The climate crisis, climate anxiety and children’s rights: a psychological perspective on human health and security

The climate crisis affects children’s well-being and threatens future generations’ enjoyment of the right to the highest standard of health and security. This paper discusses a submission by the PSI Special Interest Group in Human Rights and Psychology to the UN Committee on the Rights of the Child. As health profession stakeholders we highlight how environmental degradation and children’s awareness of climate change present an important linkage to children’s mental health. We provide a psychological health account of climate anxiety and its effects on children, and a psychological perspective on the UN Convention on the Rights of the Child regarding health and participation. We detail how interventions mindful of children’s educational and participatory capacity offer the potential to moderate effects of climate anxiety. We discuss limitations of the term ‘climate anxiety’ for describing the experience of children from the Global South, preferring a narrative of physical and mental health parity

Nurturing voices: psychologists’ role in amplifying children and young people's participation rights in decision making

Children have a fundamental right to participate in decision making across settings, including physical (Quaye, Coyne, Soderback, 2019) and mental health, family law proceedings (Tisdall, 2016), and educational and local area planning processes (Usher, 2023). However, it is sometimes the case that children experience obstacles, for example when their opinion, wishes and values are not heard and they are not included in decision making processes. For participation to be optimal and meaningful, health and social care professionals—including psychologists—need organisational, social, paediatric and pedagogical competence, critical awareness and reflection, and an openness to change in the practice and culture of service delivery (Quaye, Coyne, Soderback, 2019; Bijleveld, Bunders-Aelen, & Bedding, 2020; Bjønness, Viksveen, Johannessen, & Storm, 2020). Psychologists are increasingly asked to play a role in advancing the human rightsagenda. The APA suggests that we have a responsibility to advocate for the human rights of our patients, clients, students, research participants, and their families and communities of clients, including marginalised populations made vulnerable by societal inequalities (Huminiuk, 2023). As rights-based and person-centred paradigms become more central to our profession, there is a growing need to learn about human rights and how to integrate rights-based approaches with practice. In the Rep. of Ireland, rights-based practice is particularly important to children’s well-being and the protection of their right to the highest standard of health. Recently, the PSI explicitly stated that ‘children and young people who attend specialist mental health services … have the right to expect safe and effective support in a timely manner with their rights and needs at the centre of that care’ (PSI Statement, 2023). More than ever, psychologists are being asked to implement a rights-based approach for children— one that integrates equality, equity or even freedom from discrimination to the implementation and evaluation of mental health programmes (e.g. Mental Health Commission, 2023). In this article, we focus on legal frameworks and principles helpful to the implementation of children’s participation rights. We set out some practical ways for psychologists to start engaging with, or reflecting on, rights-based approaches in theory and practice

Association of Multiple Sclerosis Susceptibility Variants and Early Attack Location in the CNS

Objective: The anatomic location of subsequent relapses in early multiple sclerosis (MS) appears to be predicted by the first attack location. We sought to determine if genetic polymorphisms associated with MS susceptibility are associated with attack location. Methods: 17 genome-wide association study-identified MS susceptibility polymorphisms were genotyped in 503 white, non-Hispanic patients seen within a year of MS onset. Their association with the CNS location of the first two MS attacks was assessed in multivariate repeated measures analyses (generalized estimating equations with robust standard errors). Results: The IL12A polymorphism was independently associated with increased odds of attacks involving the spinal cord (OR = 1.52, 95% CI 1.11, 2.07, p = 0.009), as was the IRF8 polymorphism (OR = 2.40, 95% CI [1.04, 5.50], p = 0.040). The IL7R polymorphism was associated with reduced odds of attacks involving the brainstem/cerebellum (OR = 0.46, 95% CI 0.22, 0.97, p = 0.041), as were the TNFRSF1A and IL12A polymorphisms. The CD6 polymorphism conferred reduced odds of optic neuritis as an attack location (OR = 0.69, 95% CI [0.49, 0.97], p = 0.034). Several other genes showed trends for association with attack location. Conclusions: Some of the MS susceptibility genes may be associated with MS attack location. The IL12A polymorphism is of particular interest given that interferon beta therapy appears to influence IL12 levels. These findings may lead to improved understanding of MS pathogenesis and treatment

Decline in CD4 T lymphocytes with monotherapy bridging strategy for non-adherent adolescents living with HIV infection: Results of the IMPAACT P1094 randomized trial

Introduction Management of persistently non-adherent youth living with HIV (YLHIV) with virologic failure (VF) on combination antiretroviral therapy (cART) remains challenging. One strategy has been using 3TC/ FTC monotherapy (3TC/FTC), which in the presence of the M184V resistance mutation, does not suppress viral replication nor select for additional drug resistance mutations, and reduces viral fitness with limited side effects. P1094 compared the immunologic outcome of continuing failing cART vs. switching to 3TC/FTC as a “bridging strategy” to subsequent suppressive cART for non-adherent YLHIV with pre-existing M184V resistance. Materials & methods Participants with documented nonadherence, M184V mutation, CD4+ T cell count ≥100 cells/mm3 and VF (HIV-1 plasma RNA ≥400 copies/mL (2.6 log10 HIV-1 RNA) were enrolled and randomized to continue failing cART vs. switch to 3TC/FTC. The primary endpoint (time to ≥30% CD4+ T cell decline or development of CDC class C events) at 28-weeks were assessed by Kaplan-Meier (K-M) curves in an intent-to-treat analysis. Results Thirty-three perinatally acquired YLHIV participants (16 continuing cART and 17 3TC/FTC) enrolled in the study. The median age, entry CD4+ T cell count, and viral load were 15 years (Inter-quartile range (IQR) 14–20), 472 cells/mm3 (IQR 384–651), and 4.0 log10HIV-1 RNA copies/ml (IQR 3.2–4.5), respectively. Five participants, all in the 3TC/FTC arm, reached the primary endpoint for absolute CD4+ T cell decline (p = 0.02, exact log-rank test comparing monotherapy to cART). The Kaplan-Meier estimate of probability of primary endpoint on 3TC/FTC at 28 weeks was 0.41 (standard error 0.14). There were no CDC class C events or deaths and no statistically significant difference in frequencies of adverse events between the arms. Conclusions Non-adherent participants randomized to 3TC/FTC were more likely than those maintained on failing cART to experience a confirmed decline in CD4+ count of ≥30%. Although this study suffers from limitations of small sample size and premature discontinuation, the randomized comparison to continuing failing cART indicates that 3TC/FTC provides inferior protection from immunologic deterioration for non-adherent youth with M184V resistance. Better alternatives to 3TC/FTC such as ART with higher barriers to resistance and novel adherence and treatment strategies for nonadherent youth are urgently needed

Tumor Evolution in Two Patients with Basal-like Breast Cancer: A Retrospective Genomics Study of Multiple Metastases

Metastasis is the main cause of cancer patient deaths and remains a poorly characterized process. It is still unclear when in tumor progression the ability to metastasize arises and whether this ability is inherent to the primary tumor or is acquired well after primary tumor formation. Next-generation sequencing and analytical methods to define clonal heterogeneity provide a means for identifying genetic events and the temporal relationships between these events in the primary and metastatic tumors within an individual

Integrated RNA and DNA sequencing reveals early drivers of metastatic breast cancer

Breast cancer metastasis remains a clinical challenge, even within a single patient across multiple sites of the disease. Genome-wide comparisons of both the DNA and gene expression of primary tumors and metastases in multiple patients could help elucidate the underlying mechanisms that cause breast cancer metastasis. To address this issue, we performed DNA exome and RNA sequencing of matched primary tumors and multiple metastases from 16 patients, totaling 83 distinct specimens. We identified tumor-specific drivers by integrating known protein-protein network information with RNA expression and somatic DNA alterations and found that genetic drivers were predominantly established in the primary tumor and maintained through metastatic spreading. In addition, our analyses revealed that most genetic drivers were DNA copy number changes, the TP53 mutation was a recurrent founding mutation regardless of subtype, and that multiclonal seeding of metastases was frequent and occurred in multiple subtypes. Genetic drivers unique to metastasis were identified as somatic mutations in the estrogen and androgen receptor genes. These results highlight the complexity of metastatic spreading, be it monoclonal or multiclonal, and suggest that most metastatic drivers are established in the primary tumor, despite the substantial heterogeneity seen in the metastases

Zombie journals: designing a technological infrastructure for a precarious graduate student journal

Open access article. Creative Commons Attribution Non-commercial License (CC-BY-NC) applies.Background: The Meeting of the Minds graduate student journal is edited primarily by students from our Masters programme. This means that our editorial board is subject to high annual turnover and that our technological infrastructure and workflow needed to be easy to train for, accommodate differing levels of technological skill and editorial interest, and provide archiving that did not require a continuing interest in the journal by future generations of students. Analysis: This article provides a detailed and comparative account of the "off-the-shelf" systems and software used in developing the journal with an explanation of the rationale behind our choices. Conclusion and implications: The choices we made can be adopted by other journals interested in a low-cost, "future-proof" approach to developing a publishing infrastructure.Ye

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN