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Some of us recently discussed the problems existing in describing the channels that permit interventricular shunting. We offered suggestions for improvement, particularly when assessing the channel that is found when both arterial trunks arise from the morphologically right ventricle. Our proposals engendered significant debate, with several criticisms appearing in an editorial commentary. The commentator now accepts that not all of the criticisms were justified. In an attempt to seek further consensus, we have now joined with additional colleagues so as to clarify the aspects of our initial work that created potential confusion. Having reviewed the aspects producing the misconceptions, we again provide an overview of the evidence relevant to deficient ventricular septation now provided by knowledge of cardiac development. We show how remodelling of the primary interventricular communication involves the provision of an inlet for the developing right ventricle and an outlet for the developing right ventricle. During this process, the secondary interventricular foramen, which is a subaortic-left ventricular communication when the outflow tract remains supported exclusively by the right ventricle, becomes the outflow tract for the left ventricle, with a subaortic-right ventricular communication then being closed to complete ventricular septation. We show how knowledge of these processes, coupled with an appreciation of the mechanism of formation of the muscular ventricular septum and the separate formation of an embryonic muscular outlet septum, which with normal development becomes the subpulmonary infundibulum, provides the basis for understanding the various phenotypic lesions that permit interventricular shunting in the postnatal heart.
Multicenter clinical trials are essential for evaluating interventions but often face significant challenges in study design, site coordination, participant recruitment, and regulatory compliance. To address these issues, the National Institutes of Health’s National Center for Advancing Translational Sciences established the Trial Innovation Network (TIN). The TIN offers a scientific consultation process, providing access to clinical trial and disease experts who provide input and recommendations throughout the trial’s duration, at no cost to investigators. This approach aims to improve trial design, accelerate implementation, foster interdisciplinary teamwork, and spur innovations that enhance multicenter trial quality and efficiency. The TIN leverages resources of the Clinical and Translational Science Awards (CTSA) program, complementing local capabilities at the investigator’s institution. The Initial Consultation process focuses on the study’s scientific premise, design, site development, recruitment and retention strategies, funding feasibility, and other support areas. As of 6/1/2024, the TIN has provided 431 Initial Consultations to increase efficiency and accelerate trial implementation by delivering customized support and tailored recommendations. Across a range of clinical trials, the TIN has developed standardized, streamlined, and adaptable processes. We describe these processes, provide operational metrics, and include a set of lessons learned for consideration by other trial support and innovation networks.
It remains unclear which individuals with subthreshold depression benefit most from psychological intervention, and what long-term effects this has on symptom deterioration, response and remission.
Aims
To synthesise psychological intervention benefits in adults with subthreshold depression up to 2 years, and explore participant-level effect-modifiers.
Method
Randomised trials comparing psychological intervention with inactive control were identified via systematic search. Authors were contacted to obtain individual participant data (IPD), analysed using Bayesian one-stage meta-analysis. Treatment–covariate interactions were added to examine moderators. Hierarchical-additive models were used to explore treatment benefits conditional on baseline Patient Health Questionnaire 9 (PHQ-9) values.
Results
IPD of 10 671 individuals (50 studies) could be included. We found significant effects on depressive symptom severity up to 12 months (standardised mean-difference [s.m.d.] = −0.48 to −0.27). Effects could not be ascertained up to 24 months (s.m.d. = −0.18). Similar findings emerged for 50% symptom reduction (relative risk = 1.27–2.79), reliable improvement (relative risk = 1.38–3.17), deterioration (relative risk = 0.67–0.54) and close-to-symptom-free status (relative risk = 1.41–2.80). Among participant-level moderators, only initial depression and anxiety severity were highly credible (P > 0.99). Predicted treatment benefits decreased with lower symptom severity but remained minimally important even for very mild symptoms (s.m.d. = −0.33 for PHQ-9 = 5).
Conclusions
Psychological intervention reduces the symptom burden in individuals with subthreshold depression up to 1 year, and protects against symptom deterioration. Benefits up to 2 years are less certain. We find strong support for intervention in subthreshold depression, particularly with PHQ-9 scores ≥ 10. For very mild symptoms, scalable treatments could be an attractive option.
The genus Trypanosoma Gruby, 1843 encompasses unique, flagellate haemoparasites infecting all vertebrate classes globally (excluding Antarctica). While trypanosomes in terrestrial mammals are well-studied due to their medical and veterinary significance, those in fishes remain largely unexplored, with limited data on their life cycles and ecological roles. Furthermore, the phylogenetic relationships of numerous aquatic species are unresolved. This gap is notable in South Africa, a region with high marine fish biodiversity, yet only 2 documented marine trypanosome species, 1 in teleosts and 1 in elasmobranchs are known. Our research aims to bridge this knowledge gap for marine fish trypanosomes along South Africa’s southern coast. Blood samples were collected from 246 fishes spanning 23 species at Chintsa East, Tsitsikamma (Garden Route National Park), Boknes, Kariega River Estuary and Groot River West Estuary from 2020 to 2023. Giemsa-stained blood smears were screened for trypanosomes, which were morphologically characterized. Molecular analyses targeting the 18S rRNA gene region were conducted on blood samples positive for trypanosomes. Combined morphological and molecular evidence identified 4 Trypanosoma species: 1 known species, Trypanosoma nudigobii from the klipfish (Clinus superciliosus) and 3 new species: Trypanosoma sp. A from the prison goby (Caffrogobius gilchristi), Trypanosoma bakana n. sp. from the white steenbras (Lithognathus lithognathus) and Trypanosoma bokkom n. sp. from 5 mullet species [the grooved mullet (Chelon dumerili), South African mullet (Chelon richardsonii), striped mullet (Chelon tricuspidens), fl athead grey mullet (Mugil cephalus) and the freshwater mullet (Pseudomyxus capensis)].
Since the 1950s, the United Nations (UN) has designated days (e.g., World Wetland Day), years (e.g., Year of the Gorilla) and decades (e.g., Decade on Biodiversity) with a commonly stated goal to raise awareness and funding for conservation-oriented initiatives, and these Days, Years and Decades of ‘…’ (hereafter ‘DYDOs’) continue. However, the effectiveness of these initiatives to achieve their stated objectives and to contribute to positive conservation outcomes is unclear. Here we used a binary analysis change model to evaluate the effectiveness of UN conservation-oriented DYDOs observed between 1974 and 2020. We also examined four case studies to understand the different strategies employed to meet specified conservation goals. We found that DYDOs apparently contributed to positive conservation outcomes when they were tied to social media campaigns and/or when they were strategically situated in current events or global discourse. Although the outcomes of DYDOs were varied, those with longer timescales and those that engaged local communities were more likely to be successful. We suggest that DYDO organizers should identify all possible paths of action through the lens of the change model outlined in this paper to strengthen the value and effectiveness of these initiatives in the future. Using this approach could help ensure that resources are used efficiently and effectively, and that initiatives yield positive conservation outcomes that benefit people and nature.
Validated computerized assessments for cognitive functioning are crucial for older individuals and those at risk of cognitive decline. The National Institutes of Health (NIH) Toolbox Cognition Battery (NIHTB-CB) exhibits good construct validity but requires validation in diverse populations and for adults aged 85+. This study uses data from the Assessing Reliable Measurement in Alzheimer’s Disease and cognitive Aging study to explore differences in the factor structure of the NIHTB-CB for adults 85 and older, Black participants versus White participants, and those diagnosed as amnestic Mild Cognitive Impairment (aMCI) vs cognitively normal (CN).
Method:
Subtests from the NACC UDS-3 and NIHTB-CB were administered to 503 community-dwelling Black and White adults ages 55–99 (367 CN; 136 aMCI). Confirmatory factor analyses were used to investigate the original factor structure of NIHTB-CB that forms the basis for NIHTB-CD Index factor scores.
Results:
Factor analyses for all participants and some participant subsets (aMCI, White, 85+) substantiated the two anticipated factors (Fluid and Crystallized). However, while Black aMCI participants had the expected two-factor structure, for Black CN participants, the List Sorting Working Memory and Picture Sequence tests loaded on the Crystallized factor.
Conclusions:
Findings provide psychometric support for the NIHTB-CB. Differences in factor structure between Black CN individuals and Black aMCI individuals suggest potential instability across levels of cognitive impairment. Future research should explore changes in NIHTB-CB across diagnoses in different populations.
Associations between childhood trauma, neurodevelopment, alcohol use disorder (AUD), and posttraumatic stress disorder (PTSD) are understudied during adolescence.
Methods
Using 1652 participants (51.75% female, baseline Mage = 14.3) from the Collaborative Study of the Genetics of Alcoholism, we employed latent growth curve models to (1) examine associations of childhood physical, sexual, and non-assaultive trauma (CPAT, CSAT, and CNAT) with repeated measures of alpha band EEG coherence (EEGc), and (2) assess whether EEGc trajectories were associated with AUD and PTSD symptoms. Sex-specific models accommodated sex differences in trauma exposure, AUD prevalence, and neural development.
Results
In females, CSAT was associated with higher mean levels of EEGc in left frontocentral (LFC, ß = 0.13, p = 0.01) and interhemispheric prefrontal (PFI, ß = 0.16, p < 0.01) regions, but diminished growth in LFC (ß = −0.07, p = 0.02) and PFI (ß = −0.07, p = 0.02). In males, CPAT was associated with lower mean levels (ß = −0.17, p = 0.01) and increased growth (ß = 0.11, p = 0.01) of LFC EEGc. Slope of LFC EEGc was inversely associated with AUD symptoms in females (ß = −1.81, p = 0.01). Intercept of right frontocentral and PFI EEGc were associated with AUD symptoms in males, but in opposite directions. Significant associations between EEGc and PTSD symptoms were also observed in trauma-exposed individuals.
Conclusions
Childhood assaultive trauma is associated with changes in frontal alpha EEGc and subsequent AUD and PTSD symptoms, though patterns differ by sex and trauma type. EEGc findings may inform emerging treatments for PTSD and AUD.
Chapter 8 concludes the book with a study of Ukrainian refugees’ migration to Europe after Russia’s brutal attack on their country in February 2022. It shows that publics and elites across Europe’s political spectrum sustained extraordinary levels of support for the refugees’ inclusion, and deploys the book’s analytical framework to explain why. The EU’s Temporary Protection Directive (TPD) provided Ukrainian citizens with immediate and collective protection and full social rights in EU member states. Public opinion data and political parties’ (including populists’) programs are used to account for positive reception of the refugees, based on their multiple sources of deservingness. Relying on UNHCR, OECD, and other studies of refugees’ reported experiences the chapter assesses progress in their social inclusion as well as deficiencies. It considers welfare nationalist grievances that have arisen in Europe and shows that governments have responded to them as ‘normal politics’ rather than by scapegoating the refugees. The chapter ends by comparing European responses to the MENA and Ukrainian refugee migrations, and externalization agreements to address the continuing problem of migration to Europe from MENA and other third countries.
Chapter 3 focuses on political mobilizers of welfare nationalism, mainly popular attitudes toward welfare deservingness, and agents that mobilized anti-immigrant politics. The chapter elaborates on four types of deservingness criteria for migrants; need or vulnerability, ethnic closeness, contributions to receiving states’ economies and to their national security. It argues that societal norms for outsiders’ deservingness have narrowed in both Europe and Russia. Populist parties, anti-immigrant, and Euroskeptic are shown to be key mobilizers of welfare nationalism, abetted by anti-immigrant mass media. The chapter tracks one major populist party each in Britain, Germany, Italy, Sweden, and Poland, showing how that party gained vote share and national influence by opposing the CEE and MENA migrations. Using party programs and electoral outcomes, it shows how populists reinforced and amplified welfare nationalist grievances in societies, channeling them into electoral success and pressures for exclusionary migration policies. In authoritarian Russia, popular grievances against migrants are shown to be similar to grievances in Europe, but welfare nationalism was mobilized by regional elites, governors, and mayors. The chapter draws on arguments about authoritarian elites’ motivations to respond to popular grievances in order to explain how sub-national leaders used anti-immigrant mobilization for political advantage in Russia’s hybrid regime.
Chapter 4 focuses on labor migration from Central Asia to Russia as the first exclusionary migration cycle. Growing migration after 2000 made Russia one of the world’s major migrant-receiving states. The chapter explains why Putin retained a visa-free regime with the much poorer former Soviet states of CA, allowing millions of their citizens free entry to Russia, where most stayed and worked with undocumented status. As the numbers of the ethnically distant Muslim migrants rose, welfare nationalist grievances emerged in the cities and regions where migrants were concentrated. Citing public opinion surveys, speeches by mayors and governors, election and party platforms, and mass media, the chapter shows how politicians framed and used welfare nationalist discourses to placate citizens and scapegoat migrants for declines in popular welfare. It highlights the role of sub-national officials in mobilizing anti-immigrant politics and channeling pressures for exclusionary policies to Putin. These pressures produced legislative and normative changes that progressively excluded migrant families from social sectors and subjected workers to increasing abuses, including deportations and other forms of exclusion. A sub-set of migrants who contributed to Russia’s national security were treated as more deserving.
Chapter 6 looks at political responses to the MENA migration to Europe from 2011, the most harshly exclusionary case in my study. The migration mixed asylum seekers fleeing wars in Syria, Iraq, and Afghanistan, with labor migrants from other MENA states. The chapter tracks Europe’s progression from initially cautious receptiveness of asylum seekers to policies of exclusion of MENA migrants from the continent. It shows that the growing numbers, migrant “mix,” and terrorist attacks by (mostly non-migrant) Islamic extremists in Europe combined to undermine need-based deservingness, empower populist parties and feed xenophobic media. The chapter focuses on the EU’s turn to militarized securitization of its land and sea borders and ‘externalization of borders’ to Turkey and Libya, policies that ended the migration surge by indiscriminate physical exclusion of migrants and asylum seekers. Case studies show the varied effects of and responses to the migration in the five European cases and in Russia, which received much smaller numbers. Responses to the MENA migration brought international migration to the core of Europe’s politics, entrenched populist parties, and showed the failure of the Geneva Convention asylum system in the 21st century.