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Moving forward: a call for Critical ADHD Studies
Get PDFHighly effective early autistic activism gave considerable impetus to changes in the way autism research is conceived and carried out, notably through Critical Autism Studies (CAS). Little, though, has been similarly formalised challenging pathology-driven views of other forms of neurodivergence in research. However, there are increasing signs that this is changing, perhaps most particularly concerning ADHD. Here, we propose a tentative outline for what a Critical ADHD Studies – drawing on, bleeding into, and yet retaining its own specificities from both CAS and emergent Neurodiversity Studies – might resemble. This is neither a gate-keeping exercise nor a definitive mapping out of a field. Neither is ‘critical’, here, concerned with discussion of the validity of ADHD diagnoses. Rather, we seek points of intersection and of potential ally-ship, pulling together approaches centring ADHD lived experience, depathologisation, and ADHD affirmative world-making with related fields such as CAS and Neurodiversity Studies.<br/
Experimental evidence of vaccine-driven evolution of PRRSV-2
Get PDFDespite extensive use of vaccination, porcine reproductive and respiratory syndrome virus type 2 (PRRSV-2) continues to evolve, likely driven by escape from natural or vaccine-derived immunity. However, direct evidence of vaccine-induced evolutionary pressure remains limited. Here, we tracked the evolution of PRRSV-2 sublineage 1A strain IA/2014 (variant 1A-unclassified) genome from infection chains of sequentially infected pigs under different immune conditions. Weaned pigs were divided into three groups: a non-immunized control group and two groups vaccinated with different modified live virus (MLV) vaccines, namely Prevacent® PRRS MLV (variant 1D.2) and Ingelvac PRRS® MLV (variant 5A.1). Sixty-four days post-vaccination, the pigs were challenged with IA/2014 PRRSV-2. Virus infection chains (which used serum from pigs in batch n to infect batch n + 1) were maintained across six sequential batches of roughly seven pigs each, allowing for virus evolution to occur across the ~ 84 days of the infection chain. A total of 110 serum samples were successfully sequenced. Vaccinated groups exhibited over twice the genetic divergence from the original challenge virus (0.3%-0.4% mean nucleotide distance) compared to non-immunized group (0.15%). Variability was concentrated in ORF1a and ORF1b. Deep sequencing revealed more rapid shifts of viral quasispecies composition in vaccinated pigs, and more homogeneous viral populations over batches compared to non-immunized pigs. Selection pressure analyses indicated strong purifying selection in one vaccinated group, though without clear signals at known antigenic sites in all treatment groups. However, vaccinated pigs had significantly higher cycle threshold values ( P<.001), indicating lower viral loads and suggesting potential fitness limitations for highly diverged viruses in immunized pigs. These findings demonstrate that MLV vaccination can exert substantial evolutionary pressure on PRRSV-2, driving genetic diversification and highlighting the need for continuous PRRS monitoring and adaptive control strategies. </p
The efficient tail hypothesis: an extreme value perspective on market efficiency
Get PDFIn econometrics, the Efficient Market Hypothesis posits that asset prices reflect all available information in the market. Several empirical investigations show that market efficiency drops when it undergoes extreme events. Many models for multivariate extremes focus on positive dependence, making them unsuitable for studying extremal dependence in financial markets where data often exhibit both positive and negative extremal dependence. To this end, we construct regular variation models on the entirety of R and develop a bivariate measure for asymmetry in the strength of extremal dependence between adjacent orthants. Our directional tail dependence (DTD) measure allows us to define the Efficient Tail Hypothesis (ETH) -- an analogue of the Efficient Market Hypothesis -- for the extremal behaviour of the market. Asymptotic results for estimators of DTD are described, and we discuss testing of the ETH via permutation-based methods and present novel tools for visualization. Empirical study of China's futures market leads to a rejection of the ETH and we identify potential profitable investment opportunities. To promote the research of microstructure in China's derivatives market, we open-source our high-frequency data, which are being collected continuously from multiple derivative exchanges
Eating disorder presentations to a child and adolescent mental health service in the UK before and during the COVID-19 pandemic
Get PDFPURPOSE: Previous studies have reported an increase in new-onset adolescent eating disorder (ED) patients during the COVID-19 pandemic, with some studies showing a change in illness presentation. This study aimed to replicate and expand on previous work by further examining changes in illness and demographic characteristics.METHOD: Changes in the number of new ED referrals to a Child and Adolescent Mental Health Service were examined between 2019 and 2022. Additional analyses explored changes in duration of symptoms, weight-for-height, the need for more intensive care, age, and socioeconomic status. All analyses were conducted within the Bayesian framework.RESULTS: A total of 371 new ED referrals were seen during the study period, and a significant increase in new ED cases was observed during COVID-19. This increase was not driven by any particular diagnostic group. There was no evidence for meaningful changes in demographic or illness characteristics.CONCLUSIONS: These findings replicate previous work demonstrating a steady increase in ED patients during the pandemic. We did not find an accompanying change in illness characteristics. There was no significant change in the measure of patients' deprivation, suggesting that the pandemic did not widen the service access gap.</p
Serological diagnosis of cysticercosis in humans and pigs: status, limitations, and prospects
Get PDFCysticercosis is a neglected zoonosis caused by Taenia solium, which involves pigs as intermediate hosts, leading to pig cysticercosis (PCC). Humans are the only definitive hosts, harbouring the mature tapeworm in the small intestines, but they can also act as intermediate hosts upon accidental ingestion of eggs, resulting in human cysticercosis (HCC), called neurocysticercosis (NCC) when the cysts lodge in the central nervous system. Diagnosis of HCC/NCC in humans is based on imaging technologies and serology. The gold standard method for PCC diagnosis is the full carcass dissection and recovery of cysts. However, tongue palpation and meat inspection are the most widely used methods in endemic countries. These methods are specific at the genus level but cannot distinguish mixed infection from other taeniids and are not sufficiently sensitive in pigs with low infection. Available serological tests for human and pig infection are based on parasite-specific immunoglobulin G (IgG). Still, most tests are either cross-reactive with other taeniids or not sensitive enough for single or inactive cysts, particularly for NCC patients. Here, we compare various serological techniques for PCC and NCC published since 2000 and discuss the benefit of IgE-based serodiagnosis as a potential alternative to traditional serology. Considering the diagnostic limitations described above and the need to identify endemic areas to prevent transmission between humans and pigs and monitor control efforts, the development of more sensitive and specific serological tests, followed by a field-applicable point-of-care (POC) test for cysticercosis, is of the utmost importance.</p
Creative experiences and brain clocks
No full textCreative experiences may enhance brain health, yet metrics and mechanisms remain elusive. We characterized brain health using brain clocks, which capture deviations from chronological age (i.e., accelerated or delayed brain aging). We combined M/EEG functional connectivity (N = 1,240) with machine learning support vector machines, whole-brain modeling, and Neurosynth metanalyses. From this framework, we reanalyzed previously published datasets of expert and matched non-expert participants in dance, music, visual arts, and video games, along with a pre/post-learning study (N = 232). We found delayed brain age across all domains and scalable effects (expertise>learning). The higher the level of expertise and performance, the greater the delay in brain age. Age-vulnerable brain hubs showed increased connectivity linked to creativity, particularly in areas related to expertise and creative experiences. Neurosynth analysis and computational modeling revealed plasticity-driven increases in brain efficiency and biophysical coupling, in creativity-specific delayed brain aging. Findings indicate a domain‑independent link between creativity and brain health.</p
Intermolecular Sp<sup>3</sup>C─H Metalation of Non-Nucleophilic Brønsted Bases Using Simple Lewis Acids
No full text2,6-Di-tert-butyl substituted pyridines (tBu2-py) are widely used non-nucleophilic Brønsted bases. Their ubiquity is due to their highly hindered basic site and chemically robust nature. Herein we report that simple M2X6 Lewis acids (M═Al or Ga, X═Cl, Br or I) effect intermolecular sp3C─H metalation of tBu2-py bases under mild conditions. The sp3C─H metalated products can be converted in situ into ─BPin, ─iodo, ─bromo and ─hydroxy derivatives for further elaboration. Mechanistic investigations indicate that: i) a frustrated Lewis pair effects sp3C─H heterolysis to form the C─M bond and a protonated pyridine; ii) C─H metalation requires singly halide-bridged super-electrophilic M2X6 dimers for sufficiently low barriers. Finally, sp3C─H metalation using M2X6 is not limited to tBu2-py bases. Thus, it is important to be aware of this facile sp3C─H functionalisation when using a range of non-nucleophilic Brønsted bases.</p
Multiregional blood-brain barrier phenotyping identifies the prefrontal cortex as the most vulnerable region to ageing in mice
No full textAge-associated vascular alterations make the brain more vulnerable to neuropathologies. Research in humans and rodents have demonstrated structural, molecular, and functional alterations of the aged brain vasculature that suggest blood-brain barrier (BBB) dysfunction. However, these studies focused on particular features of the BBB and specific brain regions. Thus, it remains unclear if and which BBB age-associated phenotypes are conserved across brain areas. Moreover, there is very limited information about how BBB dysfunction and cell-specific phenotypes relate to each other. In this manuscript, we use immunofluorescence, transmission electron microscopy (TEM), and permeability assays to assess how age-associated BBB molecular, structural, and functional phenotypes correlate between the BBB cell types at three brain regions (prefrontal cortex, hippocampus, and corpus callosum) during mouse early ageing. We discovered that at 18-20 months of age, changes to the mouse BBB are subtle. The prefrontal cortex BBB is the most affected by age, with alterations in brain endothelial cell protein expression, BBB permeability, basement membrane thickness, and astrocyte endfoot size when compared to young mice. Here, we deliver a detailed multicellular characterisation of region-dependent BBB changes at early stages of ageing. Our data paves the way for future studies to investigate how region-specific BBB dysfunction may contribute to disease-associated regional vulnerability
Telomere-Related Gene Networks in the Ovary Shift Across Environmental Factors
No full textThe ovary is key to linking environmental factors with the timing and quality of offspring development. Focused on free-living female tree swallows (Tachycineta bicolor), we measured temporal variation in ovarian expression of genes involved in the regulation of telomere length. Using qPCR, we quantified mRNA abundance of shelterin proteins (TERF1, TERF2, TERF2IP, TPP1, POT1), telomerase (TERT), antioxidants (SOD1, PRDX-1, GPX), and glucocorticoid receptors (MR, GR). We asked how they differ across breeding stages and social environments, and then we assessed effects on gene co-expression, which reflects coordinated changes across this network of interacting genes. We hypothesized that maintenance of telomeres is upregulated and more strongly coregulated in the lead up to reproduction, i.e., before egg-laying and following a social challenge. We did not find a main effect of environmental context on mRNA abundance, but we did detect subtle differences in gene co-expression networks. Females exhibited stronger coregulation among shelterin proteins and stronger crosstalk with glucocorticoid receptors during incubation. In response to a conspecific challenger, coregulation of antioxidants with shelterin and glucocorticoid receptors was weaker or more negatively correlated, suggesting semi-independent social modulation of these telomere regulatory networks. While the consequences of these transcriptional differences require more research, our results suggest that the environment could contribute to protection of the ovary, including its telomeres.</p
Assessing gecko susceptibility to international wildlife trade: A novel trait-based framework
No full textInternational wildlife trade (IWT) drives biodiversity loss, often affecting species before they are formally assessed or well-known, particularly newly described ones. These species can be traded without consequence due to a lack of prior knowledge or legal protection and reptiles, especially geckos, face pressure from the exotic pet and traditional medicine trades.We developed a Wildlife Trade Susceptibility Framework (WTSF), adapting trait-based methods from climate change vulnerability assessments to evaluate how species traits influence their desirability and exposure to trade. We applied the WTSF to 1886 known gecko species, a group heavily targeted by IWT. The framework identified 48 % of species as highly susceptible to trade. Key traits linked to susceptibility included evolutionary distinctiveness and body mass. Regions with the highest concentrations of susceptible and sensitive species included Madagascar, Southeast Asia, and New Guinea.A third of the most sensitive gecko species are absent from current trade databases, likely due to low demand, limited accessibility, or effective enforcement. This absence highlights the limitations of existing species knowledge and monitoring in identifying those most at risk from IWT. Our framework provides an early warning system to flag biologically susceptible species before they appear in trade and can be applied across taxonomic groups
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