.3%) of patients were responsive, when measured 2 hours post first dose of aspirin. Non-response or inadequate response (7.7%) can also be identified at 2 hours after taking the first dose of aspirin. Additionally, we have shown a novel way to reduce blood sample volume requirements by measurement of the maximum amplitude with arachidonic acid as a marker of response, particularly for monitoring.
Conclusions:
These findings of rapid efficacy in the majority of patients offer assurance in a sound, practical way to attending clinicians, patients, and families.
With the rise of online references, podcasts, webinars, self-test tools, and social media, it is worthwhile to understand whether textbooks continue to provide value in medical education, and to assess the capacity they serve during fellowship training.
Methods:
A prospective mixed-methods study based on surveys that were disseminated to seven paediatric cardiology fellowship programmes around the world. Participants were asked to read an assigned chapter of Anderson’s Pediatric Cardiology 4th Edition textbook, followed by the completion of the survey. Open-ended questions included theming and grouping responses as appropriate.
Results:
The survey was completed by 36 participants. When asked about the content, organisation, and utility of the chapter, responses were generally positive, at greater than 89%. The chapters, overall, were rated relatively easy to read, scoring at 6.91, with standard deviations plus or minus 1.72, on a scale from 1 to 10, with higher values meaning better results. When asked to rank their preferences in where they obtain educational content, textbooks were ranked the second highest, with in-person teaching ranking first. Several themes were identified including the limitations of the use of textbook use, their value, and ways to enhance learning from their reading. There was also a near-unanimous desire for more time to self-learn and read during fellowship.
Conclusions:
Textbooks are still highly valued by trainees. Many opportunities exist, nonetheless, to improve how they can be organised to deliver information optimally. Future efforts should look towards making them more accessible, and to include more resources for asynchronous learning.
Sperlingite, (H2O)K(Mn2+Fe3+)(Al2Ti)(PO4)4[O(OH)][(H2O)9(OH)]⋅4H2O, is a new monoclinic member of the paulkerrite group, from the Hagendorf-Süd pegmatite, Oberpfalz, Bavaria, Germany. It was found in corrosion pits of altered zwieselite, in association with columbite, hopeite, leucophosphite, mitridatite, scholzite, orange–brown zincoberaunite sprays and tiny green crystals of zincolibethenite. Sperlingite forms colourless prisms with pyramidal terminations, which are predominantly only 5 to 20 μm in size, rarely to 60 μm and frequently are multiply intergrown and are overgrown with smaller crystals. The crystals are flattened on {010} and slightly elongated along [100] with forms {010}, {001} and {111}. Twinning occurs by rotation about c. The calculated density is 2.40 g⋅cm–3. Optically, sperlingite crystals are biaxial (+), α = 1.600(est), β = 1.615(5), γ = 1.635(5) (white light) and 2V (calc.) = 82.7°. The optical orientation is X = b, Y = c and Z = a. Neither dispersion nor pleochroism were observed. The empirical formula from electron microprobe analyses and structure refinement is A1[(H2O)0.96K0.04]Σ1.00A2(K0.52□0.48)Σ1.00M1(Mn2+0.60Mg0.33Zn0.29Fe3+0.77)Σ1.99M2+M3(Al1.05Ti4+1.33Fe3+0.62)Σ3.00(PO4)4X[F0.19(OH)0.94O0.87]Σ2.00[(H2O)9.23(OH)0.77]Σ10.00⋅3.96H2O. Sperlingite has monoclinic symmetry with space group P21/c and unit-cell parameters a = 10.428(2) Å, b = 20.281(4) Å, c = 12.223(2) Å, β = 90.10(3)°, V = 2585.0(8) Å3 and Z = 4. The crystal structure was refined using synchrotron single-crystal data to wRobs = 0.058 for 5608 reflections with I > 3σ(I). Sperlingite is the first paulkerrite-group mineral to have co-dominant divalent and trivalent cations at the M1 sites; All other reported members have Mn2+ or Mg dominant at M1. Local charge balance for Fe3+ at M1 is achieved by H2O → OH– at H2O coordinated to M1.
The first stage of lateritic weathering of pyroxenes in the Niquelandia area, Brazil, leads either to Fe-rich products or to a phyllosilicate clay. In relatively unfractured parent rock the phyllosilicate clay contains Ni-rich smectites, the atomic ratio of Ni: octahedral cations ranging from 0.3 to 0.5. These smectites were studied by polarized light microscopy, X-ray powder diffraction (XRD), transmission electron microscopy, and electron microprobe, and infrared, optical absorption, Mössbauer, and extended X-ray absorption fine-structure (EXAFS) spectroscopy. The chemical composition of the smectite is constant on the optical microscope scale even to the smallest analyzed particles (3000 A in diameter and about 75 Å thick). From XRD data the mineral is principally a swelling, trioctahedral smectite; however, some kerolite-pimelite-like layers are present, and a weak 06,33 reflection indicates the presence of a small amount of a dioctahedral phase. Mössbauer results show that all Fe cations are Fe3+ in octahedral sites. The structural formula of the smectite is: (Ca0.01K0.05)(Al0.17Fe0.5Mg0.48Ni1.47Cr0.02)(Si3.92Al0.08)O10(OH)2
The results obtained from all the above methods suggest that in the smectites Ni, and, perhaps, a small amount of Mg are clustered in pimelite-like domains (or layers), whereas Fe and some Al are clustered in nontronite-like domains (or layers). Most selected-area electron diffraction patterns exhibit continuous or punctuated (hk) rings, indicating that particles contain several stacked layers. The patterns of some thin particles, however, suggest dioctahedral layers having trans-octahedral vacancies, such as in the Garfield, Washington, nontronite. Thus, the Ni-Fe-Mg-smectite, which seemingly is homogeneous, actually consists of mixed trioctahedral and dioctahedral layers or domains.
The enthalpy of freezing of methyl salicylate sorbed by four commercial montmorillonite clays was used to estimate the absorption/adsorption capacity of the clay. Differential thermal analysis was therefore employed to give a quantitative estimate of the sorption capacity of the clay for methyl salicylate. The absorption capacity of the clay depended on the state of hydration and ranged from 30.4% for an 8% water content to 9.7% for a montmorillonite containing 24% water.
The brain can be represented as a network, with nodes as brain regions and edges as region-to-region connections. Nodes with the most connections (hubs) are central to efficient brain function. Current findings on structural differences in Major Depressive Disorder (MDD) identified using network approaches remain inconsistent, potentially due to small sample sizes. It is still uncertain at what level of the connectome hierarchy differences may exist, and whether they are concentrated in hubs, disrupting fundamental brain connectivity.
Methods
We utilized two large cohorts, UK Biobank (UKB, N = 5104) and Generation Scotland (GS, N = 725), to investigate MDD case–control differences in brain network properties. Network analysis was done across four hierarchical levels: (1) global, (2) tier (nodes grouped into four tiers based on degree) and rich club (between-hub connections), (3) nodal, and (4) connection.
Results
In UKB, reductions in network efficiency were observed in MDD cases globally (d = −0.076, pFDR = 0.033), across all tiers (d = −0.069 to −0.079, pFDR = 0.020), and in hubs (d = −0.080 to −0.113, pFDR = 0.013–0.035). No differences in rich club organization and region-to-region connections were identified. The effect sizes and direction for these associations were generally consistent in GS, albeit not significant in our lower-N replication sample.
Conclusion
Our results suggest that the brain's fundamental rich club structure is similar in MDD cases and controls, but subtle topological differences exist across the brain. Consistent with recent large-scale neuroimaging findings, our findings offer a connectomic perspective on a similar scale and support the idea that minimal differences exist between MDD cases and controls.