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Light sheet microscope scanning of biointegrated 2 microlasers for localized refractive index sensing
Get PDFFunding: M.S. acknowledges funding by the Royal Society (Dorothy Hodgkin Fellowship, DH160102; Research Grant, RGF\R1\180070; Enhancement Award, RGF\EA\180051)Whispering gallery mode (WGM) microlasers are highly sensitive to localized refractive index changes allowing to link their emission spectrum to various chemical, mechanical, or physical stimuli. Microlasers recently found applications in biological studies within single cells, in three-dimensional samples such as multicellular spheroids, or in vivo. However, detailed studies of biological samples also need to account for the structural heterogeneity of tissues and live animals, therefore requiring a combination of high-resolution microscopy and laser spectroscopy. Here, we design and construct a light sheet fluorescence microscope with a coupled spectrometer for use in microlaser studies for combined high-resolution, high-speed imaging and WGM spectral analysis. The light sheet illumination profile and the decoupled geometry of excitation and emission hereby directly affect the lasing and sensing properties, mainly through geometric constraints and by light coupling effects. We demonstrate the basic working principle of microlaser spectroscopy under light sheet excitation and measure the absolute refractive index within agarose and in zebrafish tail muscle tissue. We further analyze the light coupling conditions that lead to the occurrence of two separate oscillation planes. These so-called cross modes can be scanned around the entire microlaser surface, which allows to estimate a surface-averaged refractive index profile of the microlaser environment.Peer reviewe
An exploration of unusual antimicrobial resistance phenotypes in Salmonella Typhi from Blantyre, Malawi reveals the ongoing role of IncHI1 plasmids
Get PDFFunding: Grant information: EH acknowledges funding from Wellcome (217303/Z/19/Z) and the UKRI-BBSRC (BB/V011278/1). NAF acknowledges support by the Bill & Melinda Gates Foundation (Investment OPP1128444) and the Wellcome Programme (grant 206454).Typhoid fever is a significant public health problem endemic in Southeast Asia and Sub-Saharan Africa. Antimicrobial treatment of typhoid is however threatened by the increasing prevalence of antimicrobial resistant (AMR) S. Typhi, especially in the globally successful lineage (4.3.1) which has rapidly spread in East and Southern Africa. AMR elements can be found either on plasmids or in one of the three chromosomal integration sites, and there is variability of this across the lineage. Several previous studies with Malawian isolates indicated a clonal, locally spreading lineage with chromosomally integrated resistance genes. In a recent study however we noted three isolates with predicted resistance genes unusual for the region, and we here present the resolved genomes of these isolates using long- and short-read sequencing. Our work shows that these isolates are potentially imported cases, most closely related to the recently described sub-lineage 4.3.1.EA1, although they encode IncHI1 plasmids with reduced resistance gene repertoire compared to the main IncHI1 plasmids spreading in East Africa. Similar reduced plasmids were reported in a recent large-scale study in five isolates from Tanzania, highlighting the urgency for better coverage of the African continent in genome studies to better understand the dynamics of these potentially co-circulating plasmids.Peer reviewe
Use of Augmentative Interspecies Communication devices in animal language studies : a review
Get PDFCountless discussions have been generated by the animal language studies, specifically those utilizing mechanical interfaces, termed here Augmentative Interspecies Communication (AIC) devices (e.g., lexigrams; magnetic chips; keyboards). Overall, three concerns dominate the field: (1) claims that AIC device using animals manifest linguistic skills remain nebulous, and simpler alternative mechanisms have been proposed (e.g., associative learning); (2) such methodology may be unsuitable as some theorize AIC device interfaces are not sufficiently ecologically relevant to foster meaningful use; (3) data may be considered dubious due to potential cueing from experimenters and lack of systematicity in reporting training and performance. Despite such controversy-which eventually led to the field's deterioration around the last quarter of the twentieth century-this research also saw important successes, such as improvements in captive animal welfare, the outcomes of which hold promise for future interspecies communication work. This article is categorized under: Linguistics > Evolution of Language.Peer reviewe
Enhancing diagnostic accuracy of ophthalmological conditions with complex prompts in GPT-4 : comparative analysis of global and low- and middle-income country (LMIC)–specific pathologies
Get PDFBackground: The global incidence of blindness has continued to increase, despite the enactment of a Global Eye Health Action Plan by the World Health Assembly. This can be attributed, in part, to an aging population, but also to the limited diagnostic resources within low- and middle-income countries (LMICs). The advent of generative artificial intelligence (AI) within health care could pose a novel solution to combating the prevalence of blindness globally. Objective: The objectives of this study are to quantify the effect the addition of a complex prompt has on the diagnostic accuracy of a commercially available LLM, and to assess whether such LLMs are better or worse at diagnosing conditions that are more prevalent in LMICs. Methods: Ten clinical vignettes representing globally and LMIC-prevalent ophthalmological conditions were presented to GPT-4‐0125-preview using simple and complex prompts. Diagnostic performance metrics, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), were calculated. Statistical comparison between prompts was conducted using a chi-square test of independence. Results: The complex prompt achieved a higher diagnostic accuracy (90.1%) compared to the simple prompt (60.4%), with a statistically significant difference (χ2=428.86; P<.001). Sensitivity, specificity, PPV, and NPV were consistently improved for most conditions with the complex prompt. The simple prompt struggled with LMIC-prevalent conditions, diagnosing only 1 of 5 accurately, while the complex prompt successfully diagnosed 4 of 5. Conclusions: The study established that overall, the inclusion of a complex prompt positively affected the diagnostic accuracy of GPT-4‐0125-preview, particularly for LMIC-prevalent conditions. This highlights the potential for LLMs, when appropriately tailored, to support clinicians in diverse health care settings. Future research should explore the generalizability of these findings across other models and specialties.Peer reviewe
Coulomb blockade thermometry based nanocalorimetry
Get PDFFunding: The authors acknowledge funding from the Engineering and Physical Sciences Research Council (Grant Nos. EP/P024564/1, EP/V049410/1, and EP/L015110/1) as well as the IMPRS-CPQM.Specific heat is a powerful probe offering insights into the entropy and excitation spectrum of the studied material. While it is well established, a key challenge remains the measurement of microcrystals or thin films, especially in the sub-Kelvin, high magnetic field regime. Here, we present a setup combining the high sensitivity of SiNx membrane based calorimetry with the absolute accuracy of Coulomb blockade thermometry to realize a nanocalorimeter for such tasks. The magnetic field independent technique of Coulomb blockade thermometry provides an on-platform thermometer combining a primary thermometry mode for in situ calibration with a fast secondary mode suitable for specific heat measurements. The setup is validated using measurements of a 20 μg sample of Sr3Ru2O7, achieving a resolution on the order of 0.1 nJ K−1 at 500 mK and an absolute accuracy limited by the determination of the sample’s mass. Measurements of CeRh2As2 further highlight the benefits of measuring microcrystals with such a device.Peer reviewe
Clinical chemistry reference intervals for health assessment in wild adult harbour seals
Get PDFFunding: This research was funded by the UK Natural Environment Research Council National Capability—National Public Good funding (NE/R015007/1 and NE/Y006194/1), the Department for Energy Security and Net Zero (DESNZ; OESEA-22-145), Defra (C20796–ME6062), Scottish Government ScotMER and Marine Mammal Scientific Support Research Programmes. Funding for the samples collected in the Moray Firth was provided by Moray Offshore Wind Farm (West) Ltd., Moray Offshore Wind Farm (East) Ltd., Beatrice Offshore Wind Ltd., Marine Scotland, and Nature Scot.Reference intervals for clinical chemistry blood parameters are valuable for both individual diagnostics for animals in managed or veterinary care, and for evaluating wild population health. However, for marine mammals obtaining sufficient data from suitable groups or populations is logistically difficult. Here, we have assembled a large dataset of clinical chemistry results from free-living adult UK harbour seals (Phoca vitulina), analysed in the same commercial laboratory. We applied an open-source algorithm (available as the R package refineR, R version 4.5.2, refineR version 2.0.0) to produce robust reference intervals from these Real-World Data. This novel approach resulted in the generation of 95% reference intervals with 90% confidence bounds for 18 key chemistry parameters indicative of a range of physiological processes including, inflammation, nutritional status, kidney function and liver function. Reference intervals were also generated for triiodothyronine, the active thyroid hormone important in the regulation of metabolism. These intervals will provide critical baseline data for the assessment of harbour seal health as, to our knowledge, this is the largest dataset on which clinical chemistry reference intervals from wild-caught adult harbour seals have been based.Peer reviewe
The comparison between Arclight loupe and handheld Slit lamp in anterior segment eye disease diagnosis
Get PDFFunding: The study was funded by the Makerere Research & Innovations Fund 3 (MAKRIF/CH/02/21). Matched funding was also secured from the University of St. Andrews in Scotland for purchasing Arclight medical devices. AWS was a research fellow of the MakNCD program(D43TW011401) supported by the Fogarty International Centre of the National Institutes of Health. JM was a Ph.D. student awarded under the Nurturing Genomics and Bioinformatics Research Capacity in Africa (BRECA) grant (U2RTW010672) from the Fogarty International Centre of the National Institutes of Health.Introduction: Early diagnosis of eye diseases improves outcomes and reduces blindness. However, diagnostic capacity in resource-poor settings is limited by a shortage of trained and equipped healthcare professionals. The Arclight device is a user-friendly, cost-effective diagnostic tool for both anterior and posterior segment eye diseases that requires minimal training. Studies have shown it to be effective for assessing the fundal reflex and performing fundoscopy; however, its accuracy and acceptability for anterior segment eye disease are still unknown. Methods: This was a cross-sectional study carried out at Mulago National Super Specialised Hospital, where 21 ophthalmic clinical officers (OCOs) were recruited from surrounding districts. Each participant evaluated eleven patients with anterior segment pathologies and one normal case using the Arclight loupe and a handheld Slit Lamp. The diagnosis and the proportion of correctly identified conditions were recorded. Focus group discussions were held to assess the acceptability of using the devices. Discussions were transcribed verbatim and analysed using latent and manifest content analysis. Results: Of the 21 participants, 13 (61.9%) were female, with a median age of 39 (IQR: 33– 49), and had practiced for 6 to 10 years, representing 76.2%. The majority of conditions were correctly identified by both the Arclight (71.2%) and handheld slit lamp (72.3%). Pterygium was the most accurately diagnosed condition (100%) with the Arclight. Based on themes from Sekhon’s framework and the Technology Acceptance Model, the Arclight device was found to be highly acceptable and easy for OCOs to use. Conclusion: The performance of the OCOs in diagnosing anterior segment diseases with the Arclight is comparable to that of a handheld Slit lamp. It was also found to be an acceptable device for diagnostic purposes. In conclusion, the Arclight device is a suitable, low-cost alternative to the handheld Slit Lamp, especially in resource-limited settings.Peer reviewe
Longitudinal and bidirectional relationships between sleep, emotional wellbeing and weight status in childhood and adolescence : growing up in Scotland cohort analysis
Get PDFFunding: This work was supported by the University of St Andrews and University of Edinburgh.Poor sleep and emotional wellbeing, which often decline during puberty, are associated with declines in metabolic health and are key determinants of childhood obesity. The aim of the study was to explore bidirectional associations between sleep, emotional wellbeing and obesity from ages 8 to 14 using the Growing Up in Scotland cohort. Secondary analyses were conducted on data from sweeps 7–10 (ages 8–14). Sleep duration was caregiver-reported at age 8 and self-reported at 14. Obesity was assessed using BMI percentiles (BMIp), derived from objective height and weight at ages 8, 10, 12 and 14. Emotional wellbeing was assessed using the Strengths and Difficulties Questionnaire caregiver-report at 10 and 12 years, and self-report at 14 years. Pearson correlations and adjusted regressions examined associations between sleep, BMIp and emotional wellbeing from ages 8 to 14. Analyses included 4157 participants (50.2% male). Shorter sleep at 8 years was associated with higher BMIp at 12 years (β = −0.172, CI (95%) = −0.335, −0.116, p < 0.001) and poorer emotional wellbeing at 10 (β = −0.120, CI (95%) = −0.179, −0.034, p < 0.001) and 12 years (β = −0.101, CI (95%) = −0.164, −0.026, p < 0.001). Poorer emotional wellbeing at 10 (β = −0.116, CI (95%) = −0.232, −0.093, p < 0.001) and 12 years (β = −0.194, CI (95%) = −0.328, −0.174, p < 0.001) predicted shorter sleep at 14 years. Higher BMIp at 8 years was associated with shorter sleep at 14 years (β = −0.182, CI (95%) = −0.359, −0.111, p < 0.001). Poorer emotional wellbeing at 10 years was associated with higher BMIp at 14 years (β = 0.142, CI (95%) = 0.074, 0.629, p = 0.13). Bidirectional associations emerged between short sleep and emotional wellbeing and higher BMIp. Poor emotional wellbeing was associated with subsequent obesity; but not bidirectionally. These interactions should inform the design of health interventions for 8–14-year-oldsPeer reviewe
High precision thermodynamic measurements and their application to quantum materials
No full textDiscoveries in condensed matter physics are often driven by the development of new capabilities or pushing the sensitivity of existing ones. This thesis covers the development and application of two such capabilities, which have revealed new details in the phase diagram of CeRh₂As₂ as well as the behaviour of Sr₃Ru₂O₇ under both external and internal (chemical) stress.
We recently developed a nanocalorimeter using primary Coulomb blockade thermometry which improves accuracy for measurements of microcrystals in magnetic fields and at low temperatures. I extended the system to lower temperatures, performing a detailed study of a high-quality microcrystal of CeRh₂As₂. My measurements for the first time properly resolve the mixed SC2 + I phase and its associated heat capacity jump. A flattening of both T_c(H) and the jump in specific heat associated with the phase are observed, with implications as to the magnetic response of the mixed SC2 + I phase. Measurements below T_c(H) also reveal weak signatures of both SC1 + I → SC2 + I and I phase transitions, the first time these have been observed in specific heat as a function of magnetic field.
I also present the development of a high-resolution dilatometer. This has a resolution better than 1 pm / √H z and allows measurements to be performed with a truly stress-free sample mounting. I present measurements of quantum oscillations in strain for both Sr₂RuO₄ and Sr₃Ru₂O₇ which allow calculation of the stress sensitivities of the Fermi surfaces in these materials. These results confirm DFT calculations and provide insight into the evolution the ruthenates under uniaxial stress. For Sr₃Ru₂O₇ I also explore the band structure evolution caused by more complex doping induced distortions, and use these to tune the Van Hove singularity through the Fermi energy.
Finally I present initial work developing both new probes for use in the PPMS, increasing their accessibility and operational temperature range."This work was supported by the International Max Planck Research School for Chemistry and Physics of Quantum Materials, the University of St Andrews School of Physics and Astronomy and the Engineering and Physical Sciences Research Council (Grant numbers EP/P024564/1 and EP/V049410/1)."--Fundin
Are beautiful theories better theories?
Get PDFDevon Brickhouse-Bryson: Judgements of beauty in theory evaluation. Maryland: Lexington Books, The Rowman & Littlefield Publishing Group, 148 pp, $90 HBNon peer reviewe
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