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Landscape evolution of the Bolivian Amazon controlled by uplift events dated 13,000, 10,000 and 6000 cal yr BP
Get PDFThe Llanos de Moxos in the Bolivian Amazon, the second largest South American wetland, hosts many endemic species and a rich archaeological record that spans the entire Holocene. Despite its ecological and archaeological importance, very little is known about its Holocene environmental history. A growing body of evidence suggests that neotectonics played an important role in shaping its modern landscape and controlling past flooding dynamics, but the chronology and vertical displacements of past tectonic events are still largely unknown. Here, we present new data from a core taken at Lake Oceano, a large ria lake in the northern part of the Llanos de Moxos. To identify changes in the lithology and environment, we performed a battery of analyses, such as XRF scanning, mineralogy, granulometry, C/N and C and N stable isotopes, and also built an age-depth model using eighteen radiocarbon dates obtained from accelerator mass spectrometry (AMS) determinations. Based on the sedimentology and chemical analyses, we identified three major disturbances in the lake sedimentation that we interpret as positive tectonic events (i.e., tectonic uplifts). The first identified event occurred at approximately 13,400 cal yr BP and led to the formation of the lake by blocking the river course. A second uplift event took place around 10,000 cal yr BP, accompanied by a significant change in the geochemistry of the lake sediments. Furthermore, we have verified a third event at 6000 cal yr BP, previously recognized as responsible for the onset of Lake Rogaguado (aprox. 100 km NE of Lake Oceano), one of the largest lakes in South America. Overall, we show that ria lakes can provide key sedimentary archives to reconstruct the past timing and intensity of tectonic events. We discuss the interplay between tectonics and climate, highlighting the connection between tectonics and the region's flood history, with crucial implications for the interpretation of both archaeological and palaeoecological records throughout the Holocene
Antiviral efficacy of fluoxetine in early symptomatic COVID-19: an open-label, randomised, controlled, adaptive platform trial (PLATCOV)
Get PDFBackgroundThe selective serotonin reuptake inhibitors (SSRIs) fluoxetine and fluvoxamine were repurposed for the treatment of early COVID-19 based on their antiviral activity in vitro, and observational and clinical trial evidence suggesting they prevented progression to severe disease. However, these SSRIs have not been recommended in therapeutic guidelines and their antiviral activity in vivo has not been characterised.MethodsPLATCOV is an open-label, multicentre, phase 2, randomised, controlled, adaptive pharmacometric platform trial running in Thailand, Brazil, Pakistan, and Laos. We recruited low-risk adult outpatients aged 18–50 with early symptomatic COVID-19 (symptoms 2 days follow-up).The viral clearance rate was estimated under a Bayesian hierarchical linear model fitted to the log10 viral densities measured in standardised duplicate oropharyngeal swab eluates taken daily over one week (18 measurements per patient). Secondary endpoints were all-cause hospital admission at 28 days, and time to resolution of fever and symptoms. This ongoing trial is registered at ClinicalTrials.gov (NCT05041907).Findings271 patients were concurrently randomised to either fluoxetine (n = 120) or no study drug (n = 151). All patients had received at least one COVID-19 vaccine dose and 67% were female (182/271). In the primary analysis, viral clearance rates following fluoxetine were compatible with a small or no increase relative to the no study drug arm (15% increase; 95% credible interval (CrI): −2 to 34%). There were no deaths or hospitalisations in either arm. There were no significant differences in times to symptom resolution or fever clearance between the fluoxetine and the no study drug arms (although only a quarter of patients were febrile at baseline). Fluoxetine was well tolerated, there were no serious adverse events and only one grade 3 adverse event in the intervention arm.InterpretationOverall, the evidence from this study is compatible with fluoxetine having a weak in vivo antiviral activity against SARS-CoV-2, although the primary endpoint is also compatible with no effect. This level of antiviral efficacy is substantially less than with other currently available antiviral drugs.FundingWellcome Trust Grant ref: 223195/Z/21/Z through the COVID-19 Therapeutics Accelerator
Can we constrain geographical variability in the biological carbon pump's transfer efficiency from observations?
Get PDFThe biological carbon pump (BCP) transfers large amounts of carbon from the atmosphere into the ocean's interior, contributing to carbon sequestration. Studies on latitudinal variability in organic carbon transfer to depth have yielded inconsistent results, likely due to methodological differences. To address this, we compiled particulate organic carbon (POC) flux data and BCP metrics from time-series locations across biogeographically distinct ocean regions. We integrated multiple BCP observational techniques, including diverse collection and processing protocols, capturing diverse facets of POC flux at varying spatio-temporal resolutions. To ensure comparability, we harmonized errors and used Monte Carlo error propagation to calculate uncertainties consistently. Our analysis reveals large local uncertainties that obscure expected latitudinal variations in BCP metrics. While such variations may exist, they remain difficult to identify with current observational data. Our findings underscore the need for sustained POC flux observations, standardization of protocols, and intercalibration of technologies to identify geographic BCP patterns
Psychological flexibility in caregivers of children with congenital craniofacial conditions in the United Kingdom
Get PDFObjectives: Some children born with a craniofacial condition, and their caregivers, can experience psychological difficulties. Psychological flexibility involves responding to internal distressing experiences (eg, emotions) with openness rather than avoidance, being present-focused, and behaving in ways that align with personal values. Psychological flexibility is typically associated with greater psychological well-being. The current study aimed to investigate whether psychological flexibility in caregivers of a child with a congenital craniofacial condition was associated with caregiver and child psychological well-being, to inform the development of interventions likely to help caregivers. It was hypothesized that higher levels of both general and parenting-specific psychological flexibility would be associated with greater psychological well-being in both caregivers and children.
Design: A cross-sectional questionnaire study.
Setting: Questionnaires were completed online.
Participants: Caregivers (N = 89) of children aged 1-5 years with a congenital craniofacial condition.
Main outcome measure(s): Questionnaires measuring psychological flexibility, parenting-specific psychological flexibility, caregiver depression and anxiety, and caregiver-reported child well-being.
Results: Correlational and linear regression analyses revealed that higher parenting-specific psychological flexibility in caregivers was associated with—and predictive of—lower depression and anxiety in caregivers, and greater well-being in children. Higher general psychological flexibility in caregivers was associated with—and predictive of—reduced caregiver depression and anxiety and increased child well-being.
Conclusions: Early identification of caregivers of children with craniofacial conditions exhibiting difficulties with parenting-specific psychological flexibility, and the provision of psychological interventions to enhance psychological flexibility (acceptance and commitment therapy), is indicated for benefiting caregiver and child well-being
Success – whose definition counts? A co-designed framework by and for young people leaving care
Get PDF‘Success – whose definition counts?’ set out to better understand how careexperienced young people define success - by asking them directly. Through this co-designed project, care leavers worked with researchers to challenge the assumptions built into existing practice and data systems and develop an alternative framework grounded in lived experience. Their work encourages professionals to reconsider what is being measured and why.Commissioned by Become and carried out by the Rees Centre at the University of Oxford, the project highlighted how limited and disconnected existing outcome measures are and offers a new approach – shaped by care-experienced young people – that reflects the complexity, context, and realities of their lives. The methodology comprised a literature review on how success is defined for young adults in the general population, a series of interviews with local and national professionals to assess existing outcome measures for care leavers and focus groups with 26 care-experienced young people to consider what success looks like for them. The findings were used to develop and test in five local authority areas a new interactive success measurement tool (the success survey) - to be completed by care leavers with their personal advisers (PAs) - that better reflects the goals, values and progress that matter most to care-experienced young people. Further focus groups (with 16 care leavers) and two cognitive interviews in the same local authorities helped to further refine the success survey and gather feedback on its completion. Throughout the project the research was shaped by a design group - named the Future of Care Design Group by its members - of 13 brilliant careexperienced young people
A Syriac pneumatological tradition in the writings of Gregory Nazianzen
No full textIn Hex. 2.6, Basil of Caesarea cites an unnamed Syrian in support of his account of the Spirit’s creative activity. As several scholars have noted, this passage represents a rare example of the transmission Westwards of theological motifs originally developed within a Syriac-speaking milieu. This paper will argue that another such example can also be found in the writings of Gregory Nazianzen. My argument focusses Gregory’s comparison of the Spirit’s generation to the generation of Eve from Adam’s side in Or. 31.11. In this passage, I argue, Gregory exhibits awareness of a Pneumatological themes of Syriac provenance which identifies the Spirit as (in some sense) ‘feminine’. While Alexander Golitzin has already suggested that Gregory’s argument in Or. 31.11 may reflect his familiarity with Syriac traditions regarding the ‘feminine Spirit’, he fails to identify the closest parallel to Gregory’s argument, which is to be found in Ephrem’s Commentary on the Diatessaron. I argue that Ephrem is most likely Gregory’s source in Or. 31.11, suggesting Ephrem’s (now no longer extant) treatise On the Holy Spirit as a possible source of transmission
TAOK2 controls synaptic plasticity and anxiety via ERK and calcium signaling
Get PDFThe kinase thousand and one amino acid kinase 2 (TAOK2) regulates dendritic architecture and synaptic plasticity and is implicated in neurodevelopmental and neuropsychiatric disorders, including autism and schizophrenia. Here, we investigated TAOK2 function by creating an Emx1-Cre-driven, excitatory-neuron-specific conditional Taok2 knockout (Taok2 cKO) mouse line. Pathway profiling in Taok2 cKO primary cortical neurons revealed impaired extracellular regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) and calcium signaling after AMPA, BDNF, or bicuculline stimulation. These results were validated by reduced p-ERK1/2 protein levels and decreased calcium flux. Cultured Taok2 cKO neurons displayed reduced synaptic density and connectivity. Single-nucleus RNA sequencing of medial prefrontal cortex identified dysregulated gene expression enriched for postsynaptic MAPK and calcium pathways within cortical layers 2/3 and 4/5. Taok2 cKO mice exhibited an anxiety-related thigmotactic behavior in the open field test. Our findings demonstrate that TAOK2 loss in excitatory cortical neurons disrupts synaptic signaling and connectivity, drives behavioral abnormalities, and positions TAOK2 as a potential drug target for neuropsychiatric disorders
Protocol: a systematic review+ (SR+) to combine associative and mechanistic evidence on the efficacy of face masks in reducing transmission of respiratory diseases
Get PDFBackground: Mechanistic evidence is evidence about how an intervention works. A 2023 Cochrane review, which was restricted to randomised controlled trials (RCTs), concluded that evidence on the efficacy of face masks was weak, conflicting and non-definitive. A 2024 narrative review, which included RCTs plus mechanistic evidence on masks and mask mandates, concluded that evidence of efficacy was strong, consistent and definitive. These strikingly contrasting conclusions reflect differences in how evidence is valued. Orthodox synthesis methods (e.g. those used for Cochrane reviews, informed by GRADE criteria) classify mechanistic evidence as lower quality than RCT evidence, but this position has been challenged by (among others) philosophers, non-RCT researchers and advocacy groups. We seek to include mechanistic evidence in a systematic review of mask efficacy. Method: Three overlapping work packages (methodology, review, philosophical analysis) will run concurrently. We will extend and refine the philosophical approach of Evidential Pluralism, which has been applied in a technique known as EBM+, to develop Systematic Review+ (SR+). SR+ will use Bayesian methods to support judgements of whether and to what extent interventions are effective. We will apply SR+ to face mask (and mask mandate) efficacy studies purposively selected for their epistemic contribution (the most robust and influential studies in each evidential category). We will consider whether SR+ adequately addresses philosophical objections to orthodox systematic review, including epistemological (does it adequately incorporate mechanistic evidence into reviews of efficacy?) and ethical (does it adequately address epistemic injustice, in which someone is wronged in their capacity as knower?). Discussion: We hope to produce a robust synthesis of evidence on face masks that will inform policy and a general methodology for incorporating mechanistic evidence into systematic reviews. We also hope to contribute to the scholarly literature on the philosophy of causality. Causal claims generally require at least two kinds of evidence: associative (to show that a change in one phenomenon is associated with a change in another) and mechanistic (to be confident that observed associations are causal). We hypothesise that orthodox systematic review, enhanced with mechanistic evidence, will be able to support stronger and more nuanced causal claims. Systematic review registration: INPLASY202550024, INPLASY202540045
Unlocking vehicle-to-grid potential of load shifting in China’s megacities considering comprehensive real-world behaviors
Get PDFGlobal decarbonization necessitates large-scale electrification, bringing load stability challenges to urban grids. While Vehicle-to-grid (V2G) technology using private plug-in electric vehicles (P-PEVs) can balance the loads, its potential at megacity-level remains unclear due to the complexity of fine-grained, user-centric modelling. Here, we propose a Mobility and V2G Coupled (MOVC) framework, which depicts individual P-PEV travel-charge behaviors and evaluates user V2G concerns regarding willingness, compensation, and battery degradation. The framework analyzes 480,000 P-PEVs in Shenzhen, China, revealing a 2300 MW peak-shaving capacity, reducing peak-valley ratios by 73%. V2G strategies that prioritize user satisfaction hardly sacrifice the load shifting performance, but reduce battery degradation costs and compensation costs by 30-40% and 5-13% respectively. A forward-looking scenario considering fully-deployed quick charging (QC) in four China’s megacities reveals 0%-12% lower peak-valley ratios with more inequal V2G scheduling (4%-95% higher standard deviation). This study enlightens megacity-level V2G potential evaluations and their policy-making considering real-world behaviors
Intercellular signaling and synaptic deconstruction uncovered by single-cell and spatial transcriptomics in an AD tauopathy model
Get PDFAlzheimer’s disease (AD) is the leading cause of dementia in elderly individuals worldwide; however, all mechanisms leading to disease onset and progression are not well understood. Here, we report brain single-cell multiome and spatial transcriptomics in a transgenic rat model of human-like tauopathy. We have identified new markers of tau-driven AD pathology and provided single-cell evidence for genes implicated in AD. Our findings reveal how tau hyperphosphorylation and aging alter ligand-receptor communication, transcription factor regulatory networks, and specific cellular networks. Notably, we found intriguing changes in cell communication involving glutamatergic transmission and Netrin signaling as a taupathy consequence. Overall, this study reinforces the concept that synaptic dysfunction is a critical early event in AD and highlights potential targets as potential therapeutic strategies