Development of novel mass spectrometric methods for point-of-care mucosal diagnostics

Human mucosal surfaces act as key interfaces between microbiota and host. As such, mucosal sampling using medical swabs is performed for diagnostic purposes that most commonly rely upon subsequent microscopy, culture or molecular-based assays. These approaches are limited in providing information on host response, which is a critical facet of pathology. In this thesis, I sought to test the hypothesis that both presence of specific microbes as well as their interactions with the human host are reflected in the mucosal metabolome and that this information could be exploited for mucosal diagnostic applications. The study aimed to develop a method for rapid, direct metabolic profiling from swabs using desorption electrospray ionisation mass spectrometry (DESI-MS). Method optimisation was conducted to elucidate optimal instrumental and geometrical conditions essential for the swab analysis. The application of the method for mucosal diagnostics was then assessed by characterising the metabolic profile of multiple bodysites (oral, nasal and vaginal mucosa), vaginal mucosa during two different physiological states (non-pregnant vs pregnant) and to detect a pathological state (bacterial vaginosis). Correlation of DESI-MS vaginal metabolic profiles with matched vaginal microbiota composition (VMC) characterised by 16S rRNA-based metataxonomics during pregnancy enabled to robustly predict a Lactobacillus dominant from depleted state but also major vaginal community states types (CST). The predictive performance of DESI-MS based models was comparable to “gold standard” LC-MS based models. Additionally, bacterial metabolite markers predictive of specific microbial genera were identified through matching to a spectral database constructed using pure cultures of commensal and pathogenic microbes often observed in the vaginal microbiome. In summary, DESI-MS has the potential to revolutionise the current way of mucosal based diagnostic by reducing significantly the time-demand needed for the characterisation of VMC, drug or inflammatory response to only few minutes and therefore could enable a faster decision making on patient’s treatment.Open Acces

The Relationship of Gametes to Those Who Procreate and Its Impact on Artificially Generated Gamete Technologies

Current developments in reproductive technology forecast that in the foreseeable future artificially generated gametes might be presented as a possible fertility treatment for infertile couples and for homosexual couples desiring to have children genetically originating from both partners. It is important to evaluate the ethical issues connected to this technology before its emergence. This article first reviews the meaning that gametes (sperm and eggs) might have to those who procreate, as well as their ontology. From this, suggestions are made as to what qualities artificially generated gametes need to be truly called gametes. Finally, different proposed routes for artificial gamete generation are examined on the basis of these qualities, with their prospective problems and advantages highlighted. Autotransplanted gametes (or their progenitors) generated solely from patient-derived tissue are deemed to be the most ethically suitable route for the development of this technology

What does it mean for a clinical AI to be just: conflicts between local fairness and being fit-for-purpose?

There have been repeated calls to ensure that clinical artificial intelligence (AI) is not discriminatory, that is, it provides its intended benefit to all members of society irrespective of the status of any protected characteristics of individuals in whose healthcare the AI might participate. There have also been repeated calls to ensure that any clinical AI is tailored to the local population in which it is being used to ensure that it is fit-for-purpose. Yet, there might be a clash between these two calls since tailoring an AI to a local population might reduce its effectiveness when the AI is used in the care of individuals who have characteristics which are not represented in the local population. Here, I explore the bioethical concept of local fairness as applied to clinical AI. I first introduce the discussion concerning fairness and inequalities in healthcare and how this problem has continued in attempts to develop AI-enhanced healthcare. I then discuss various technical aspects which might affect the implementation of local fairness. Next, I introduce some rule of law considerations into the discussion to contextualise the issue better by drawing key parallels. I then discuss some potential technical solutions which have been proposed to address the issue of local fairness. Finally, I outline which solutions I consider most likely to contribute to a fit-for-purpose and fair AI

Hydromedusa Seasonality and Diversity in Galveston Bay

Hydrozoa (phylum Cnidaria) is one of the most diverse and widespread classes of gelatinous zooplankton. They are understudied because they are often inconspicuous and overlooked in many planktonic studies. Due to their complex life cycle, they undergo blooms and seasonal fluctuations. However, the factors that cause their fluctuations and blooms are unknown. Hydromedusae are top predators and are in direct competition with fish for resources. They can thus significantly impact the marine ecosystem during their seasonal blooms. Therefore, it is important to understand their seasonality, both in diversity and abundance, to better understand marine food webs and manage fishing grounds such as Galveston Bay and the Gulf of Mexico. To enhance our taxonomic knowledge of Hydrozoa in Galveston Bay and understand their seasonality, plankton samples were collected locally four times a week over thirteen months. These samples were examined for both abundance and species diversity to understand how the Hydrozoa population fluctuates in response to seasonal abiotic factors such as temperature, salinity, dissolved oxygen, and chlorophyll a. Twenty-five different species were found in Galveston Bay with strong seasonality in overall abundance and species richness. Dominant species included Blackfordia virginica, Liriope tetraphylla, Clytia gracilis, Malagazzia carolinae, Nemopsis bachei and the genus Obelia. Temperature alone had strong correlation with overall medusa abundance and the majority of the dominant species. This study provides a first assessment of the composition of hydromedusa in Galveston Bay and their seasonal response to environmental factors

Spatial Distribution of Silica-Bound Catalytic Organic Functional Groups Can Now Be Revealed by Conventional and DNP-Enhanced Solid-State NMR Methods

Understanding the spatial distribution of functionalities on surfaces with atomic-scale resolution is very important for catalytic applications, yet very challenging for analytical inquiry. Recent advances in solid-state nuclear magnetic resonance (SSNMR), especially in dynamic nuclear polarization and fast magic-angle spinning, offer new tools for examining this longstanding problem. The aim of this Perspective is to showcase how these SSNMR methods can shed light on the uniformity of surface functionalities deployed on mesoporous silica-based catalysts using post-synthesis grafting and co-condensation methods. The results are discussed in the context of earlier landmark studies on the spatial distributions of surface species using probe molecules and reactions

Why are there no platypuses at the Olympics?: A teleological case for athletes with disorders of sexual development to compete within their sex category

In mid-2019, the controversy regarding South African runner Caster Semenya’s eligibility to participate in competitions against other female runners culminated in a Court of Arbitration for Sport judgement. Semenya possessed high endogenous testosterone levels (arguably a performance advantage), secondary to a disorder of sexual development. In this commentary, Aristotelean teleology is used to defend the existence of ‘male’ and ‘female’ as discrete categories. It is argued that once the athlete’s sex is established, they should be allowed to compete in the category of their sex without obligatory medical treatment. Indeed, other athletes who possess advantageous genetic or phenotypic traits that fall outside of the human norm have been allowed to compete as humans without restraint. In both cases, if an athlete possesses the essential attributes of being a human or being male or female they should be permitted to compete in those respective categories; athletes’ eligibilities should not be based upon accidental attributes