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The lives of women doctors in Britain, 1901-1939
No full textThis article examines the domestic lives of women doctors in Britain between 1901 and 1939. It offers a new perspective on the experiences of early professional women, about which we know little. My study examines 637 women, drawing primarily on individual data from the census and the 1939 Household Register. The article demonstrates that many of these women received vital support from relatives and friends throughout their careers. The attitudes of their fathers and husbands indicate that some middle-class men strongly encouraged women’s professional work. Nevertheless, women doctors faced sex discrimination within and beyond their profession. In this context, they established households designed to support their careers. These provide a valuable insight into the strategies that women professionals used to develop their careers while shouldering caring responsibilities, and into the relationships that helped women to expand their opportunities
A molecular phylogeny of the Nightjar Louse Fly Pseudolynchia garzettae (Rondani, 1979) (Diptera: Hippoboscidae) with a diagnostic morphological description of a sequenced specimen
No full textBackground: Cytochrome oxidase subunit I (COX1) DNA sequences are widely used as a means of identifying Eukaryotic species, but in some taxonomic groups, such as the louse flies (Diptera: Hippoboscidae), there are many species that have not been sequenced. Until very recently (Wawman, 2025), Pseudolynchia garzettae (Rondani, 1897) had no sequences in either of the two main databases, NCBI GenBank and International Barcode of Life v3 (BOLD), but there are multiple sequences identified only to the level of the genus Pseudolynchia.Methods: A Nightjar Louse Fly Pseudolynchia garzettae, was taken from an adult male European Nightjar Caprimulgus europaeus (Linnaeus, 1758), in Wales, United Kingdom, identified on the basis of its morphology and sequenced. The sequences were compared to all of the high-quality published COXI sequences for the genus Pseudolynchia.Results: A 662 base pair mitochondrial COX1 DNA sequence was obtained, confirming the sequenced fly as a separate species to all of the other sequenced specimens, which were all a single species Pseudolynchia canariensis (Macquart, 1839). A detailed morphological description of the fly and a differential diagnosis table is provided to aid researchers working with species in this genus.Conclusions: The DNA sequence supports the current taxonomy that places P. garzettae in the genus Pseudolynchia with P. canariensis, within the same clade as the genus Icosta
Biological individuality and fallacies of composition
Get PDFWithin the philosophy of biology, there is widespread acceptance of pluralism about biological individuality, according to which there are (at least) two theoretically important but distinct properties with a claim to the label ‘biological individuality’: evolutionary individuality and physiological individuality. Many who accept this also commit themselves—sometimes explicitly, often implicitly—to the further, surprising claim that the evolutionary individual and the physiological individual corresponding to a seemingly singular multicellular organism, such as a human being, are in fact distinct. I raise some problems for this distinctness claim, before developing a way of holding onto pluralism while rejecting this supposed consequence of it. I do so by uncovering some natural but hidden assumptions concerning the connections between certain evolutionarily significant properties of multicellular organisms and certain properties of their parts—assumptions which, once made explicit, can be seen to amount to fallacies of composition. I show that, by rejecting these assumptions, philosophers of biology can hold on to the appealing idea that familiar multicellular organisms are at once both evolutionary and physiological individuals
Combining adoptive T-cell therapy with cancer vaccines to enhance anti-tumour immune responses
No full textAdoptive T-cell therapy (ACT) consists of systemic infusion of cytotoxic tumour specific T cells aiming to control neoplasias. However, ACT still has very limited efficacy in humans. Cancer vaccines are promising immunotherapies to improve ACT, but the mechanisms underlying this combination are still poorly understood. To identify novel therapeutic approaches to improve ACT against solid tumours and to elucidate key factors responsible for immunotherapy efficacy, we have combined ACT with the chimpanzee adenovirus ChAdOx1 and poxvirus MVA vaccines encoding for specific tumour antigens. Strikingly, mice treated with the combination therapy showed a markedly higher tumour regression as compared to monotherapy controls. This efficacy was correlated with a superior tumour infiltration and expansion of tumour-reactive T cell populations in lymphoid organs. Surviving mice were rechallenged and monitored for 250 days and revealed that specific memory T cells populate lymph nodes, spleen and bone marrow. Interestingly, inflammation alone during ACT was sufficient to enhance T cell expansion and tumour control when followed by antigen-specific boosting. This synergy was abrogated when T cell trafficking to the lymph nodes was impaired. Importantly, we found that ChAdOx1 and MVA vaccination induces high levels of CXCL10. Crucially, blockade of its receptor, CXCR3, completely abrogated vaccine-mediated T cell expansion and tumour control. This suggests an essential role for CXCR3 signalling in the synergy between T-cell therapy and cancer vaccines. In conclusion, ChAdOx1 and MVA vaccination improves ACT against solid tumours by expanding transferred T cells that have long-lasting memory in a CXCR3-dependent manner
Data-driven performance guarantees for parametric optimization problems
Get PDFWe propose a data-driven method to establish probabilistic performance guarantees for parametric optimization problems solved via iterative algorithms. Our approach addresses two key challenges: providing convergence guarantees to characterize the worst-case number of iterations required to achieve a predefined tolerance, and upper bounding a performance metric after a fixed number of iterations. These guarantees are particularly useful for online optimization problems with limited computational time, where existing performance guarantees are often unavailable or unduly conservative. We formulate the convergence analysis problem as a scenario optimization program based on a finite set of sampled parameter instances. Leveraging tools from scenario optimization theory enables us to derive probabilistic guarantees on the number of iterations needed to meet a given tolerance level. Using recent advancements in scenario optimization, we further introduce a relaxation approach to trade the number of iterations against the risk of violating convergence criteria thresholds. Additionally, we analyze the trade-off between solution accuracy and time efficiency for fixed-iteration optimization problems by casting them into scenario optimization programs. Numerical simulations demonstrate the efficacy of our approach in providing reliable probabilistic convergence guarantees and evaluating the trade-off between solution accuracy and computational cost
Supervised rehabilitation versus self-managed rehabilitation for people with an acute first-time or recurrent patellar dislocation: the PRePPeD (Physiotherapy Rehabilitation Post Patellar Dislocation) external pilot randomised controlled trial and embedded qualitative study
No full textAims: To determine the feasibility of a full-scale randomised controlled trial (RCT) comparing two exercise-based rehabilitation interventions for people with an acute patellar dislocation.
Methods: A two-group external pilot RCT and embedded qualitative study conducted in five English National Health Service hospitals. Participants were aged ≥14 years with an acute (recruited ≤21 days of injury) first-time or recurrent patellar dislocation. Randomisation was 1:1 to supervised rehabilitation (4-6 physiotherapy sessions of tailored advice and prescribed home exercise) or self-managed rehabilitation (one physiotherapy session of advice, exercise instruction, and provision of materials to guide self-management). Quantitative feasibility objectives were 1.) patients’ willingness to be randomised, 2.) participant recruitment, 3.) intervention adherence (overall proportion of supervised rehabilitation participants that attended at least four physiotherapy sessions and self-managed rehabilitation participants that attended at least one session), and 4.) retention. Follow-up was three, six, and nine months after randomisation. There was no blinding. Semi-structured interviews aimed to understand participants’ experience of recovery, and the acceptability to them of the RCT interventions and follow-up methods.
Results: 50/88 (57%, 95% CI 46% to 67%) eligible patients were willing to be randomised. Sites recruited a mean of 1.4 (95% CI 0.6 to 1.8) participants per month, intervention adherence was 72% (95% CI 58% to 83%), and nine-month participant retention was 62% (95% CI 48% to 74%). During follow-up, three participants redislocated their patella and another underwent patellar stabilisation surgery. Interviews with nine pilot RCT participants found that the experience of recovery was conveyed through the themes ‘coming to terms with the initial injury’ and ‘regaining my former self’. Interviews also indicated that the RCT interventions and follow-up methods were generally acceptable to participants.
Conclusions: A full-scale RCT comparing two exercise-based rehabilitation interventions is feasible with minor modifications. Modifications should prioritise improving retention and participant attendance at physiotherapy sessions.
Registration: ISRCTN1423523
Collective asymmetric synthesis of the Strychnos alkaloids via thiophene S,S-dioxide cycloadditions
No full textThe Strychnos alkaloids have long been regarded as landmark targets for chemical synthesis due to their captivating architectures and notorious biological properties. However, the design of approaches that access multiple family members in an asymmetric, concise, and atom economical fashion remains a significant challenge. Here we show that thiophene S,S-dioxides (TDOs) offer a modular, rapid entry to the Strychnos natural products via inverse electron demand Diels-Alder cascades. Exceptional levels of stereocontrol are demonstrated in asymmetric TDO cycloadditions, which afforded tricyclic indolines of utility in medicinal chemistry research, and enabled stereoselective syntheses of eight Strychnos alkaloids by the shortest routes described to date, including the first synthesis of the iconic family member brucine. Using a machine-learning approach, computational studies provide insight into the source of stereoinduction, and reveal an intriguing and unexpected spontaneous cheletropic extrusion of SO2
Citizen deliberation and a communalist ethics of freedom
No full textUnlike many mainstream accounts of deliberation, Kwasi Wiredu offers a distinctly ethical conceptualization that foregrounds a robust accounting of pluralism in understanding the distinctive, general good of deliberation. Wiredu’s account partially emerges from his considerations of an African political geography where the pluralism of high ethnic stratification is structured into all political life. His broader arguments underscore the benefits to Africa and everywhere else of a robust consideration of pluralism and its ethical significance to deliberative understanding. Indeed, developing Wiredu’s arguments corrects a longstanding oversight in much deliberative theory which fails to treat pluralism robustly. Consequently, much mainstream theory misses a crucial, ethical, understanding of deliberation and its distinctive good. Developing Wiredu’s political and moral arguments, the article argues that deliberation fulfils a distinctly ethical function in enabling citizens’ moral consideration of each other and of those interests that are most meaningful to them in ways that are fundamental to the communal fabric of free society. This challenges the dominant justificatory view that sees deliberation predominantly as a means of justifying law and policy. By drawing out the moral and philosophical implications of Wiredu’s arguments, the article argues that the justificatory view fails to account for a normatively coherent understanding of deliberation because it fails, also, at an ethically robust understanding of the kind of difference—and agreement—with which deliberation is concerned. Further, with a field experiment, the article demonstrates that the empirical claim embedded in the justificatory view about the adherence of participants to deliberative decisions lacks support
ELIP: enhanced visual-language foundation models for image retrieval
Get PDFThe objective in this paper is to improve the performance of text-to-image retrieval. To this end, we introduce a new framework that can boost the performance of large-scale pre-trained vision-language models, so that they can be used for text-to-image re-ranking. The approach, Enhanced LanguageImage Pre-training (ELIP), uses the text query, via a simple MLP mapping network, to predict a set of visual prompts to condition the ViT image encoding. ELIP can easily be applied to the commonly used CLIP, SigLIP and BLIP-2 networks. On the evaluation side, we set up two new out-of-distribution (OOD) benchmarks, Occluded COCO and ImageNet-R, to assess the zeroshot generalisation of the models to different domains. The results demonstrate that ELIP significantly boosts CLIP/SigLIP/SigLIP2 text-to-image retrieval performance and outperforms BLIP-2 on several benchmarks, as well as providing an easy means to adapt to OOD datasets