Pregnancy risk stratification using DESI-MS profiling of vaginal mucosa

Preterm birth is the leading cause of childhood mortality. Despite decades of research, the pathophysiology of spontaneous preterm birth (SPTB) remains poorly understood. Prevention strategies are limited by our inability to reliably predict women at risk and stratify depending on underlying aetiology. There is an established association between ascending vaginal infection and SPTB. More recently, highly diverse vaginal bacterial communities deplete of Lactobacillus species have been associated with SPTB. However, not all pregnant women with such community structures deliver preterm, highlighting the importance of individual host response. Medical swabs are routinely used for microbiological screening with culture-based techniques. However, these are time-consuming, have a narrow focus for specific microbes and provide no information regarding host response. We hypothesised that metabolic profiling of cervico-vaginal mucosa (CVM) may offer the ability to assess interactions between the vaginal microbiota and the pregnant host that are useful for prediction and stratification of SPTB risk. To address this hypothesis, we developed a technique using DESI-MS that enabled rapid acquisition of metabolic information directly from vaginal swabs. In Chapter 3, method optimisation is described and its capacity to detect variations in the CVM associated with physiological changes in the host (e.g. pregnancy) and disruptions in bacterial community compositions during pregnancy (e.g. bacterial vaginosis) are presented. The DESI-MS swab profiling approach was then used to characterise and compare CVM metabolic profiles associated with SPTB risk (Chapter 4). These results showed that the CVM metabolome associated with subsequent SPTB was highly variable, reflecting the heterogeneity of SPTB aetiology. In support of this, DESI-MS more effectively discriminated samples with differing severity of SPTB (early vs late) and phenotypes (SPTL and PPROM). In Chapter 5, DESI-MS profiling of CVM was shown to facilitate prediction of PPROM as well as enable its robust diagnosis. DESI-MS also had capacity to characterise microbial compositions following PPROM suggesting its potential to assist in directed treatment strategies based on underlying aetiology. This thesis highlights the predictive and therapeutic potential of DESI-MS in pregnancy.Open Acces

A filosofia e as raízes marxianas do pensamento político queer

Translation of an excerpt from the book The Politics of Everybody. Feminism, Queer Theory and Marxism at the Intersection (1.III, pp.46-64), published in English by Zed Books, London (2016). Lewis is a philosopher and an Associate Professor at Texas State University. This excerpt from her contribution, translated before into Spanish, appears now for the first time in Portuguese, and articulates a strongly complex debate (and, only apparently, incompatible) between Marxism, Feminism and Queer Theory.Traducción de retazo del libro La política de todes. Feminismo, teoría queer y marxismo en la intersección (1.III, pp.46-64), publicado en inglés por la editorial Zed Books, Londres (2016). Lewis es filósofa y está vinculada como profesora titular a la Universidad de Texas. Este fragmento de dicha aportación suya, ya traducida al español, aparece por primera vez en portugués y articula una discusión genuinamente delicada (y, solo aparentemente, inconciliable) entre marxismo, feminismo y teoría queer.Tradução de trecho do livro A política de todes. Feminismo, teoria queer e marxismo em intersecção (1.III, pp. 46-64), publicado em inglês (The Politics of Everybody. Feminism, Queer Theory and Marxism at the Intersection) pela Zed Books, Londres (2016). Lewis é filósofa e está vinculada como professora titular à Universidade do Texas. Este fragmento dessa contribuição sua, já traduzida ao espanhol, aparece pela primeira vez em português e articula um debate verdadeiramente espinhoso (e, só aparentemente, inconciliável) entre marxismo, feminismo e teoria queer

A Task Process Pre-Experimental Model

The Adaptive Architectures for Command and Control (A2C2) program is a multidisciplinary program that employs a scientific basis for designing and analyzing adaptive and reconfigurable organizational structures at the Joint Task Force level. As part of its unique model-driven experimentation method, a pre-experimental model is created to support the formulation of hypotheses, the determination of key variables and parameter values, and the prediction of organizational performance. The pre-experimental model is used to explore the parameters of the experimental design in order to determine the appropriate region to conduct officer-in-the-loop experiments at the Naval Postgraduate School. A pre-experimental model based on the task process was created for an upcoming A2C2 subject experiment, which will examine the congruence between organizational structure and mission requirements. The pre-experimental model is a dynamic model created with Colored Petri nets, which can represent the changes in the task environment over time by implementing the stages of the tasks (i.e., detection, identification, attack, destroy, and disappear). The simulator used in the subject experiments, Distributed Dynamic Decision-Making (DDD), records timing information over the life of each task. Therefore, timing information regarding the tasks can be extracted from the output files of the trial experimental runs and included in the model before the final experimental simulations. In this way the model can be validated at the pre-experimental stage

Assessing a novel contact heater as a new method of recovering explosives traces from porous surfaces

It can be very challenging to recover explosives traces from porous surfaces, such as clothing and car seats, compared to non-porous surfaces. The contact heater has been developed as a novel instrument designed to recover explosives traces from porous surfaces. Samples are taken by heating and drawing air across a surface, with the air flowing through a sampling cartridge containing adsorbent polymer beads, which act to trap any recovered explosive material. Any collected explosive can then be eluted from this cartridge using a solvent, prior to analysis. This paper outlines work performed to evaluate the usefulness of the contact heater with regards to the recovery of explosives traces from porous materials. Ethylene glycol dinitrate (EGDN) and triacetone triperoxide (TATP) were chosen as two representative explosives for this study. Quantification was performed using GC–MS for EGDN and LC–MS/MS for TATP. Different sampling temperatures, sampling times and elution solvents were investigated. Recovery was trialled from leather, carpet and denim. Recoveries of up to 71% were obtained following optimisation. It was also possible to recover TATP from fabrics exposed to TATP vapour in a vapour-laden jar up to two hours after exposure. The contact heater therefore appears to be a very useful tool for the recovery of explosives traces from porous materials

Efficacy of hemostatic matrix and microporous polysaccharide hemospheres

AbstractBackgroundMicroporous Polysaccharide Hemospheres (MPH) are a new plant-derived polysaccharide powder hemostat. Previous studies investigated MPH as a replacement to nonflowable hemostatic agents of different application techniques (e.g., oxidized cellulose, collagen); therefore, the purpose of this study was to determine if MPH is a surrogate for flowable hemostatic agents of similar handling and application techniques, specifically a flowable thrombin-gelatin hemostatic matrix.MethodsHemostatic efficacy was compared using a heparinized porcine abrasion model mimicking a capsular tear of a parenchymal organ. MPH (ARISTA, 1 g) and hemostatic matrix (Floseal, 1 mL) were applied, according to a randomized scheme, to paired hepatic abrasions (40 lesions per group). Hemostatic success, control of bleeding, and blood loss were assessed 2, 5, and 10 min after treatment. Hemostatic success and control of bleeding were analyzed using odds ratios and blood loss using mean differences.ResultsHemostatic matrix provided superior hemostatic success relative to MPH at 5 (odds ratio: 0.035, 95% confidence interval: 0.004–0.278) and 10 min (0.032, 0.007–0.150), provided superior control of bleeding at 5 (0.006, <0.001–0.037) and 10 min (0.009, 0.001–0.051), and had significantly less blood loss at 5 (mean difference: 0.3118 mL/min, 95% confidence interval: 0.0939–0.5296) and 10 min (0.5025, 0.2489–0.7561).ConclusionsThese findings corroborate other MPH investigations regarding its low-level efficacy and suggest that MPH is not an appropriate surrogate for hemostatic matrix despite similar application techniques. The lack of a procoagulant within MPH may likely be the reason for its lower efficacy and need for multiple applications

The stability of TNT, RDX and PETN in simulated post-explosion soils:Implications of sample preparation for analysis

Explosives residues in soils may be a useful source of evidence following the detonation of an improvised explosive device (IED), such as a vehicle-borne IED. Soil samples collected from the vicinity of an explosion scene will often be stored for some time prior to analysis, yet explosives residues in soil samples are susceptible to rapid degradation or transformation. Although some research has assessed the use of different storage temperatures with a view to reducing explosives' degradation over time, further research examining the degradation of explosives in soil when stored under a variety of storage conditions is crucial to determine the optimal sample collection and storage procedures for soil containing explosives residues. In this work, three different soils were spiked with solutions of TNT, RDX and PETN and stored either at room temperature, refrigerated or frozen. Samples were extracted over 6 weeks, with additional samples gamma-irradiated or nitrogen purged prior to storage. Experimental results indicate that TNT underwent very rapid degradation at room temperature, attributed to microbial action, whereas PETN and RDX proved to be more stable. Gamma irradiation and nitrogen purging proved of some benefit for mitigating TNT degradation, with lower storage temperatures ultimately proving the most effective method of mitigating degradation

Unethical consumption and obligations to signal

There are many different ways to try to bring about an end to the harms involved in the production of consumer goods. In this article I will start at the bottom, with the individual whose ordinary choices about how to travel, what to eat, what to wear, where to shop, and which policies to support all cause her to confront the possibility of involvement in these harms to the environment, nonhuman animals, and persons. Having dismissed the claim that an individual has a straightforward duty of justice not to consume unethically produced goods, in the second section I map out a few different approaches, all of which I take to be promising avenues for generating duties in individuals to consume ethically. I argue that the last approach is the most promising and spend the third section of this article developing it. Specifically, I argue that as a first step in collectivizing to act against unjust global labor practices, an individual ought to signal to others her commitments to ethical consumption. In section four I ask whether some signals are too cheap to function as a step toward collectivization, and defend the deliberate consumption of only ethically produced goods as a moderately costly and therefore reliable signal. In the last section I consider a challenge to the proposal in terms of whether it imposes unacceptable costs on consumers

Nitrogen-bridged, natural product-like octahydrobenzofurans and octahydroindoles: scope and mechanism of bridge-forming reductive amination via caged heteroadamantanes

The biological significance of sp3-rich synthetic scaffolds with natural product-like features yet distinct global frameworks is being increasingly recognised in medicinal chemistry and biochemistry. Taking inspiration from the vast array of bioactive, bridged alkaloids, we report the synthesis of unique, densely functionalised tricyclic scaffolds based on nitrogen-bridged, octahydrobenzofurans and octahydroindoles. These heterocycle-rich frameworks were assembled by a one-pot, two-step bridge-forming reductive amination process, which was shown to proceed via caged, heteroadamantane intermediates that thermodynamically drive an exo–endo epimerisation, enabling intramolecular azaMichael addition over the concave face of the fused bicyclic precursors. In addition to evaluating the scope of this aza bridge-forming reaction, further stereochemical complexity was introduced by subsequent diastereoselective ketone reductions and other manipulations. Finally, strategic diversity points (amino, carboxy) were decorated with common medicinal chemistry fragments, providing a set of exemplar derivatives with Lipinski compliant physicochemical properties