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How can we promote academic GP careers? A qualitative framework analysis of factors affecting the development of the academic GP workforce
Get PDFObjectives General practice continues to be an under-represented career choice among medical school graduates, and the retention of the general practitioner (GP) workforce remains challenging. Academic general practice (AGP) is vital to the development of the evidence base for general practice and the education of the next generation of doctors and GPs. Academic careers and portfolio careers in general practice are seen as a means of increasing retention of GPs in the profession. However, AGP remains largely invisible to many and the number of AGPs is declining. There is no clear understanding of the reasons for this. The aim of this study was to explore factors that inhibit and promote AGP careers. Design Secondary framework analysis of data from two qualitative studies. Participants, setting and measures 41 GPs, GP trainees and Academic GPs (25 females and 16 males) across Scotland. Analysis of the data employed a framework based on Feldman and Ng’s model of the factors influencing career mobility, embeddedness and success in order to explore the barriers and enablers to GPs developing academic careers that exist at multiple levels from the personal to the structural. Results GPs encountered barriers to entering AGP at multiple levels. Lack of clarity and visibility of training pathways, including the lack of clear routes into academia at multiple career stages, were significant barriers, as were the effects of taking on academic work on overstretched practices, and relative job insecurity and lower pay in academic careers. Conclusion The findings of this research demonstrate that unless the structural issues affecting the profession more generally are addressed, significant barriers to pursuing AGP careers will remain.Peer reviewe
Kantian subjects : an analysis of the fundamental logical structure of the categorical imperative and the equivalence of its formulations
No full textThis thesis offers a detailed and critical interpretation of Immanuel Kant’s categorical imperative and its multiple formulations. Its aim is to highlight some of the problems that arise from treating the formulations as being extensionally equivalent with each other. At the same time, it also looks to provide an original interpretation in which some formulations refer to different subjects, namely, they operate at a different level of abstraction with regard to rational agency. While they are all expressions of the same principle, not all are extensionally equivalent because they consider the ontology of the rational agent from different standpoints.
The work first explains how the categorical imperative lies as the ultimate condition of possibility of the summum bonum in Kant’s moral theory. It then presents the significant lack of consensus among scholars regarding how the categorical imperative and its formulations operate and relate to one another. This work then analyses Hegel’s critique of the categorical imperative to show the difficulties of having the Fundamental Law of Pure Practical Reason in the Critique of Practical Reason be equivalent to those in the Groundwork of the Metaphysics of Morals, especially the formulation that is known as the Formula of Universal Law. Finally, this work proposes that the different formulations pertain to distinct levels of abstraction or subjects, which is evidenced among other things by the different behavior of the formulations due to the differences of their conceptual structures, which reflect the underlying differences in the analysis of the ontology of rational agency."This work was supported by Agencia Nacional de Investigacio n y Desarrollo (ANID) of the Chilean Government (project number 21210998); and The Vicerrectorí a Academica de Investigacio n of Pontificia Universidad Catolica de Chile."--Fundin
A viral SAVED protein with ring nuclease activity degrades the CRISPR second messenger cA4
Get PDFFunding: This work was supported by a European Research Council Advanced Grant (Grant REF 101018608 to MFW).Type III CRISPR systems typically generate cyclic oligoadenylate second messengers such as cyclic tetra-adenylate (cA4) on detection of foreign RNA. These activate ancillary effector proteins which elicit a diverse range of immune responses. The Calp (CRISPR associated Lon protease) system elicits a transcriptional response to infection when CalpL (Calp Lon protease) binds cA4 in its SAVED (SMODS associated and fused to various effectors domain) sensor domain, resulting in filament formation and activation of the Lon protease domain, which cleaves the anti-Sigma factor CalpT, releasing the CalpS (Calp Sigma factor) for transcriptional remodelling. Here, we show that thermophilic viruses have appropriated the SAVED domain of CalpL as an anti-CRISPR, AcrIII-2 (second anti-CRISPR of type III systems), which they use to degrade cA4. AcrIII-2 dimers sandwich cA4, degrading it in a shared active site to short linear products, using a mechanism highly reminiscent of CalpL. This results in inhibition of a range of cA4 activated effectors in vitro. This is the first example of a virally encoded SAVED domain with ring nuclease activity, highlighting the complex interplay between viruses and cellular defences.Peer reviewe
Light sheet microscopy and spectroscopy of whispering gallery mode microlaser particles
Get PDFWhispering gallery mode microlasers are a recently developed sensing tool which can be used to make localised measurements of refractive index changes in a biological tissue through examination of their emission spectrum. This allows the direct quantification of various mechanical or physical properties in microscopic organisms. Recently these microlasers have found applications in studies in range of sample types including in vitro samples such as individual cells or three-dimensional multicellular spheroids as well as in vivo samples such as zebrafish embryos and larval fruit flies. These studies have typically made use of standard brightfield illumination and fluorescence microscopes with a coupled spectrometer to perform measurements. However, for detailed studies of large 3D tissues displaying a large degree of structural heterogeneity it is essential to employ more advanced microscopy techniques to allow full 3D imaging of the sample with high resolution. To this end some studies have performed confocal microscopy to acquire 3D images of samples with combined microlaser spectroscopy. Confocal microscopy has limitations however, with its point scanning illumination style having limited temporal resolution as well as causing sample degradation due to phototoxicity effects. To mitigate this one can an implement light sheet microscopy which makes use of a line-based illumination geometry to allow whole planes of a sample to be imaged in one acquisition whilst minimising phototoxic effects. In this thesis, a dual modality system consisting of a light sheet fluorescence microscope coupled to a spectrometer for use in microlaser studies is designed and built allowing implementation of combined high-resolution imaging and microlaser spectral analysis. After construction, the effect of the light sheet illumination of the microlasers is examined with regards to the coupling behaviour between the sheet and the microlaser. The performance of the system is demonstrated through measurements of the absolute refractive index using microlasers inserted into an agarose sample and in fixed zebrafish tail muscle tissue. Finally, the muscles of fruit fly larva samples are imaged in vivo using the light sheet system and the prospect of using these samples for cardiology studies is discussed
Sexual selection in wild populations of seed bugs : the role of size in pre-copulatory mate choice by females and males
Get PDFFunding: This work was supported by the Natural Environmental Research Council via an IAPETUS2 PhD studentship held by Ophelia S Fritsch (grant reference NE/S007431/1).Although sexual selection is a well-established part of evolutionary biology, controversies remain about the roles of males and females. For instance, despite clear evidence of male mate choice across a very broad range of species, traditional views of male and female sex roles—the former competitive, the latter choosy—are still common. In addition, studies looking at mate choice in natural populations, especially in terms of male mate choice, remain limited. Here, we consider body size, an important phenotype in mate choice in many species, and its association with patterns of non-random mating in wild populations of two species of seed bugs, Spilostethus pandurus and Lygaeus creticus. We found strong directional pre-copulatory sexual selection for larger females in both species. On the other hand, patterns of selection on male size differed between the two species. There was directional sexual selection for larger individuals in L. creticus, and stabilizing selection for intermediate-sized males in S. pandurus. Our results suggest that while males and females in both species mate non-randomly with respect to the body size of their partner, male pre-copulatory mate choice may be an important component of selection on females in the wild.Peer reviewe
Enantiocontrol in radical coupling reactions : a catalytic [1,2]-rearrangement of allylic ammonium ylides
Get PDFFunding: A.D.S. and K.K. thank the EPSRC Programme Grant “Boron: Beyond the Reagent” (EP/W007517) for support.The [1,2]-rearrangement of ammonium ylides is a fascinating reaction that has captivated the mechanistically inclined for almost a century. Allylic migration of these ylides is dominated by a thermally allowed concerted [2,3]-rearrangement, with the [1,2]-process usually absent or a minor pathway. As such, development of a [1,2]-selective reaction within allylic systems is an uphill battle. Decades of mechanistic insights have not settled the debate on the true pathway for [1,2]-rearrangement, with a C–N homolysis step followed by a radical coupling within a solvent cage commonly accepted. Herein, we describe our journey through the development of such a process and opine on the broader context in which this chemistry may currently rest.Peer reviewe
Quantum-enhanced protocols : secure quantum state sharing and noisy field estimation
Get PDFThe first part of this thesis presents a new quantum state sharing scheme that distributes the quantum information contained within a quantum state across three shares such that it cannot be accessed from any individual share. By combining any two shares, however, the original state can be reconstructed. This requirement for collaboration ensures security against single dishonest actors. We demonstrate that the protocol is provably secure for the class of pure Gaussian states and is effective for the sharing of mixed states, although security for those cannot be guaranteed.
We then go on to discuss the use of quantum state sharing as a hybrid protocol for the distribution of discrete-variable states, including Fock states and particle-number qubits, using Gaussian entanglement. We demonstrate that, with access to suitable entanglement resources, this can be achieved with arbitrarily-high fidelity and that the security of the protocol can be guaranteed for qubit-like states.
In the second part of this thesis, we consider the potential for quantum entanglement to improve the measurement of gradients in the magnetic field. We find that in the absence of noise, it is optimal to measure orthogonal gradients individually, devoting the full measurement network to the measurement of a single gradient at a time. In the presence of high levels of environment noise, however, it becomes preferable to measure them simultaneously. We find the optimal network configurations and entanglement structures to make these measurements in the presence of three common noise sources."This work was supported by funding from the University of St Andrews (St Leonard’s College and School of Physics and Astronomy), and from the International Macquarie University Research Excellence Scholarship scheme."--Fundin
Functional and evolutionary synergy of trait components can explain the existence of leaf masquerade in katydids
Get PDFFunding: J.B.W. was supported by an 1851 Royal Commission for the Exhibition Research Fellowship, C.E.J.R. by the University of St Andrews’ Rector’s Scholarship, and N.W.B. by the UK Natural Environment Research Council (NE/W001616/1).One of the most enduring mysteries in biology concerns the evolution of complex adaptations made up of interacting component traits. When these component traits do not enhance fitness independently of one another, their origin requires that they evolve sequentially through intermediate steps that do not produce their full adaptive value as a combined trait, or alternatively, that they arise via simultaneous, synergistic evolution. We tested these alternatives using the powerful but accessible example of leaf masquerade in katydids, where in some species, highly modified wings strikingly mimic vegetation to avoid predator recognition. Combining a field predation experiment with a phylogenetic comparative analysis of wing morphology in 58 Neotropical katydid species, we show that color and shape synergistically interact to enhance survival in the wild, and modifications in both traits evolved concurrently during diversification of this clade. Our findings identify the adaptive value of masquerade camouflage in the wild and show how concordant evolutionary change in separate traits—evolutionary synergy—can generate extraordinarily specialized, multi-component adaptations.Peer reviewe
Long-term cycling stability of sodium/sodium ion cells probed by in situ solid-state NMR spectroscopy
Get PDFFunding: T.G. acknowledges the DFG under contract GU-1650/3-2 project number 429632542 for financial support.Sodium-ion batteries are at the forefront of new, sustainable energy systems required for the global energy transition. 23Na in situ solid-state nuclear magnetic resonance spectroscopy is capable of unraveling structures in working electrochemical cells during the charging and discharging processes. To evaluate its suitability for long-term studies, local sodium environments in sodium/sodium ion cells based on silicon carbonitride and hard carbon materials are tracked for up to 49 cycles (228.5 h). The formation of dendrites as well as the decay of a secondary metallic sodium species is observed, and local structures are analyzed up to the point of capacity degradation and cell failure. Initial points of cell breakdown are reflected in the NMR data by characteristic changes in signal intensities, whereas the degradation of the cells is reflected by a cease to periodic signal intensity fluctuations. Meanwhile, ex situ 23Na NMR spectra of the deactivated cells reveal a complex range of environments for sodium ions.Peer reviewe
Precipitation enhancement over tropical land through the lens of the moisture–precipitation relationship
Get PDFFunding: Max Planck SocietyTropical precipitation P has been found to be related to column relative humidity r by a simple relationship known as the moisture–precipitation relationship P(r). Based on one decade of daily ERA5 reanalysis data, we test whether P(r) is able to reproduce the tropical land–ocean precipitation contrast measured by , the ratio between mean precipitation over land and ocean. We find that captures the mean seasonal cycle of as long as we account for the fact that P(r) is distinct over land and ocean, and that it varies seasonally. Typical values of above 0.86 imply that precipitation is enhanced over land, relative to the ocean. We therefore investigate next whether this enhancement is due to the differences in P(r) and/or in the humidity distribution between land and ocean. We show that, rather than enhancing precipitation, the presence of land modifies P(r) in such a way that precipitation over land is disfavored compared to over ocean. Precipitation enhancement over land is instead explained by the modified terrestrial humidity distribution that features a more pronounced tail towards high r values compared to the one over ocean. All results rest on an accurate construction of P(r) from the underlying data. Simple fit models such as an exponential function that were proposed by previous studies are unable to capture the seasonal cycle of and fail to explain land–ocean differences in precipitation.Peer reviewe
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