A Compendium of Mutational Signatures of Environmental Agents.

Whole-genome-sequencing (WGS) of human tumors has revealed distinct mutation patterns that hint at the causative origins of cancer. We examined mutational signatures in 324 WGS human-induced pluripotent stem cells exposed to 79 known or suspected environmental carcinogens. Forty-one yielded characteristic substitution mutational signatures. Some were similar to signatures found in human tumors. Additionally, six agents produced double-substitution signatures and eight produced indel signatures. Investigating mutation asymmetries across genome topography revealed fully functional mismatch and transcription-coupled repair pathways. DNA damage induced by environmental mutagens can be resolved by disparate repair and/or replicative pathways, resulting in an assortment of signature outcomes even for a single agent. This compendium of experimentally induced mutational signatures permits further exploration of roles of environmental agents in cancer etiology and underscores how human stem cell DNA is directly vulnerable to environmental agents. VIDEO ABSTRACT.

Kimberlites reveal 2.5-billion-year evolution of a deep, isolated mantle reservoir.

The widely accepted paradigm of Earth's geochemical evolution states that the successive extraction of melts from the mantle over the past 4.5 billion years formed the continental crust, and produced at least one complementary melt-depleted reservoir that is now recognized as the upper-mantle source of mid-ocean-ridge basalts1. However, geochemical modelling and the occurrence of high 3He/4He (that is, primordial) signatures in some volcanic rocks suggest that volumes of relatively undifferentiated mantle may reside in deeper, isolated regions2. Some basalts from large igneous provinces may provide temporally restricted glimpses of the most primitive parts of the mantle3,4, but key questions regarding the longevity of such sources on planetary timescales-and whether any survive today-remain unresolved. Kimberlites, small-volume volcanic rocks that are the source of most diamonds, offer rare insights into aspects of the composition of the Earth's deep mantle. The radiogenic isotope ratios of kimberlites of different ages enable us to map the evolution of this domain through time. Here we show that globally distributed kimberlites originate from a single homogeneous reservoir with an isotopic composition that is indicative of a uniform and pristine mantle source, which evolved in isolation over at least 2.5 billion years of Earth history-to our knowledge, the only such reservoir that has been identified to date. Around 200 million years ago, extensive volumes of the same source were perturbed, probably as a result of contamination by exogenic material. The distribution of affected kimberlites suggests that this event may be related to subduction along the margin of the Pangaea supercontinent. These results reveal a long-lived and globally extensive mantle reservoir that underwent subsequent disruption, possibly heralding a marked change to large-scale mantle-mixing regimes. These processes may explain why uncontaminated primordial mantle is so difficult to identify in recent mantle-derived melts.

Optical and EPR Detection of a Triplet Ground State Phenyl Nitrenium Ion.

Nitrenium ions are important reactive intermediates participating in the synthetic chemistry and biological processes. Little is known about triplet phenyl nitrenium ions regarding their reactivity, lifetimes, spectroscopic features, and electronic configurations, and no ground state triplet nitrenium ion has been directly detected. In this work, m-pyrrolidinyl-phenyl hydrazine hydrochloride (1) is synthesized as the photoprecursor to photochemically generate the corresponding m-pyrrolidinyl-phenyl nitrenium ion (2), which is computed to adopt a π, π* triplet ground state. A combination of femtosecond (fs) and nanosecond (ns) transient absorption (TA) spectroscopy, cryogenic continuous-wave electronic paramagnetic resonance (CW-EPR) spectroscopy, computational analysis, and photoproduct studies was performed to elucidate the photolysis pathway of 1 and offers the first direct experimental detection of a ground state triplet phenyl nitrenium ion. Upon photoexcitation, 1 forms S1, where bond heterolysis occurs and the NH3 leaving group is extruded in 1.8 ps, generating a vibrationally hot, spin-conserving closed-shell singlet phenyl nitrenium ion (12) that undergoes vibrational cooling in 19 ps. Subsequent intersystem crossing takes place in 0.5 ns, yielding the ground state triplet phenyl nitrenium ion (32), with a lifetime of 0.8 µs. Unlike electrophilic singlet phenyl nitrenium ions, which react rapidly with nucleophiles, this triplet phenyl nitrenium reacts through sequential H atom abstractions, resulting in the eventual formation of the reduced m-pyrrolidinyl-aniline as the predominant stable photoproduct. Supporting the triplet ground state, continuous irradiation of 1 in a glassy matrix at 80 K in an EPR spectrometer forms a paramagnetic triplet species, consistent with a triplet nitrenium ion.

Sub-Band Assisted Z-Scheme for Effective Non-Sacrificial H2O2 Photosynthesis.

Photosynthesis of H2O2 from earth-abundant O2 and H2O molecules offers an eco-friendly route for solar-to-chemical conversion. The persistent challenge is to tune the photo-/thermo- dynamics of a photocatalyst toward efficient electron-hole separation while maintaining an effective driving force for charge transfer. Such a case is achieved here by way of a synergetic strategy of sub-band-assisted Z-Scheme for effective H2O2 photosynthesis via direct O2 reduction and H2O oxidation without a sacrificial agent. The optimized SnS2/g-C3N4 heterojunction shows a high reactivity of 623.0 µmol g-1 h-1 for H2O2 production under visible-light irradiation (λ > 400 nm) in pure water, ≈6 times higher than pristine g-C3N4 (100.5 µmol g-1 h-1). Photodynamic characterizations and theoretical calculations reveal that the enhanced photoactivity is due to a markedly promoted lifetime of trapped active electrons (204.9 ps in the sub-band and >2.0 ns in a shallow band) and highly improved O2 activation, as a result of the formation of a suitable sub-band and catalytic sites along with a low Gibbs-free energy for charge transfer. Moreover, the Z-Scheme heterojunction creates and sustains a large driving force for O2 and H2O conversion to high value-added H2O2.

Real-time millimeter wave holography with an arrayed detector.

Millimeter and terahertz wave imaging has emerged as a powerful tool for applications such as security screening, biomedical imaging, and material analysis. However, intensity images alone are often insufficient for detecting variations in the dielectric constant of a sample, and extraction of material properties without additional phase information requires extensive prior knowledge of the sample. Digital holography provides a means for intensity-only detectors to reconstruct both amplitude and phase images. Here we utilize a commercially available source and detector array, both operating at room temperature, to perform digital holography in real-time for the first time in the mm-wave band (at 290 GHz). We compare the off-axis and phase-shifting approaches to digital holography and discuss their trade-offs and practical challenges in this regime. Owing to the low pixel count, we find phase-shifting holography to be the most practical and high fidelity approach for such commercial mm-wave cameras even under real-time operational requirements.

Tissue Organoid Cultures Metabolize Dietary Carcinogens Proficiently and Are Effective Models for DNA Adduct Formation.

Human tissue three-dimensional (3D) organoid cultures have the potential to reproduce in vitro the physiological properties and cellular architecture of the organs from which they are derived. The ability of organoid cultures derived from human stomach, liver, kidney, and colon to metabolically activate three dietary carcinogens, aflatoxin B1 (AFB1), aristolochic acid I (AAI), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), was investigated. In each case, the response of a target tissue (liver for AFB1; kidney for AAI; colon for PhIP) was compared with that of a nontarget tissue (gastric). After treatment cell viabilities were measured, DNA damage response (DDR) was determined by Western blotting for p-p53, p21, p-CHK2, and γ-H2AX, and DNA adduct formation was quantified by mass spectrometry. Induction of the key xenobiotic-metabolizing enzymes (XMEs) CYP1A1, CYP1A2, CYP3A4, and NQO1 was assessed by qRT-PCR. We found that organoids from different tissues can activate AAI, AFB1, and PhIP. In some cases, this metabolic potential varied between tissues and between different cultures of the same tissue. Similarly, variations in the levels of expression of XMEs were observed. At comparable levels of cytotoxicity, organoids derived from tissues that are considered targets for these carcinogens had higher levels of adduct formation than a nontarget tissue.

Risk of Sleep Problems in Middle-Aged and Older Adults Experiencing Bodily Pains: Serial Multiple Mediation Estimates of Emotional Distress and Activity Limitations.

OBJECTIVES: Pain is increasingly becoming common among middle-aged and older adults. While research on the association between pain characteristics and sleep problems (SP) is limited in low- and middle-income countries, the underlying mechanisms of the association are poorly understood. This study examines the association of bodily pain intensity and pain interference with SP and investigates the mediating role of activity limitation and emotional distress in this association. METHODS: We analyzed population-based data, including 1,201 individuals aged ≥50 (mean [SD] age 66.14 [11.85] years) from the 2016-2018 AgeHeaPsyWel-HeaSeeB study in Ghana. Multiple OLS regressions and serial multiple mediation modeling using bootstrapping analyses examined direct and indirect effects from pain to SP through activity limitation and emotional distress. RESULTS: Regressions demonstrated that pain intensity and interference were significantly associated with higher levels of activity limitation, emotional distress, and SP (range: ß = 0.049-0.658). Bootstrapping analysis showed that activity limitation and emotional distress serially mediated the relationship between pain intensity and SP (total effect: ß = 0.264, Bootstrap 95% confidence interval [CI] = 0.165-0.362; direct effect: (ß = 0.107, Bootstrap 95% CI = 0.005-0.210; total indirect effect: ß = 0.156, Bootstrap 95% CI = 0.005-0.210) accounting for ∼59%. Activity limitation and emotional distress mediated pain interference and SP association (total effect: ß = 0.404, Bootstrap 95% CI = 0.318-0.490; direct effect: ß = 0.292, Bootstrap 95% CI = 0.201-0.384; and total indirect effect: ß = 0.112, Bootstrap 95% CI = 0.069-0.156) yielding ∼28%. CONCLUSION: Our data suggest that activity limitation and emotional distress may convey stress-related risks of pain on SP. Future research should evaluate if activity limitation and emotional distress could be effective targets to reduce the effect of pain on sleep in later-life.

Meeting the WHO Physical Activity Guidelines is Associated With Lower Odds of Depression in Older Adults: Potential Psychosomatic Mechanisms.

OBJECTIVES: Limited data exist on the association between physical activity (PA) and depression in older adults from low- and middle-income countries (LMICs). In this study, we examine the association between meeting the World Health Organization (WHO) PA guidelines and depression in adults aged ≥50 years in Ghana and investigate the psychosomatic factors explaining this association. METHODS: Cross-sectional data from the Aging, Health, Psychological Well-being, and Health-seeking Behavior Study in Ghana (2016-18) were analyzed. Depression was assessed with the Center for Epidemiological Studies Depression Scale (CES-D-10). PA was assessed using the International Physical Activity Questionnaire Short Form (IPAQ-SF). Multivariable logistic regression and Hayes PROCESS macro with bootstrapping mediation analyses were performed to evaluate the hypothesized associations. RESULTS: The study included 1201 individuals (mean [SD] age 66.1 [11.9] years; 63.3% women). The prevalence of meeting PA guidelines and depression was 36.7% and 29.5%, respectively. Meeting the WHO-recommended PA guidelines was associated with a 16% lower rate of developing depression even after adjusting for potential confounders (OR = 0.84, p <0.001). This association was much stronger among men and those aged 50-64 years. Loneliness, social isolation, sleep problems, functional limitations, and pain characteristics largely mediated the association of PA with depression. CONCLUSIONS: PA was negatively associated with depression among older adults in Ghana, and psychosocial and physical factors partially explained the association. The promotion of PA in old age may aid in the prevention of depression, especially in men and those aged 50-64 years. Longitudinal data may confirm our findings.

High-level reverse intersystem crossing of charge transfer compounds: to fluoresce or not to fluoresce?

Thermally activated delayed fluorescence (TADF) has been widely applied to electroluminescent materials to take the best advantage of triplet excitons. For some materials, the TADF originates from high-level reverse intersystem crossing (hRISC), and has attracted much attention due to its high efficiency for utilizing the triplet excitons. However, reports concerning the mechanistic studies on the hRISC-TADF process and structure-property correlation are sparse. In this study, we prepared three compounds containing triphenylamine and benzophenone with different substitution positions, o-TPA-BP, m-TPA-BP, and p-TPA-BP, in which only p-TPA-BP displays strong luminescence and hRISC-TADF features. To investigate the mechanism of the substituent-position-dependent hRISC-TADF, ultrafast time-resolved spectroscopy was utilized to observe the deactivation pathways with the assistance of theoretical calculations. The results show that o-TPA-BP will not generate triplet species, and the triplet species for m-TPA-BP will rapidly deactivate. Only p-TPA-BP can transition back to the singlet state from the T2 state effectively and exhibit a large gap between T1 and T2 to favor the hRISC route. These results illustrate how the substitution position affects the ISC and further influences the luminescence properties, which can provide new insights for developing new high-efficiency luminescent materials.

Later Life Food Insecurity and Social Isolation in Ghana: The Importance of Psychological Factors.

BACKGROUND: Social isolation (SI) and food insecurity (FI) are important social determinants of health that can negatively impact well-being in old age. While research on the association between FI and SI is limited in LMICs, the mediators of this association are largely unknown. This cross-sectional study examined whether FI is associated with SI among older adults in Ghana and whether psychological factors (i.e., depression, anxiety, and sleep problems) mediated the association. METHODS: Our study consisted of adults aged ≥50 years in the Aging, Health, Well-being, and Health-seeking Behavior Study. SI was assessed with the Berkman-Syme Social Network Index, while FI was assessed with dietary inadequacy-related items. We used an ordinary least squares regression (OLS), logistic regressions, and bootstrapping modeling approach to examine our hypotheses with p < 0.05. RESULTS: The analysis included 1201 individuals (Mage = 66 [SD = 12], women = 63%). In the full sample (ß = 0.21; p < 0.001) and in women (ß = 0.30, p < 0.001) but not in men, FI was independently associated with SI. FI was comparably associated with increases in SI for the 50-64 age group (ß = 0.21, p < 0.001) and ≥65 age cohort (ß = 0.19, p < 0.01). Moreover, FI showed differential associations with specific domains of SI (OR = 1.81 to 1.45, p < 0.001). Finally, the FI-SI association was mediated by depressive symptoms (65.16%), anxiety symptoms (30.16%), and sleep problems (9.50%). CONCLUSIONS: Our data highlight the fundamental role of FI in SI among older adults, and the effect is explained by psychosocial factors. Interventions targeted toward strengthening interpersonal ties in old age should include addressing FI and older adults' psychosocial outcomes.

Scaling up noncommunicable disease care in a resource-limited context: lessons learned and implications for policy.

BACKGROUND: Although primary care models for the care of common non-communicable diseases (NCD) have been developed in sub-Saharan Africa, few have described an integrated, decentralized approach at the community level. We report the results of a four-year, Ethiopian project to expand this model of NCD care to 15 primary hospitals and 45 health centres encompassing a wide geographical spread and serving a population of approximately 7.5 million people. METHODS: Following baseline assessment of the 60 sites, 30 master trainers were used to cascade train a total of 621 health workers in the diagnosis, management and health education of the major common NCDs identified in a scoping review (hypertension, diabetes, chronic respiratory disease and epilepsy). Pre- and post-training assessments and regular mentoring visits were carried out to assess progress and remedy supply or equipment and medicines shortages and establish reporting systems. The project was accompanied by a series of community engagement activities to raise awareness and improve health seeking behaviour. RESULTS: A total of 643,296 people were screened for hypertension and diabetes leading to a new diagnosis in 24,313 who were started on treatment. Significant numbers of new cases of respiratory disease (3,986) and epilepsy (1,925) were also started on treatment. Mortality rates were low except among patients with hypertension in the rural health centres where 311 (10.2%) died during the project. Loss to follow up (LTFU), defined as failure to attend clinic for > 6 months despite reminders, was low in the hospitals but represented a significant problem in the urban and rural health centres with up to 20 to 30% of patients with hypertension or diabetes absenting from treatment by the end of the project. Estimates of the population disease burden enrolled within the project, however, were disappointing; asthma (0.49%), hypertension (1.7%), epilepsy (3.3%) and diabetes (3.4%). CONCLUSION: This project demonstrates the feasibility of scaling up integrated NCD services in a variety of locations, with fairly modest costs and a methodology that is replicable and sustainable. However, the relatively small gain in the detection and treatment of common NCDs highlights the huge challenge in making NCD services available to all.

Transient Absorption Spectroscopic Investigation of the Photocyclization-Deprotection Reaction of 3',5'-Dimethoxybenzoin Fluoride.

The 3',5'-dimethoxybenzoin (DMB) system has been widely investigated as a photoremovable protecting group (PRPG) for the elimination of various functional groups and has been applied in many fields. The photolysis of DMB fluoride leads to a highly efficient photocyclization-deprotection reaction, resulting in a high yield of 3',5'-dimethoxybenzofuran (DMBF) in a MeCN solution, while there is a competitive reaction that produces DMB in an aqueous solution. The yield of DMB increased as the volume ratio of water increased. To understand the solvent effect of the photolysis of selected DMB-based compounds, a combination of femtosecond to nanosecond transient absorption spectroscopies (fs-TA and ns-TA), nanosecond time-resolved resonance Raman spectroscopy (ns-TR3) and quantum chemical calculation was employed to study the photophysical and photochemical reaction mechanisms of DMB fluoride in different solutions. Facilitated by the bichromophoric nature of DMB fluoride with electron-donating and -withdrawing chromophores, the cyclized intermediates could be found in a pure MeCN solution. The deprotection of a cyclic biradical intermediate results in the simultaneous formation of DMBF and a cyclic cation species. On the other hand, in aqueous solution, fs-TA experiments revealed that α-keto cations could be observed after excitation directly, which could easily produce the DMB through the addition of a hydroxyl within 8.7 ps. This work provides comprehensive photo-deactivation mechanisms of DMB fluoride in MeCN and aqueous conditions and provides critical insights regarding the biomedical application of DMB-based PRPG compounds.

Peptide/Nanoparticle Biointerfaces for Multistep Tandem Catalysis.

The realization of multifunctional nanoparticle systems is essential to achieve highly efficient catalytic materials for specific applications; however, their production remains quite challenging. They are typically achieved through the incorporation of multiple inorganic components; however, incorporation of functionality could also be achieved at the organic ligand layer. In this work, we demonstrate the generation of multifunctional nanoparticle catalysts using peptide-based ligands for tandem catalytic functionality. To this end, chimeric peptides were designed that incorporated a Au binding sequence and a catalytic sequence that can drive ester hydrolysis. Using this chimera, Au nanoparticles were prepared, which sufficiently presented the catalytic domain of the peptide to drive tandem catalytic processes occurring at the peptide ligand layer and the Au nanoparticle surface. This work represents unique pathways to achieve multifunctionality from nanoparticle systems tuned by both the inorganic and bio/organic components, which could be highly important for applications beyond catalysis, including theranostics, sensing, and energy technologies.

Two-Step Synthesis of B2 N2 -Doped Polycyclic Aromatic Hydrocarbon Containing Pentagonal and Heptagonal Rings with Long-Lived Delayed Fluorescence.

Pentagon-heptagon embedded polycyclic aromatic hydrocarbons (PAHs) have aroused increasing attention in recent years due to their unique physicochemical properties. Here, for the first time, this report demonstrates a facile method for the synthesis of a novel B2 N2 -doped PAH (BN-2) containing two pairs of pentagonal and heptagonal rings in only two steps. In the solid state of BN-2, two different conformations, including saddle-shaped and up-down geometries, are observed. Through a combined spectroscopic and calculation study, the excited-state dynamics of BN-2 is well-investigated in this current work. The resultant pentagon-heptagon embedded B2 N2 -doped BN-2 displays both prompt fluorescence and long-lived delayed fluorescence components at room temperature, with the triplet excited-state lifetime in the microsecond time region (τ = 19 µs). The triplet-triplet annihilation is assigned as the mechanism for the observed long-lived delayed fluorescence. Computational analyses attributed this observation to the small energy separation between the singlet and triplet excited states, facilitating the intersystem crossing (ISC) process which is further validated by the ultrafast spectroscopic measurements.

Surveillance of Mpox Cases Attending Sexual Health Services in England (SOMASS): design, implementation and initial findings from the SOMASS data collection tool, 2022.

OBJECTIVES: We aimed to design and implement a data collection tool to support the 2022 mpox (monkeypox) outbreak, and to describe clinical and epidemiological data from individuals with mpox attending sexual health services (SHSs) in England. METHODS: The UK Health Security Agency and the British Association for Sexual Health and HIV established the Surveillance of Mpox Cases Attending Sexual Health Services in England (SOMASS) system.Descriptive data were collected via a secure web-based data collection tool, completed by SHS clinicians following consultation with individuals with suspected mpox. Data were collected on patient demographics, clinical presentation and severity, exposures and behavioural characteristics. RESULTS: As of 17 November 2022, 276 SOMASS responses were submitted from 31 SHSs in England.Where recorded, most (245 of 261; 94%) individuals identified as gay, bisexual or men who have sex with men (GBMSM), of whom two-thirds were HIV negative (170 of 257; 66%) and taking HIV pre-exposure prophylaxis (87 of 140; 62%), with a median age of 37 years (IQR: 30-43). Where known, thirty-nine per cent (63 of 161) had a concurrent sexually transmitted infection (STI) at the time of their mpox diagnosis.For 46% of individuals (127 of 276), dermatological lesions were the initial symptom. Lesions were mostly asymmetrical and polymorphic, predominately affecting the genital area and perianal areas.Nine per cent (24 of 276) of individuals were hospitalised. We report an association between receptive anal intercourse among GBMSM and proctitis (27 of 115; 24% vs 7 of 130; 5%; p<0.0001), and the presence of perianal lesions as the primary lesion site (46 of 115; 40% vs 25 of 130; 19%; p=0.0003). CONCLUSIONS: We demonstrate multidisciplinary and responsive working to develop a robust data collection tool, which improved surveillance and strengthened the knowledge base. The SOMASS tool will allow data collection if mpox resurges in England. The model for developing the tool can be adapted to facilitate the preparedness and response to future STI outbreaks.

Insights into the Photodynamics of Fluorescence Emission and Singlet Oxygen Generation of Fluorogen Activating Protein-Malachite Green Systems.

The self-assembled fluorogen activating protein (FAP)-malachite green (MG) complex is a well-established protein-ligand system, which can realize binding-caused fluorescence turn-on of MG and singlet oxygen (1 O2 ) generation by MG iodination. To clarify the mechanism of fluorescence activation and 1 O2 generation, the photodynamics of different halogen-substituted MG derivatives and their corresponding FAP-MG complexes were studied by femtosecond transient absorption spectroscopy and theoretical computations. The results show that the rotation of MG is restricted by FAP binding, which prevents a rapid internal conversion to allow a longer lifetime for the excited MG to undergo fluorescence emission and intersystem crossing. Moreover, these FAP-MG complexes exhibit notably varied fluorescence quantum yields (ΦFL ) and 1 O2 yields. The study on the decay pathways indicates that such an anti-heavy atom effect predominately stems from the lifetimes of the excited-state species. The photodynamic mechanism study here will lead to more advanced FAP-MG systems with high spatiotemporal resolution.

Sleep and Happiness in Urban-Dwelling Older Adults in Ghana: A Serial Multiple Mediation Model of Generalized Anxiety and Depressive Symptoms.

OBJECTIVE: Sleep problems (SP) are highly prevalent and seriously affect health and well-being in old age. The aim of this study was to examine the association between SP and happiness in an urban-dwelling older sample. The authors further explore the effects of generalized anxiety and depressive symptoms in the SP-happiness link using serial mediating modeling. METHODS: Data came from the 2016 to 2018 Aging, Health, Psychological Well-being, and Health-seeking Behavior Study in Ghana (n = 661). The authors measured happiness with the cross-culturally validated item on a five-point scale. The GAD-7 and the CESD-8, respectively, assessed generalized anxiety and depressive symptoms. Participants reported nighttime and daytime SP in the last 30 days. The SPSS-based Hayes' PROCESS macro program (Model 6) was constructed to quantify the hypothesized mediation effect. RESULTS: The analysis included 661 adults aged greater than or equal to 50 years (mean age = 65.53 [SD] = 11.89 years; 65.20% women). After full adjustment, path models showed that SP was negatively associated with happiness (ß = -0.1277, 95%CI = -0.15950 to -0.096). Bootstrapping estimates revealed that the SP-happiness link was serially mediated via generalized anxiety representing 8.77%, depressive symptoms yielding 18.95%, and anxiety symptoms→depressive symptoms accounting for 26.70% of the total effect. CONCLUSION: Generalized anxiety and depressive symptoms may explain the negative association between SP and happiness in urban-dwelling older adults in the sub-Saharan African (SSA) context. Interventions, social and clinical, to improve happiness through sleep quality should include ways to improve mental health. Longitudinal and cross-cultural data are warranted to assess the bi-directionality of this relationship.

Time trends in ethnic inequalities in child health and nutrition: analysis of 59 low and middle-income countries.

BACKGROUND: Although ethnicity is a key social determinant of health, there are no global analyses aimed at identifying countries that succeeded in reducing ethnic gaps in child health and nutrition. METHODS: We identified 59 low and middle-income countries with at least two surveys since 2010 providing information on ethnicity or language and on three outcomes: under-five mortality, child stunting prevalence and a composite index (CCI) based on coverage with eight maternal and child health interventions. Firstly, we calculated population-weighted and unweighted measures of inequality among ethnic or language groups within each country. These included the mean difference from the overall national mean (absolute inequality), mean ratio relative to the overall mean (relative inequality), and the difference and ratio between the best- and worst-performing ethnic groups. Second, we examined annual changes in these measures in terms of annual absolute and relative changes. Thirdly, we compared trends for each of the three outcome indicators and identified exemplar countries with marked progress in reducing inequalities. RESULTS: For each outcome indicator, annual changes in summary measures tended to show moderate (Pearson correlation coefficients of 0.4 to 0.69) or strong correlations (0.7 or higher) among themselves, and we thus focused on four of the 12 measures: absolute and relative annual changes in mean differences and ratios from the overall national mean. On average, absolute ethnic or language group inequalities tended to decline slightly for the three outcomes, and relative inequality declined for stunting and CCI, but increased for mortality. Correlations for annual trends across the three outcomes were inconsistent, with several countries showing progress in terms of one outcome but not in others. Togo and Uganda showed with the most consistent progress in reducing inequality, whereas the worst performers were Nigeria, Moldova, Kyrgyzstan, Sao Tome and Principe, and Burkina Faso. CONCLUSIONS: Although measures of annual changes in ethnic or language group inequalities in child health were consistently correlated within each outcome, analyses of such inequalities should rely upon multiple measures. Countries showing progress in one child health outcome did not necessarily show improvements in the remaining outcomes. In-depth analyses at country level are needed to understand the drivers of success in reducing ethnic gaps.

Evaluation of the impact of assistive artificial intelligence on ultrasound scanning for regional anaesthesia.

BACKGROUND: Ultrasound-guided regional anaesthesia relies on the visualisation of key landmark, target, and safety structures on ultrasound. However, this can be challenging, particularly for inexperienced practitioners. Artificial intelligence (AI) is increasingly being applied to medical image interpretation, including ultrasound. In this exploratory study, we evaluated ultrasound scanning performance by non-experts in ultrasound-guided regional anaesthesia, with and without the use of an assistive AI device. METHODS: Twenty-one anaesthetists, all non-experts in ultrasound-guided regional anaesthesia, underwent a standardised teaching session in ultrasound scanning for six peripheral nerve blocks. All then performed a scan for each block; half of the scans were performed with AI assistance and half without. Experts assessed acquisition of the correct block view and correct identification of sono-anatomical structures on each view. Participants reported scan confidence, experts provided a global rating score of scan performance, and scans were timed. RESULTS: Experts assessed 126 ultrasound scans. Participants acquired the correct block view in 56/62 (90.3%) scans with the device compared with 47/62 (75.1%) without (P=0.031, two data points lost). Correct identification of sono-anatomical structures on the view was 188/212 (88.8%) with the device compared with 161/208 (77.4%) without (P=0.002). There was no significant overall difference in participant confidence, expert global performance score, or scan time. CONCLUSIONS: Use of an assistive AI device was associated with improved ultrasound image acquisition and interpretation. Such technology holds potential to augment performance of ultrasound scanning for regional anaesthesia by non-experts, potentially expanding patient access to these techniques. CLINICAL TRIAL REGISTRATION: NCT05156099.

Modelling the Encapsulation of 3-Hydroxyflavone with Cyclodextrin and Octa Acid and Comparing Their Differences.

The 3-hydroxyflavone (3-HF) is one of the common fluorescence probes. It has two distinct fluorescence bands: normal form and tautomer form. However, 3-hydroxyflavone has poor performance in water because of hydrogen bonding perturbation. The utilization of supramolecular chemistry would improve the fluorescence performance of 3-hydroxyflavone in water. In this paper, it reviews supramolecular chemistry of 3-hydroxyflavone with cyclodextrin and octa acid. Past research has found that the addition of ß-cyclodextrin to 3-hydroxyflavone in water would slightly improve the fluorescence intensity of the tautomer form. When adding γ-cyclodextrin to 3-hydroxyflavone in water, the green fluorescence intensity would be enhanced. Finally, the addition of octa acid creates a dry environment for the 3-hydroxyflavone, and it would only have a tautomer form. The ONIOM calculation shows the ways of self-assembly of ß- and γ-cyclodextrin. It can explain the difference in ratio between the tautomer form and normal form after understanding the interaction.