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The importance of comorbidities at baseline and 5-Year follow-up in a lung cancer biomarker screening trial
No full textBackground/Objectives: Despite recent lung cancer screening (LCS) studies proving significant mortality reduction, comorbidities are a prominent issue affecting cost effectiveness, which is holding back national implementation. Incidental findings (IFs) of comorbidities make a significant contribution to delayed diagnoses and raise discussions about optimal management plans. This is particularly relevant to national lung cancer screening (NLCS), as the high-risk population qualifying for the screening often have increased likelihood for comorbidities due to their smoking history. Methods: The Early Detection of Cancer of the Lung Scotland (ECLS) (ClinicalTrials.gov identifier NCT01925625) study showcases a targeted approach to NLCS by implementing the blood-based biomarker EarlyCDT-Lung test. Firstly, this paper explored the ECLS dataset for comorbidities present within the screening population at baseline A chi-square analysis was then undertaken to investigate the relationship of cohort allocation and incidence of new comorbidities over the five-year follow-up period. Results: High prevalence conditions were cardiovascular (38.5%), neurological/psychiatric (33.9%), gastrointestinal (29.8%), and respiratory (19.2%). While 20.3% of the total patient cohort showed a newly discovered comorbidity, there was no significant variation in new incidences between the intervention and control cohort. Conclusions: When considering these results alongside the all-cause mortality reduction shown in previous analyses, they indicate that this targeted approach to LCS might help improve the benefit–harm ratio through the introduction of biomarkers. Further refining selection criteria for low-dose CT screening might contribute to minimising the risk of overdiagnosis and overtreatment
Component graphs of vector spaces and zero-divisor graphs of ordered sets
No full textIn this paper, nonzero component graphs and nonzero component union graphs of finite-dimensional vector spaces are studied using the zero-divisor graph of a specially constructed 0–1-distributive lattice and the zero-divisor graph of rings. Furthermore, we define an equivalence relation on nonzero component graphs and nonzero component union graphs to deduce that these graphs are the graph join of zero-divisor graphs of Boolean algebras and complete graphs. The last section characterizes the perfect and chordal nonzero component and nonzero component union graphs. Additionally, we observe that the nonzero component graph and reduced nonzero component union graph of free semi-modules could be treated as the zero-divisor graph of a 0–1-distributive lattice
Isotopically heavy sulfur in nephelinite from Etinde, Cameroon Volcanic Line:implications for the origin of intraplate magmatism
No full textIntraplate magmatism has traditionally been linked to anomalously hot mantle (hotspots) transported upwards from deep-sourced mantle plumes. However, many intraplate magmatic provinces lack convincing evidence for a mantle-plume origin, and the Cameroon Volcanic Line (CVL) located on the West African continental margin is one such province. Despite being active for ca. 65 million years, it lacks the time-progressive volcanic activity that would suggest the presence of a fixed mantle hotspot or plume; instead CVL magmatism has been linked to a shallow, enriched asthenospheric source. Etinde, a relatively young (<1 Ma) volcano located at the centre of the CVL on the continent-ocean boundary, is the most silica-undersaturated and incompatible element-enriched volcano in the region and forms the focus of this study. It is constructed almost entirely of feldspar-free nephelinite lava flows, with compositions ranging from olivine nephelinite to felsic leucite nephelinite. We report new sulfide-, sulfate- and bulk-δ34S data for a suite of Etinde rock samples; the first sulfur-isotope data for the CVL. Strong (∼8 ‰) S-isotope fractionation between sulfide and sulfate (haüyne, nosean) phases suggest equilibration temperatures of ∼600 °C, well below the magma solidus temperature and likely due to sub-solidus exsolution of nanoscale sulfide particles from the sulfate phenocryst phases. The most mafic samples from Etinde have been extensively degassed, containing less than 60 ppm sulfur, and therefore cannot be used to constrain the primary δ34S. Instead, we use the intermediate and felsic volcanic rocks, where sulfur is locked in phenocrysts of haüyne and nosean, respectively. Bulk δ34S of these rocks, which best represents the primary magmatic values, ranges from +3.7 ‰ to +6.3 ‰, a heavier signature than previously reported in alkaline igneous rocks. We propose that the heavy sulfur isotope values, together with the extreme silica undersaturation and incompatible element concentrations, reflect enrichment of the mantle source and fingerprint carbonate metasomatism in the mantle beneath the CVL. The heavy sulfur isotopic signature requires low-temperature fractionation and therefore implies the addition of sulfur through subduction processes. Our study has broad geochemical significance in contributing to a growing understanding of sulfur-isotope compositional variability in geochemically enriched mantle globally
Exploring the activity of the putative Δ6-desaturase and its role in bloodstream form life-cycle transitions in <i>Trypanosoma brucei</i>
No full textTrypanosomatids have been shown to possess an exclusive and finely regulated biosynthetic pathway for de novo synthesis of fatty acids (FAs) and particularly of polyunsaturated fatty acids (PUFAs). The key enzymes for the process of unsaturation are known as desaturases. In this work, we explored the biocatalytic activity of the putative Δ6-desaturase (Tb11.v5.0580) in the native organism T. brucei, whose expression level varies dramatically between life cycle stages. Utilising FA analysis via GC-MS, we were able to elucidate i) via genetic manipulation of the level of expression of Δ6-desaturases in both procyclic (PCF) and bloodstream (BSF) forms of T. brucei and ii) via supplementation of the media with various levels of FA sources, that docosahexaenoic acid (22:6) and/or docosapentaenoic acid (22:5) are the products, while arachidonic acid (20:4) and/or docosatetraenoic acid (22:4) are the substrates of this Δ6-desaturase. Surprisingly, we were able to observe, via lipidomic analysis with ESI-MS/MS, an increase in inositol-phosphoryl ceramide (IPC) in response to the overexpression of Δ6-desaturase in low-fat media in BSF. The formation of IPC is normally only observed in the stumpy and procyclic forms of T. brucei. Therefore, the expression levels of Δ6-desaturases, which increases between BSF, stumpy and PCF, might be involved in the cascade(s) of metabolic events that contributes to these remodelling of the lipid pools and ultimately morphological changes, which are key to the transition between these life-cycle stages. We were in fact able to show that the overexpression of Δ6-desaturase is indeed linked to the expression of protein associated with differentiation (PAD1) in stumpy, and of the upregulation of some proteins and metabolites which are normally upregulated in stumpy and PCF
A primate grammar enabling incremental processing
No full textCharacterizing the structure and function of animal communication systems provides insights into the cognitive and evolutionary processes shaping signal complexity. One key question is whether and how call sequences allow potential listeners to make predictions about the call-eliciting referents. Here, we investigated whether primate call sequences contained properties that enabled such predictive processing. We analyzed several years of experimentally elicited alarm responses from a West African forest primate, wild Olive colobus monkeys. Using Kullback-Leibler Divergence and Prediction Gain approaches, we identified a simple primate grammar that allowed predictions of referents from only minimal input. In particular, sequence-initial positions reliably discriminated urgent from non-urgent threats while the following positions increased the referential specificity regarding two main predators (eagles, leopards) and non-predatory disturbances (falling tree parts). Sequences often contained further calls, which may allow callers to either confirm the referent or to alter the conveyed information. We concluded that animal communication can contain features adapted for predictive, incremental processing, suggesting evolutionary roots older than language
Evaluation of Arclight frugal smartphone video otoscopy
No full textBackground: Frugal innovations are essential in low-resource settings to provide cost-effective medical solutions without compromising functionality. The Arclight is a robust, solar-powered device that functions as both an ophthalmoscope and an otoscope, priced at approximately 12€ in low- and middle-income countries (LMICs). Objectives: This study evaluates the Arclight's potential as a video otoscope when attached to smartphones, aiming to enhance telemedicine capabilities in ear examinations. Methods: Twenty otorhinolaryngology (ORL) specialists rated the standalone Arclight as well as its attachment to an iPhone 12 and a Samsung Galaxy A14 for ear examinations at the University Medical Centre in Mainz, Germany. Results: The standalone Arclight received the highest ratings overall, followed by the Arclight attached to a Samsung Galaxy A14. Attached to the Samsung Galaxy A14, the Arclight demonstrated significantly higher performance regarding ease of focus (p < 0.01), quality of view (p < 0.05), and zoom capabilities (p < 0.05) compared to the iPhone12 attachment. The iPhone12 setup performed lowest in all categories. Conclusion: The Arclight is an effective, low-cost tool for ear examinations in low-resource settings. While smartphone integration enhances its potential for telemedicine, performance varies depending on the smartphone used. The Samsung Galaxy A14 proved to be a more reliable option for tele-otoscopy than the iPhone 12. Further optimization is needed to improve smartphone integration and address identified limitations, enhancing the Arclight's utility in telemedicine applications. Level of Evidence: NA.</p
The regional system and sectarianization in Syria
No full textThis chapter examines the interaction between the Syrian conflict and the regional struggle for power. It first examines the regional systemic structures in which the struggle for Syria took place. It analyses how the relation between geo-politics and identity shaped the distinctive dynamics of the regional system: how specifically, has sectarianism affected the practices of the regional system and how does the systemic structure – the realist rules of anarchic systems – affect sectarianism? The chapter then traces the evolution of the regional power struggle from the 2000s, identifying the structural forces working for and against sectarianization. It then looks at agency, examining the Syria policies of the major actors intervening in the Syrian conflict, how these affected the struggle for Syria and especially how far their strategies and practices were sectarianizing. It then summarizes how the regional system impacted on the struggle for Syria and how the latter was a factor in the regional power struggle
<i>The Extraordinary Journey of David Ingram: An Elizabethan sailor in Native North America</i> by D. Snow
No full textReview of Mendieta, Eduardo, <i>The Philosophical Animal: On Zoopoetics and Interspecies Cosmopolitanism</i>
No full textRecombinant production platform for Group A Streptococcus glycoconjugate vaccines
No full textGroup A Streptococcus (Strep A) is a human-exclusive bacterial pathogen killing annually more than 500,000 patients, and no current licensed vaccine exists. Strep A bacteria are highly diverse, but all produce an essential, abundant, and conserved surface carbohydrate, the Group A Carbohydrate, which contains a rhamnose polysaccharide (RhaPS) backbone. RhaPS is a validated universal vaccine candidate in a glycoconjugate prepared by chemical conjugation of the native carbohydrate to a carrier protein. We engineered the Group A Carbohydrate biosynthesis pathway to enable recombinant production using the industry standard route to couple RhaPS to selected carrier proteins within Escherichia coli cells. The structural integrity of the produced recombinant glycoconjugate vaccines was confirmed by Nuclear Magnetic Resonance (NMR) spectroscopy and mass spectrometry. Purified RhaPS glycoconjugates elicited carbohydrate-specific antibodies in mice and rabbits and bound to the surface of multiple Strep A strains of diverse M-types, confirming the recombinantly produced RhaPS glycoconjugates as valuable vaccine candidates