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Iron tris-mesityl: a homoleptic iron( ii ) ferrate species for directed C–H activation
Full text linkC–H activation is a vital synthetic tool due to its superior atom economy and improved step efficiency making it amendable to late-stage functionalisation. In recent years iron has been gaining traction within this field due to its high abundance, low cost and low toxicity. Iron(0) phosphines for C–H activation via oxidative addition are well documented, however, only a handful of iron(ii) complexes competent at C–H activation via ligand-to-ligand hydrogen atom transfer (LLHT) or σ-bond metathesis have been identified. Herein we report the first homoleptic iron species capable of facilitating C–H activation, introducing a new class of well-defined iron(ii) complexes for this purpose, and detail the synthesis and characterisation of a range of tris-cyclometalated iron complexes using a variety of pyridine derived substrates. Density functional theory (DFT) calculations reveal that the C–H activation proceeds through a σ-bond metathesis pathway
Leadership strategies to foster innovation in healthcare organizations of the UK: a systematic review
Full text linkBackground: UK healthcare organizations face increasing pressure to innovate in response to technological advancements, resource constraints, and evolving patient expectations. Leadership plays a crucial role in driving such innovation by influencing organizational culture, employee engagement, and the adoption of new practices. Objectives: The main objective of this systematic review was to assess the most effective leadership strategies for fostering innovation within the UK healthcare sector. Methodology: A systematic search was conducted using databases such as Scopus, EBSCO, PubMed, and Google Scholar, with search terms focused on leadership, innovation, and healthcare. The PICO framework guided study selection, and inclusion criteria limited studies to those published between 2015 and 2024 in English and within the UK context. Ten studies met the criteria and were critically appraised using the CASP checklist. Results: This review found that transformational leadership was the most effective strategy for promoting innovation, followed by servant and transactional leadership. Transformational leadership enabled vision-sharing, employee empowerment, and cultural change, while servant leadership fostered autonomy and motivation. Transactional leadership supported operational efficiency and accountability. Organizational culture emerged as a key mediating factor, and leadership theories such as Contingency Theory and the Great Man Theory provided additional explanatory value. Conclusion: The review concludes that transformational leadership is best suited for encouraging innovation in UK healthcare, and recommends expanding future research to include larger sample sizes and cross-country comparisons to enhance generalizability
“ Poverty is a social issue, not a mathematical problem ”: examining the lessons for beneficiary identification from implementation of the UHC indigent program in Kenya
Full text linkBackground: Kenya rolled out a UHC indigent program aimed to expand financial protection and health service access for poor households through subsidized health insurance under the national insurer, National Health Insurance Fund (NHIF). As Kenya transitions to a new social health insurance framework under the Social Health Authority (SHA), understanding the implementation experience of the UHC indigent program is critical for informing the roll out of SHA’s indigent program. Methods: We conducted a qualitative process evaluation of the UHC indigent program using document reviews, semi-structured interviews with 23 key informants from national and county health authorities, development partners, and implementing actors, complemented by a validation workshop with 57 stakeholders. Our analysis was guided by Moore et al.‘s process evaluation framework and Wu et al.‘s policy capacity lens, examining implementation fidelity and capacities at multiple levels. Results: The program’s implementation deviated from its original centralized design, with counties exerting control over beneficiary identification due to national data gaps, incomplete rollout of the Harmonized Testing Tool, and political and operational constraints. Variations in targeting methods, reliance on under-resourced community health actors, and delays in biometric registration contributed to partial enrolment, limited access, exclusion errors, and mistrust. Although some counties reported increased service utilization, this was limited by unregistered dependents and lack of beneficiary awareness. Stakeholders expressed concern over SHA’s use of proxy means testing for identifying the poor, citing risks of exclusion, manipulation, and failure to capture locally constructed definitions of poverty. Conclusion: Kenya’s experience demostrates the need to align national targeting frameworks with local realities, invest in policy capacity across stakeholders, and prioritize community validation and communication in subsidy programs. As SHA rolls out a new indigent program, these lessons offer critical guidance for enhancing fidelity, equity, and accountability
Folate and global health umbrella review series, part 1: methodological framework and syntheses on anaemia and neural tube defects
Full text linkBackgroundFolate is essential for normal growth and in human health throughout the lifecycle. Clinical deficiency of folate impairs DNA synthesis and results in megaloblastic anaemia, while suboptimal folate status before and in early pregnancy results in an elevated risk of neural tube defects (NTD). The evidence on the association of folate status with other health outcomes is largely fragmented and understudied. We conducted a series of umbrella reviews examining the association between folate and multiple health outcomes in various populations and settings.MethodsWe searched MEDLINE, Embase, CINAHL, the Cochrane Library, and DARE from inception to February 2024 for systematic reviews with or without meta-analyses examining an association between folate intake/status and any health outcome. We performed screening and data extraction in duplicate and assessed the risk of bias using the ROBIS tool. Evidence was then characterised into unique associations (unique exposure measure - unique outcome measure - unique setting). For each category of unique associations, we identified the evidence based on the statistical power, recency of publication and the potential risk of bias. All unique associations were evaluated for credibility using predefined criteria.ResultsWe retrieved 3565 records and included 283 in the final synthesis. The evidence on anaemia consisted of four intervention trials demonstrating effectiveness of folic acid supplementation during pregnancy in reducing the risk of megaloblastic anaemia (relative risk (RR) = 0.21; 95% CI = 0.11, 0.38; I2 = 15%). Maternal folic acid use was also significantly inversely related to the prevention of NTD at birth (RR = 0.31; 95% CI = 0.16, 0.60; I2 = 0%) and NTD recurrence (RR = 0.30; 95% CI = 0.14, 0.65; I2 = 0%). This relationship was supported by the inverse association reported between low maternal blood folate concentrations and the increased risk of NTD. Further evidence showed that fortification of food with folic acid was associated with the lower prevalence of NTD on a population-level.ConclusionIn NTDs and anaemia, we identified strong evidence supporting the protective role of folate status based on intervention trials and observational studies. More recent reviews examining the role of folate in other less well understood health conditions will be presented in the subsequent reports.RegistrationPROSPERO: CRD42021265041
Germline duplication of MYCN predisposes to childhood embryonal tumours
Full text linkBackgroundNeuroblastoma and Wilms tumour (WT) are common childhood embryonal malignancies. Germline 2p24 duplication has been reported in several cases of neuroblastoma and WT, either as part of a larger 2p duplication or as a microduplication involving just 2p24.3. Although the larger duplications involve many genes, including ALK, the microduplications have been localised to a region including MYCN and DDX1.MethodsWe analysed Whole Genome Sequence data from adults and children sequenced for various indications. We utilised a workflow to extract structural and copy number variants, filtered to include duplications or gains of 2 kb-20 Mb, including these loci, followed by manual inspection in IGV. Associations were assessed using Fisher's exact test. Penetrance was estimated by Bayesian calculation of the conditional probability of disease.FindingsAmong 113,431 genomes, there were 6 participants with a microduplication that included the MYCN locus. Of these, two had a diagnosis of WT and one of neuroblastoma. The 2p24.3 microduplication was therefore identified in 3/197 with a definite history of WT/neuroblastoma and 3/113,234 without such a history (p < 0.0001). Penetrance is estimated to be 13%. Twelve participants were identified with a 2p24.3 microduplication that included the DDX1 locus but not MYCN, none of whom received a diagnosis of a childhood embryonal tumour.InterpretationWe have shown that 2p24.3 microduplications that include MYCN predispose to childhood embryonal tumours and should be routinely assessed when WT or neuroblastoma predisposition is suspected. We have also shown that there does not appear to be any increased incidence of childhood tumours when DDX1 alone is duplicated.FundingUCL Great Ormond Street Institute of Child Health Child Health Research CIO PhD Studentship, Brain Tumour Charity, Children with Cancer UK, Great Ormond Street Hospital Children's Charity, Olivia Hodson Cancer Fund, Cancer Research UK and the National Institute for Health Research
Evelyn Waugh: travel writing and politics
Full text linkIn 1936, when deployed as the Daily Mail’s correspondent in the Second Italo-Abyssinian War (1935-36), Evelyn Waugh came to realise what previously had seemed a joke: that travel, and travel writing, was deadly politically serious. The purpose of this thesis is to execute a similar move: to take Waugh’s political travel writing seriously. In particular, to investigate how his travel writing is guided by a commitment to a form of political Roman Catholicism, which he shared with a coterie of influential right-wing Catholic writers and thinkers in the 1930s. Furthermore, this thesis examines the long afterlife of Waugh’s 1930s travel writing in a post-war British political landscape that was hostile to his politico-religious ideas. Chapters One and Two of this thesis concern Waugh’s travel writing from the Second Italo-Abyssinian War. They examine the influence of Hilaire Belloc on Waugh’s interpretation of Italian Fascist expansionism as the rebirth of the Roman Empire, and argue that Waugh’s travel writing and journalism of this period forms part of the corpus of writing produced by English Catholic propaganda for Italy’s Roman Catholic imperialism in East Africa. Chapter Three analyses Waugh’s travel writing about Cárdenas’ Mexico in 1939. It argues that, by travelling to Mexico, Waugh constructs a travel book that indirectly addresses the Spanish Civil War. Chapter Four provides a reading of The Ordeal of Gilbert Pinfold (1957), which argues that it represents a form of experimental travel book addressing the long-lasting outcomes of Waugh’s 1930 political travel books. Chapter Five concerns Waugh’s return to Africa in 1959 where the continent was on the verge of decolonisation. It analyses Waugh’s response to what he perceived to be the failure of his politico-religious hopes for Africa in the 1930s, and his pessimism for European civilisation as a result. In summary, this thesis illuminates Waugh’s travel writing through an examination of the politico-religious argument that he advances between the 1930s and the 1960s
Novel remote sensing of electromagnetic properties
Full text linkElectromagnetic sensing plays a crucial role in modern technology, enabling contactless detection and monitoring across fields as diverse as medical diagnostics, industrial inspection, security systems, and materials testing. Among the various approaches, inductive sensing stands out for its simplicity, passive nature, and sensitivity to material properties such as conductivity and permeability. While widely used in applications like metal detection or imaging through eddy currents, the fundamental mechanisms that govern these interactions are still not fully understood - particularly when it comes to mapping electromagnetic property variations or localising objects with high spatial accuracy. This thesis explores how changes in the self-inductance of a resonant element can be exploited to characterise unknown materials and localise conductive objects. It begins with introducing a detailed analytical model describing the behaviour of a single split-ring resonator (SRR) placed near a sample. An analytical method is developed that allows the extraction of electromagnetic properties of materials - specifically, conductivity and permeability - from the shifts in resonant frequency and quality factor caused by the presence of the sample. The model accounts for skin depth effects and probe geometry and is validated both by numerical simulations and experimental results. The method was used to detect low-conductivity saline solutions with a tolerance of 5.5%, and was further tested in a biomedical setting using a 3D simulation of a human torso. Here, changes in lung conductivity caused by fluid accumulation (as might occur in pneumonia or COVID-19) produced measurable shifts in the resonator's response, supporting the potential for low-cost, non-invasive lung monitoring systems based on a single coil. The second half of the thesis focuses on localisation using magneto-inductive arrays - structured surfaces made of resonant cells coupled to one another. The presence of a conductive object alters the array's local properties, disrupting wave propagation and producing reflections that can be traced back to the object’s location. In a one-dimensional waveguide, both time-domain and frequency-domain reflectometry were used to localise a metallic object. Both methods were aided by the use of a machine learning algorithm, which mapped the changes in the time and frequency domain to object locations with an accuracy exceeding 90%, when objects were placed up to 15 mm above the array. Most notably, the time-domain reflectometry approach achieved error-free localisation up to 12 mm above the array and proved to be a more successful approach when localising objects on one-dimensional arrays. On the other hand, frequency-domain reflectometry proved to be a versatile method which was easily extended to two-dimensional arrays. A neural network was used to localise multiple objects with over 98% accuracy and distinguish between them with 97% confidence. A finger phantom was also successfully tracked, highlighting the potential for smart touch interfaces and human–machine interaction. Together, these studies demonstrate the versatility of magneto-inductive sensing - from characterising subtle changes in material properties to enabling precise object tracking on structured surfaces. The goal of this thesis is to advance our understanding of how resonant elements and their mutual interactions can be harnessed to develop sensitive, low-cost, and scalable sensing systems for real-world applications
Applied Bayesian inference for diachronic meaning change
Full text linkAs a language evolves, the meanings or senses of many words in the language change. Examples include "gay", whose predominant sense has changed from bright or cheerful to homosexual; and "mouse", which has acquired a new sense of a computer pointing device in addition to the rodent sense. Modelling words with multiple senses, and learning their diachronic meaning changes from unlabelled text, is a fascinating challenge in statistical inference. One way to approach the problem is through a class of generative Bayesian models derived from the topic modelling literature. In this framework, the sense of a target word is represented as a distribution over context words, and sense prevalence is represented as a distribution over senses, both of which may change with time. This thesis works within this framework to posit new models, model-fitting procedures and inference methods for unsupervised learning of word senses and measurement of diachronic meaning change. Quantifying inferential uncertainty is a particular focus, since this aspect is important for modelling the small and sparse datasets used in our main application. Significant gains are achieved in terms of predictive accuracy, ground-truth recovery, sampling efficiency and scalability. An intuitive method for selecting the learning rate in a generalised Bayes' posterior is also explored. All results are demonstrated on real data from ancient Greek and English, as well as simulated examples
Metabolomic profile of genetic liability to type 2 diabetes among 125,000 Mexican adults: a Mendelian randomisation study
No full textObjective: The Mexican population experiences a notably high prevalence of type 2 diabetes (T2D) and high T2D-associated disease risks. We used targeted plasma NMR-metabolomics data within a Mendelian randomisation framework to characterise the metabolomic profile of genetically-predicted liability to T2D in this population.Research Design and Methods: Between 1998 and 2004, 50,000 men and 100,000 women ≥35 years were recruited from Mexico City. Mendelian randomisation analyses used a genetic risk score (GRS) comprising 1055 established T2D-associated risk variants and eight pathway-specific T2D GRSs constructed from non-overlapping subsets of these variants to estimate associations with 143 metabolic biomarkers (including lipids, lipoproteins, fatty acids, amino acids, ketone bodies and other low molecular weight biomarkers).Results: Among 125,587 included participants, the T2D GRS explained 6.0% of T2D liability and was not associated with major potential confounders of the relationships of T2D with the circulating metabolome. Genetically-predicted liability to T2D was strongly positively associated with concentrations of VLDL particles and lipids within these, with triglycerides, branch chain amino acids and glycoprotein acetyls, and more modestly positively associated with IDL and LDL, particularly small LDL, particles. Inverse associations were found with relative concentrations of several fatty acids. Pathway-specific T2D GRSs all associated with higher T2D risk but showed differential relationships with circulating metabolic biomarkers.Conclusions: T2D is associated with widespread changes in the circulating metabolome among adults in Mexico reflecting diverse biological mechanisms and highlighting the importance of effective T2D management, including control of T2Dassociated dyslipidaemia, in this population
Effects of parental death on labor market outcomes
Full text linkNearly everyone experiences the death of a parent in adulthood, but little is known about its effects on adult children’s labor market outcomes and the underlying mechanisms. In this paper, we use Danish administrative data to examine the impact of parental loss on individual labor market outcomes. We leverage the timing of sudden, first parental deaths and adopt a matched-control difference-in-differences strategy. Our findings show that parental death negatively affects adult children’s earnings: sons’ earnings decline by 2% five years after parental loss, while daughters’ earnings decrease by 3% during the same period. Exploring the underlying mechanisms, we find that both men’s and women’s mental health deteriorates following parental loss: women seek psychological assistance more frequently, while both men and women increase their use of mental health and opioid prescriptions. Furthermore, women with young children experience a comparatively larger earnings decline (around 4%) likely due to the loss of informal childcare. These findings collectively highlight a substantial labor market penalty for individuals who experience parental death