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Intervention to optimise body mass index in adolescents and address the triple burden of malnutrition-the Ntshembo (Hope) trial in rural and urban South Africa study: a study protocol for a randomised controlled trial.
No full textINTRODUCTION: South Africa faces a complex health burden with burgeoning non-communicable diseases against a background of prevalent infection. The triple burden of malnutrition, comprising undernutrition alongside overweight/obesity and micronutrient deficiencies, is widespread and imposes risks for non-communicable diseases along the life course, especially among adolescent girls. We hypothesise that, by optimising nutrition and body mass index (BMI) of at-risk adolescent girls, we can realise a triple return on investment: improved nutritional status, reduced metabolic risk, and moderated pre-conception exposures to offset transgenerational risk for cardiometabolic disease. METHODS AND ANALYSIS: We will enrol 1248 girls 14-19 years with either underweight or overweight defined using age-sex-appropriate BMI cut-offs living either in rural or urban South Africa. After baseline assessments and randomisation, participants will be reassessed at 18-24 months follow-up. If a participant becomes pregnant, further assessments will be conducted during pregnancy (< 28 weeks) and postnatally. We will include both process and economic evaluations. The primary outcome is change in BMI standard deviation score from baseline to follow-up aligned to the target direction, i.e. increase in BMI for underweight, decrease in BMI for overweight. Community health workers will deliver the intervention with both household and individual components. A conditional cash transfer will be provided to the household with guidance to improve dietary diversity. Health literacy material, a multi-micronutrient supplement, health screening and support management (for example anaemia; blood pressure; HIV; depression), and facilitating behaviour change to optimise nutrition, physical and mental health will be provided to the adolescent girl. TRIAL REGISTRATION: The trial has been registered with the Pan African Clinical Trials Registry; identifier: PACTR202201638897606. Registered on 1st August 2022. https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=14656
How Changing the Bridgehead Can Affect the Properties of Tripodal Ligands
No full textAbstract Although a multitude of studies have explored the coordination chemistry of classical tripodal ligands containing a range of main‐group bridgehead atoms or groups, it is not clear how periodic trends affect ligand character and reactivity within a single ligand family. A case in point is the extensive family of neutral tris‐2‐pyridyl ligands E(2‐py) 3 (E=C−R, N, P), which are closely related to archetypal tris‐pyrazolyl borates. With the 6‐methyl substituted ligands E(6‐Me‐2‐py) 3 (E=As, Sb, Bi) in hand, the effects of bridgehead modification alone on descending a single group in the periodic table were assessed. The primary influence on coordination behaviour is the increasing Lewis acidity (electropositivity) of the bridgehead atom as Group 15 is descended, which not only modulates the electron density on the pyridyl donor groups but also introduces the potential for anion selective coordination behaviour
Too late for CCS and hydrogen
No full textFifty years after carbon capture and storage (CCS) was commercialized, global capacity has reached just 0.09% of global emissions; even if installation rates immediately expand 10-fold, this will make no quantitatively important contribution to climate mitigation by 2050. Deployment of emission-free electricity generation is also constrained, so there will be no quantitatively important supply of hydrogen or negative-emission technologies by 2050 either, and climate policy must turn to other more achievable options. The bulk materials must be produced without process emissions, powered solely by emission-free electricity, within a constrained global electricity budget. Primary production of steel and paper can be fully electrified, although the electrical intensity of green hydrogen will constrain new steel processes. However, steel, aluminum, glass, plastic and potentially cement can all be recycled without emissions and with high efficiency. This reality should direct research toward improving the quality of recycled production, making better use of less material, and should be central to any advice given by academics to the policy community
Taking the direct route: menin inhibitors go straight to the frontline in KMT2A-rearranged acute leukemia.
No full textMenin inhibitors disrupt oncogenic transcription in KMT2A-rearranged leukemias, but responses are heterogeneous. A previous study highlighted the role of nongenetic resistance driven by altered chromatin context, including loss of KMT2C/D-UTX activity, underscoring the need for broader epigenetic profiling to guide therapy timing and combination strategy selection
Guest Binding via N−H⋅⋅⋅π Bonding and Kinetic Entrapment by an Inorganic Macrocycle
No full textAbstract : Modern supramolecular chemistry is overwhelm- ingly based on non-covalent interactions involving organic architectures. However, the question of what happens when you depart from this area to the supramolecular chemistry of structures based on non-carbon frameworks remains largely unanswered, and is an area that potentially provides new directions in molecular activation, host–guest chemistry, and biomimetic chemistry. In this work, we explore the unusual host–guest chemistry of the pentameric macrocycle [{P(m- NtBu}2NH]5 with a range of anionic and neutral guests. The polar coordination site of this host promotes new modes of guest encapsulation via hydrogen bonding with the p systems of the unsaturated CC and CN bonds of acetylenes and nitriles as well as with the PCO anion. Halide guests can be kinetically locked within the structure by oxidation of the phosphorus periphery by oxidation to PV. Our study under- scores the future promise of p-block macrocyclic chemistry
Acheulean expediency potential: handaxe manufacturing time costs, covariates and skill
No full textDespite decades of replicative experiments, the fundamental question “how long did it take to make an Acheulean handaxe” remains poorly understood. Archaeologists routinely base influential Pleistocene behavioral theory on lithic-related time budget considerations, so it is important to accurately understand their possible manufacturing costs. Here, we synthesize data from 227 handaxes manufactured by experienced, apprentice, and novice knappers. We record the duration of, and number of flake removals associated with, each handaxe, along with the duration of flake removal intervals and diverse covariate data. Experienced individuals were quicker, displayed briefer flaking intervals, and often removed fewer flakes, while inexperienced individuals were comparatively inefficient in multiple ways. Social environment, final handaxe form, and whether a target-shape was followed also impacted data, while handaxes produced under time pressure reveal the technologies’ expediency potential. Handaxe manufacturing costs are, therefore, highly context dependent, but were likely lower for Acheulean hominins than past work suggests
Genotype-Phenotype Maps of RNA: Evolution of Phenotypic Diversity and Plasticity
No full textThe genotype–phenotype (GP) map provides a quantitative framework to investigate how genetic variation translates into phenotypic change, revealing structural features that constrain evolutionary dynamics by determining which phenotypes are accessible for selection in the first place. This thesis develops and applies theoretical and computational frameworks to quantify GP map structure, and explores how these constraints shape evolutionary outcomes for RNA secondary structure. First, we extend the deterministic GP map that maps each genotype to one phenotype to a more biologically realistic many-to-many GP map that can map genotypes to multiple probable phenotypes. We call this the non-deterministic genotype–phenotype (ND GP) map, and use it to investigate phenotypic plasticity from the stochastic nature of RNA folding driven by thermal fluctuations. We redefine the typical structural quantities of the GP map such as robustness and evolvability to account for probabilistic phenotypic assignments and validate our framework as an average of sampled deterministic counterparts. We also show that the ND GP map retains the GP map core structural properties observed in deterministic cases. Then, we apply the ND GP map to study the evolution of RNA plasticity under fluctuating environments. Simulations demonstrate that genotypes with optimal plasticity—characterized by balanced probabilities across two target structures—emerge most readily under rapid environmental switching, where multiple stochastic expressions allow favorable phenotypes to be selected. These results offer insights into how GP map structure facilitates plasticity evolution and correspond with observations of natural functional RNAs, particularly regulatory and viral RNAs, suggesting these may have evolved under fluctuating selection pressures. Next, we analyse GP map structure through phenotypic distance, quantifying how divergent phenotypes are from one another. Weighting phenotypes by their pairwise distances, we show that core structural properties remain valid, indicating that phenotypic distance is an intrinsic feature of GP map architecture. We also demonstrate that large phenotypic distance accessibility is correlated with site robustness, highlighting the role of unconstrained sites in generating novelty. Finally, we find that in the ND GP map, fractional evolvability shows a scaling relationship with phenotypic frequency. We propose using phenotypic frequency as a proxy for evolvability estimation and outline potential extensions of these findings through site-scanning approaches that can be tested empirically and validated using our newly found relationship
Mindfulness-based psychoeducation app to improve the wellbeing of parents and caregivers of children with autism: A development and usability study
No full textBackground:
Autism spectrum disorder (ASD) does not only affect a person’s social Communication and behaviours, but also have an impact on their parents who encounter different challenges during caregiving. Interventions developed for parents of children with ASD often focus on improving child outcomes and seldom consider the wellbeing of parents and families. Interventions leveraging mindfulness-based approaches have been developed to support parents of children with ASD, but the costs, inflexibility, and scarcity of resources may limit their accessibility. App-based interventions can be an accessible, scalable, and economical way of providing interventions on a primary healthcare level.
Objective:
This study aimed to develop an evidence-based digital intervention, the TRIP app, that complements existing, overloaded psychiatric services for mindfulness-based psychoeducation to support parents of children with ASD and improve their mental wellbeing.
Methods: The app development process follows the systematic approach of intervention mapping (IM). Needs assessment was Zirst conducted through semi-structured qualitative interviews with healthcare professionals. Performance and change objectives were specified; theory-based and practical application methods were selected, followed by the design of the curriculum for the structured intervention. A pilot randomised waitlist controlled trial (RCT) was conducted to evaluate the feasibility, acceptability, and preliminary efficacy of the TRIP app with parents of children with ASD recruited from a tertiary child psychiatric service in Hong Kong.
Results:
The TRIP app is a 6-week structured intervention consisting of six sessions per
week, lasting 15-20 minutes each session, covering education on ASD parenting skills and mindfulness practices. The six weekly themes include 1) cultivating curiosity in
parenting, 2) mindfulness of the breath and body, 3) management of core and associated features of ASD, 4) managing conflicts and setting boundaries, 5) perspective taking, and 6) cultivating self-compassion. The curriculum and content were designed to target the determinants of parental stress, including knowledge, skills, emotions, and attitudes. App content and features were designed to incorporate behavioural change techniques, social cognitive theory, and elaboration likelihood model, so as to enhance efficacy and promote sustained usage of the app. The app was found to be feasible and acceptable in the pilot RCT (n = 40), with greater sustained usage amongst parents of children who were on the waiting list and were yet to receive services, including their diagnoses, when compared with parents of children who are already receiving clinical care.
Conclusions:
The TRIP app was developed based on existing knowledge and is contextualised to parents’ busy everyday lives. It caters the unmet needs for improving
caregiver wellbeing in the holistic care model for families of children with ASD. The
clinical efficacy of the TRIP app is yet to be evaluated through clinical trials
Serum biomarker trajectory clusters predict functional outcome and quality of life for traumatic brain injury.
No full textSerum brain-enriched biomarkers are increasingly employed in the clinical evaluation of traumatic brain injury (TBI) to assist with triage, neuroimaging decisions, and prognostication. However, the potential of temporal biomarker trajectories to inform disease monitoring and long-term outcomes remains underexplored. We aim to identify distinct biomarker trajectory (TRAJ) profiles in traumatic brain injury patients and to examine their associations with long-term clinical outcomes. The study included 373, CT-positive Intensive Care Unit (ICU) traumatic brain injury patients (256 with initial Glasgow Coma Scale 3-12) from the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) core study who had at least two serum samples collected between days 1 and 5 post-injury. Six biomarkers -glial fibrillary acidic protein, ubiquitin C-terminal hydrolase-L1, neurofilament light chain, Tau, S100B, and neuron-specific enolase- were analysed. Optimal cluster solutions were determined using a composite validation index derived from seven internal clustering metrics. Distinct high and low trajectory classes emerged for all biomarkers; each comprising at least 40% of the cohort for five of the biomarkers. Cross-biomarker concordance analysis identified composite high (n = 104) and low (n = 110) TRAJ profiles. Key metrics for evaluating patient outcomes include Glasgow Outcome Scale Extended (GOSE), mortality, and Quality of Life after Brain Injury Overall Scale (QoLIBRI-OS) at 3, 6, and 12 months as well as a prognostic incremental value analysis using a conventional prediction model: International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT). High TRAJ membership is strongly associated with poor functional recovery (GOSE 1-4 at 3-12 months; odds ratio (OR) 8.79 [95% confidence interval (CI): 4.56-16.97]-12.29 [95%CI: 6.19-24.40], P < 0.001) and increased 180-day mortality (OR (14.84 [95%CI: 5.56-39.64], P < 0.001). Conversely, low TRAJ membership predicted favourable recovery (GOSE 6-8 at 3-12 months; OR 7.42 [95%CI: 3.10-17.76]-10.83 [95%CI: 3.65-32.14], P < 0.001) and better quality of life (QoLIBRI-OS ≥52; OR 4.98 [95%CI: 1.92-12.89], P < 0.01). Compared to single day-1 biomarker measurements, trajectory-based profiles yielded larger effect sizes and provided incremental prognostic value when added to the IMPACT prediction model (ΔR² 9-17%, P < 0.05). Overall, repeated biomarker measurements across the acute phase yield superior prognostic accuracy relative to single timepoint assessments. These findings underscore the importance of integrating longitudinal biomarker monitoring into ICU-based traumatic brain injury care and suggest that temporal trajectory profiling may improve prognostic modelling and facilitate more precise patient stratification for both clinical management and interventional studies
Health Assessment of Underground Power Cables: A Data-Driven Approach Based on One-Sample Maximum Mean Discrepancy
No full textEffective health assessment and management of underground power cable system is essential for ensuring the cost-efficient operation of power grids. Existing practices usually monitor condition of the overall health of the power cable circuits but overlook its intricate structural complexity. This letter proposes a data-driven health assessment method considering both failure-related structural characteristics of each cable circuit and condition measurement data. Firstly, distinguishing failure indicators are identified by integrating in-depth component analysis with circuit condition measurements. Based on these features, a novel integrated health index is proposed, named as One-sample Maximum Mean Discrepancy (O-MMD), which evaluates the health condition of a circuit by quantifying the disparity between un-faulted assets and typical faulted groups in a high-dimensional feature space. This approach is able to assess whether new or modified circuits might exhibit similar fault characteristics as previously observed cases. Based on the O-MMD index, the probability of failure can be estimated for each cable circuit, and the maintenance plan can be prioritized. The proposed method is demonstrated on both seen and unseen real-world underground cable system data in Singapore