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Multiple pendants-bearing triglucosides for membrane protein studies: effects of pendant length and number on micelle interior hydration and protein stability
No full textMembrane proteins play central roles in cell physiology and are the targets of over 50% of FDA-approved drugs. In the present study, we prepared single alkyl-chained triglucosides decorated with multiple pendants, designated multiple pendant-bearing glucosides (MPGs), to enhance membrane protein stability. The new detergents feature two and four pendants of varying size at the hydrophilic–lipophilic interfaces, designated MPG-Ds and MPG-Ts, respectively. When tested with model membrane proteins, including the human adrenergic receptor (β2AR), the tetra-pendant-bearing MPGs (MPG-Ts) demonstrated superior performance compared to the dipendant analogs (MPG-Ds) and the gold standard DDM. All-atom molecular dynamics (MD) simulations results reveal that the four-pendant configuration of this detergent is remarkably effective in excluding water from the hydrophobic micelle interiors compared to the dipendant MPGs and DDM, an unprecedented feature of this new detergent. Our findings provide a novel strategy for designing water-resistant detergents, advancing the field of membrane protein research
Nomogram for estimating the risk of suicide attempts in major depressive disorder: integrating demographic, clinical and biochemical markers – a cross-sectional study
No full textBackground: Major depressive disorder (MDD) is a significant risk factor for suicide attempts (SA), making early identification of those most at risk crucial for effective clinical intervention. This study aimed to identify demographic, clinical, and biochemical correlates of SA among inpatients with MDD.
Methods: In this cross-sectional study, data were collected from 968 inpatients diagnosed with MDD, including 392 with documented suicide attempts (MDD-SA) and 576 without suicidal behaviors (MDD-NSA). Demographic characteristics, clinical history, and peripheral biochemical markers were analyzed using multivariable logistic regression to assess associations with SA. Variable selection was performed using penalized logistic regression with 10-fold cross-validation, and the selected variables were then entered into a binary logistic regression model to illustrate the relative contribution of significant factors. Model performance was evaluated using the area under the Receiver Operating Characteristic (ROC) curve, calibration plots, and decision curve analysis (DCA).
Results: Significant differences were found between MDD-S and MDD-N in marital status (42.3% vs. 57.7%, p = 0.004), alcohol consumption (15.82% vs. 8.85%, p < 0.001), tobacco use (20.67% vs. 13.73%, p = 0.004), education level (p < 0.001), life events (79.59% vs. 65.28%, p < 0.001), and folate levels (p < 0.001). MDD-S patients were more likely to undergo modified electroconvulsive therapy (61.73% vs. 39.41%, p < 0.001) and mood stabilizers (26.02% vs. 18.92%, p = 0.009). The nomogram incorporated tobacco use, alcohol consumption, education level, life events, and folate levels, showing good discrimination (C-index = 0.709, bootstrap = 0.703). ROC analysis demonstrated an AUC of 0.709 (95% CI: 0.677–0.742), and DCA confirmed clinical utility.
Conclusion: Several routinely available variables, including tobacco use, alcohol consumption, education level, life events, and folate level, were associated with suicide attempts in MDD inpatients. Our findings highlight these important correlates, which may help clinicians in recognizing patients at elevated risk. The nomogram provided in this study should be regarded only as a visualization to better illustrate the contribution of these factors, rather than as a clinical assessment tool. Prospective multicenter studies are needed for further validation
Advertising exposure and the appeal of emerging nicotine-containing products among people who have never used nicotine: findings from the Eurobarometer 2023
No full textIntroduction Emerging nicotine-containing products, including heated tobacco products (HTPs) and nicotine pouches, have been growing in popularity in the European Union (EU). Advertising exposure impacts perceived product appeal and may contribute to product initiation. However, the current EU’s Tobacco Products Directive lacks a consistent framework for regulating these advertisements. This study examines how exposure to HTP and nicotine pouch advertisements influences their appeal among people who have never used nicotine.
Methods Data from the Special Eurobarometer 99.3 survey (May–June 2023) included 13 436 participants who have never used nicotine across 27 EU Member States. We estimated the weighted prevalence of HTP and nicotine pouch advertising exposure and perceived appeal and ran multilevel Poisson regression models adjusting for sociodemographic factors.
Results 31.1% of participants reported HTP advertising exposure across the EU, with the highest levels reported in Romania (53.4%) and Slovakia (50.0%) and the lowest in Malta (13.6%). Nicotine pouch advertising exposure averaged 16.6%, peaking in Sweden (46.0%) and lowest in the Netherlands (5.0%) and Lithuania (7.7%). Product appeal remained low, with only 2.0% finding HTPs appealing and 1.3% finding nicotine pouches appealing. Exposed to HTP advertisements were 3.71 times more likely to find them appealing, while exposure to nicotine pouch advertisements increased perceived appeal of nicotine pouches by 5.78 times.
Conclusion Advertising exposure was associated with higher appeal of nicotine-containing products among people who have never used nicotine. Given the risk of initiation, EU-wide advertising restrictions could protect this group and limit the impact of these products on health
Exact solutions for laminar pressure-driven flow through a pipe with a concentric internal grating
No full textThis paper presents an analytical model for laminar pressure-driven axial flow along a circular pipe containing an internal concentric circular grating of no-slip fins. Explicit expressions for the velocity field are derived using complex analysis techniques and conformal mappings. From these solutions, formulas for the Fanning friction factor associated with axial flow in such finned pipes are derived and, using these, the drag properties of the pipes are examined. The results offer valuable insights for optimizing finned duct designs in applications involving heat transfer, fluid flow and biofilm cultivation
A prudent planetary limit for geologic carbon storage
No full textGeologically storing carbon is a key strategy for abating emissions from fossil fuels and durably removing carbon dioxide (CO2) from the atmosphere1,2. However, the storage potential is not unlimited3,4. Here we establish a prudent planetary limit of around 1,460 (1,290–2,710) Gt of CO2 storage through a risk-based, spatially explicit analysis of carbon storage in sedimentary basins. We show that only stringent near-term gross emissions reductions can lower the risk of breaching this limit before the year 2200. Fully using geologic storage for carbon removal caps the possible global temperature reduction to 0.7 °C (0.35–1.2 °C, including storage estimate and climate response uncertainty). The countries most robust to our risk assessment are current large-scale extractors of fossil resources. Treating carbon storage as a limited intergenerational resource has deep implications for national mitigation strategies and policy and requires making explicit decisions on priorities for storage use
The effectiveness of isoniazid preventive treatment among contacts of multidrug-resistant tuberculosis: a systematic review and individual-participant meta-analysis
No full textRationale: Recent empirical research suggests isoniazid may lead to a risk reduction of incident tuberculosis among close tuberculosis contacts of multi-drug resistant (MDR) tuberculosis. Objectives: To evaluate the association between isoniazid tuberculosis preventive treatment (TPT), compared to no treatment, upon incident tuberculosis in household contacts of MDR tuberculosis cases using a large global consortium of tuberculosis contact tracing studies. Methods: We conducted a systematic review and individual-participant meta-analysis among observational studies of household contact tracing studies. Participants were included if they were exposed to someone with MDR-tuberculosis and were given either 6 months of isoniazid TPT or no TPT. Our primary outcome was incident tuberculosis in contacts exposed to tuberculosis. We derived adjusted hazard ratios (aHRs) using mixed-effects, multivariable survival regression models with study-level random effects. The effectiveness of isoniazid TPT against incident tuberculosis was estimated through propensity score matching. We stratified our results by contact age, background tuberculosis burden, and Mycobacterium tuberculosis infection status. Measurements and Main Results: We included participant-level data from 6,668 contacts exposed to multidrug-resistant tuberculosis from 17 countries. The effectiveness of isoniazid TPT against incident tuberculosis in contacts of multidrug-resistant tuberculosis was 57% (aHR, 0.43; 95% CI, 0.26–0.71) and did not appreciably change with adjustment for additional potential confounders. The reduction in incident tuberculosis was marginally greater among child (<20 years old) contacts (0.51; 95% CI, 0.28–0.92) compared to adult contacts (0.69; 95% CI, 0.22–2.20). The reduction in incidence was 73% (0.27; 95% CI, 0.11–0.70) in the first year of follow-up; effectiveness dropped to 60% (0.40; 95% CI, 0.15–1.06) from 12–23 months of follow-up and was non-significant after two years (28% effectiveness; 0.72; 95% CI, 0.33–1.54). Conclusions: Among over 6,500 contacts of MDR-tuberculosis, isoniazid TPT was highly effective in preventing incident tuberculosis. The reduction was greatest in high-burden countries and waned after 2 years of follow-u
Oral immunotherapy in peanut‐Allergic adults using real‐world materials
No full textBackground
Peanut oral immunotherapy (OIT) has shown effectiveness in achieving desensitization of children; however, evidence in adults is lacking.
Methods
This phase II trial evaluated peanut OIT in peanut-allergic adults using real-world peanut products. A Simon's minimax two-stage design, incorporating a stop:go for futility, was employed. A separate untreated control group was also recruited for comparison of mechanistic parameters. Participants underwent baseline double-blind placebo-control food challenges (DBPCFC) with peanut protein doses of 0.3 to 300 mg. Reacting participants were initiated on daily OIT with 2-weekly updosing until reaching a maintenance dose of 1000 mg (four large peanuts). The primary outcome was the proportion of OIT participants who tolerated a cumulative dose of 1.4 g peanut protein during exit DBPCFC (doses provided 0.3-3000 mg).
Results
Twenty-one adults (8 female; mean age 24.2 years [SD 4.9]) were enrolled in the OIT group, with 67% achieving the daily maintenance dose and meeting the primary endpoint. Three withdrew due to adverse reactions, and a further three did not complete the trial for reasons unrelated to OIT. The median tolerated dose increased from 30 mg (equivalent to approximately 1/8th of a peanut) to 3000 mg (12 peanuts) at the exit challenge, representing a 100-fold increase (p < 0.0001). OIT was associated with an improvement in QoL measures. Suppression of peanut skin prick test sizes and induction of peanut-specific IgG were observed in OIT but not in control participants.
Conclusions
Peanut OIT appears to be an efficacious treatment for adults with peanut allergy. Further studies are needed for confirmation and to characterize safety profiles in different adult subgroups.
Trial Registration
Grown Up Peanut Immunotherapy (GUPI) study; ClinicalTrials.gov identifier: NCT0364832
Time encoding via unlimited sampling: theory, algorithms and hardware validation
No full textAn alternative to conventional uniform sampling is that of time encoding, which converts continuous-time signals into streams of trigger times. This gives rise to Event-Driven Sampling (EDS) models. The data-driven nature of EDS acquisition is advantageous in terms of power consumption and time resolution and is inspired by the information representation in biological nervous systems. If an analog signal is outside a predefined dynamic range, then EDS generates a low density of trigger times, which in turn leads to recovery distortion due to aliasing. In this paper, inspired by the Unlimited Sensing Framework (USF), we propose a new EDS architecture that incorporates a modulo nonlinearity prior to acquisition that we refer to as the modulo EDS or MEDS. In MEDS, the modulo nonlinearity folds high dynamic range inputs into low dynamic range amplitudes, thus avoiding recovery distortion. In particular, we consider the asynchronous sigma-delta modulator (ASDM), previously used for low power analog-to-digital conversion. This novel MEDS based acquisition is enabled by a recent generalization of the modulo nonlinearity called modulo-hysteresis. We design a mathematically guaranteed recovery algorithm for bandlimited inputs based on a sampling rate criterion and provide reconstruction error bounds. We go beyond numerical experiments and also provide a first hardware validation of our approach, thus bridging the gap between theory and practice, while corroborating the conceptual underpinnings of our work
University College London (UCL) Public Policy - COP29 — How International Collaboration Can Advance Development Goals and Include Those Most Affected by Climate Change
No full textFresh from Baku, Marta Koch (UCL Population, Policy and Practice Research and Teaching Department) overviews the role that small island nation communities played in this year’s COP
Sprayed graphene-based coating enabling antifog and smart features
No full textLarge-area and low-cost coatings introducing electrical, optical, thermal, and surface control functionalities are highly demanded in the fields of flexible and wearable electronics for applications ranging from agrifood and smart packaging to electronic textiles and aerospace. Here, we report a graphene-based coating with combined antifog, electrical, and thermal functionalities suitable for spray deposition on commercially recyclable plastic substrates. A graphene ink formulation in a low-boiling-point solvent, stabilized by polyvinylpyrrolidone, enables compatibility with deposition processes in the coating industry. Spray-coated graphene films on polyethylene demonstrated antifog properties, achieving a 1.5-fold reduction in the contact angle at a 5% higher optical transmittance compared to commercial antifog coatings. Mechanical testing revealed more than a 1.8-fold improvement in Young’s modulus compared to the bare polyethylene. Moreover, by depositing another thin film of poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS) underneath the graphene coating, electrical conductivity (sheet resistance of about 330 Ω/sq) with similar transparency can be achieved. Testing of the thermal properties of the film demonstrated how these conductive coatings can be used as heaters, reaching about 50 °C at a 30 V bias. Moreover, the graphene smart antifog coating showed a 97% improvement in thermal conductivity, increasing to 283% for the graphene/PEDOT:PSS multilayer coating with respect to the PE. The integration of these combined and novel smart functionalities on commercial recyclable plastic widens the application arena of smart coatings beyond agrifood, toward packaging, automotive, and aerospace fields