Cystic Fibrosis Related Diabetes

Cystic fibrosis related diabetes (CFRD) is a common co-morbidity of cystic fibrosis. It is associated with diminishing lung function, poorer nutritional state, and a worse prognosis and its early diagnosis and treatment is important. In addition, the adverse pulmonary effects of CFRD may be present for up to 10 years prior to diagnosis

Si-metasomatism in serpentinized peridotite: The effects of talc-alteration on strontium and boron isotopes in abyssal serpentinites from Hole 1268a, ODP Leg 209

Ultramafic rocks recovered from Hole 1268a, Ocean Drilling Program Leg 209, to the south of the 15°20′N Fracture Zone on the Mid-Atlantic ridge have experienced a complex history of melt depletion and subsequent interaction with a series of fluids under varying temperature and pH conditions. After intense melt depletion, varying degrees of serpentinization at 100–200 °C took place, initially under seawater-like pH conditions. Subsequently, interaction with a higher temperature (300–350 °C) fluid with low (4–5) pH and low MgO/SiO2 resulted in the heterogeneous alteration of these serpentinites to talc-bearing ultramafic lithologies. The proximity of the currently active, high temperature Logatchev hydrothermal field, located on the opposite flank of the Mid-Atlantic ridge, suggests that unlike more distal localities sampled during ODP Leg 209, Hole 1268a has experienced Si-metasomatism (i.e. talc-alteration) by a Logatchev-like hydrothermal fluid. Serpentinite strontium isotope ratios were not materially shifted by interaction with the subsequent high-T fluid, despite the likelihood that this fluid had locally interacted with mid-ocean ridge gabbro. 87Sr/86Sr in the ultramafic lithologies of Hole 1268a are close to that of seawater (c.0.709) and even acid leached serpentinites retain 87Sr/86Sr in excess of 0.707, indistinguishable from Logatchev hydrothermal fluid. On the other hand, boron isotope ratios appear to have been shifted from seawater-like values in the serpentinites (δ11B = c.+40‰) to much lighter values in talc-altered serpentinites (δ11B = +9 to +20‰). This is likely a consequence of the effects of changing ambient pH and temperature during the mineralogical transition from serpentine to talc. Heterogeneous boron isotope systematics have consequences for the composition of ultramafic portions of the lithosphere returned to the convecting mantle by subduction. Inhomogeneities in δ11B, [B] and mineralogy introduce significant uncertainties in the prediction of the composition of slab fluids released during the early- to mid-stages of subduction

The Crystal Hotel: A Microfluidic Approach to Biomimetic Crystallization

A “crystal hotel” microfluidic device that allows crystal growth in confined volumes to be studied in situ is used to produce large calcite single crystals with predefined crystallographic orientation, microstructure, and shape by control of the detailed physical environment, flow, and surface chemistry. This general approach can be extended to form technologically important, nanopatterned single crystals

Advanced Multilevel Node Separator Algorithms

A node separator of a graph is a subset S of the nodes such that removing S and its incident edges divides the graph into two disconnected components of about equal size. In this work, we introduce novel algorithms to find small node separators in large graphs. With focus on solution quality, we introduce novel flow-based local search algorithms which are integrated in a multilevel framework. In addition, we transfer techniques successfully used in the graph partitioning field. This includes the usage of edge ratings tailored to our problem to guide the graph coarsening algorithm as well as highly localized local search and iterated multilevel cycles to improve solution quality even further. Experiments indicate that flow-based local search algorithms on its own in a multilevel framework are already highly competitive in terms of separator quality. Adding additional local search algorithms further improves solution quality. Our strongest configuration almost always outperforms competing systems while on average computing 10% and 62% smaller separators than Metis and Scotch, respectively

Transmission and lineage displacement drive rapid population genomic flux in cystic fibrosis airway infections of a Pseudomonas aeruginosa epidemic strain

Pseudomonas aeruginosa chronic infections of cystic fibrosis (CF) airways are a paradigm for within-host evolution with abundant evidence for rapid evolutionary adaptation and diversification. Recently emerged transmissible strains have spread globally, with the Liverpool Epidemic Strain (LES) the most common strain infecting the UK CF population. Previously we have shown that highly divergent lineages of LES can be found within a single infection, consistent with super-infection among a cross-sectional cohort of patients. However, despite its clinical importance, little is known about the impact of transmission on the genetic structure of these infections over time. To characterize this, we longitudinally sampled a meta-population of 15 genetic lineages within the LES over 13 months among seven chronically infected CF patients by genome sequencing. Comparative genome analyses of P. aeruginosa populations revealed that the presence of coexisting lineages contributed more to genetic diversity within an infection than diversification in situ. We observed rapid and substantial shifts in the relative abundance of lineages and replacement of dominant lineages, likely to represent super-infection by repeated transmissions. Lineage dynamics within patients led to rapid changes in the frequencies of mutations across suites of linked loci carried by each lineage. Many loci were associated with important infection phenotypes such as antibiotic resistance, mucoidy and quorum sensing, and were repeatedly mutated in different lineages. These findings suggest that transmission leads to rapid shifts in the genetic structure of CF infections, including in clinically important phenotypes such as antimicrobial resistance, and is likely to impede accurate diagnosis and treatment

Recent Advances in Graph Partitioning

We survey recent trends in practical algorithms for balanced graph partitioning together with applications and future research directions

Prognostic factors in oral cancer surgery - results from a UK tertiary centre

Introduction Oral cancer surgery is complicated by the diverse nature of clinical and histopathological presentations that occur. Current National guidance recognises the significant role that surgical margin status plays in the overall survival of patients. Many other histopathological factors influence patient survival, the importance of which varies between the literature. Materials and methods In this prospective longitudinal study, all patients diagnosed with squamous cell carcinoma who had primary surgical treatment under general anaesthesia were included. Surgery was performed by one surgical team within this tertiary referral centre. Patients were followed up for a maximum of 7 years following their surgery. Results A total of 250 patients were included from 2015 to 2022. Patients were 61.44 years old (SD 13.23) at diagnosis, and 56.4% were male (n = 141). Pathology was mainly pT1 (39.1%) and the most common sites were the border of tongue (31.2%) and floor of mouth (18.8%). 43.4% of patients had clear surgical margins, with overall survival being significantly associated with margin status (p = 0.0079). Extra-capsular spread was significantly associated with higher risk of death from metastatic head and neck cancer (p = 0.014), whereas presence of high-grade dysplasia at surgical margins and depth of invasion of tumour were not. Conclusion This study has reinforced the importance of surgical margin clearance and as such the development of intra-operative techniques to ensure this is imperative. The significance of extra-capsular spread in survival has also been demonstrated. Discussion regarding the current deficiency in accurate pre-operative diagnostic methods for extra capsular spread is covered