Comparison of Microbiomes from Different Niches of Upper and Lower Airways in Children and Adolescents with Cystic Fibrosis

Changes in the airway microbiome may be important in the pathophysiology of chronic lung disease in patients with cystic fibrosis. However, little is known about the microbiome in early cystic fibrosis lung disease and the relationship between the microbiomes from different niches in the upper and lower airways. Therefore, in this cross-sectional study, we examined the relationship between the microbiome in the upper (nose and throat) and lower (sputum) airways from children with cystic fibrosis using next generation sequencing. Our results demonstrate a significant difference in both α and β-diversity between the nose and the two other sampling sites. The nasal microbiome was characterized by a polymicrobial community while the throat and sputum communities were less diverse and dominated by a few operational taxonomic units. Moreover, sputum and throat microbiomes were closely related especially in patients with clinically stable lung disease. There was a high inter-individual variability in sputum samples primarily due to a decrease in evenness linked to increased abundance of potential respiratory pathogens such as Pseudomonas aeruginosa. Patients with chronic Pseudomonas aeruginosa infection exhibited a less diverse sputum microbiome. A high concordance was found between pediatric and adult sputum microbiomes except that Burkholderia was only observed in the adult cohort. These results indicate that an adult-like lower airways microbiome is established early in life and that throat swabs may be a good surrogate in clinically stable children with cystic fibrosis without chronic Pseudomonas aeruginosa infection in whom sputum sampling is often not feasible.

Prosthodontic rehabilitation of a patient using a swing-lock lower denture after segmental mandibulectomy

A swing-lock denture is useful in partially dentate patients where the configuration of the remaining teeth means that either the retention or stability available for a conventional removable partial denture is compromised. Such removable prostheses can also prove to be extremely useful when providing prosthodontic rehabilitation following surgical resection of oral cancer. A 20 year-old patient was referred to the Restorative Department of Cork University Dental Hospital following segmental mandibulectomy to treat a calicifying epithelial odontogenic tumour (Pindborg Tumour). Initial treatment using a conventional lower partial denture failed. This paper outlines the successfully rehabilitation using a lower Cobalt-Chromium swing-lock partial denture.

Diagenetic Alterations and Reservoir Quality Evolution of Lower Cretaceous Fluvial Sandstones: Nubian Formation, Sirt Basin, North-Central Libya

Lower Cretaceous meandering and braided fluvial sandstones of the Nubian Formation form some of the most important subsurface reservoir rocks in the Sirt Basin, north-central Libya. Mineralogical, petrographical and geochemical analyses of sandstone samples from well BB6-59, Sarir oilfield, indicate that the meandering fluvial sandstones are fine- to very fine-grained subarkosic arenites (av. Q91F5L4), and that braided fluvial sandstones are medium- to very coarse-grained quartz arenites (av. Q96F3L1). The reservoir qualities of these sandstones were modified during both eodiagenesis (ca. <70oC; <2 km) and mesodiagenesis (ca. >70oC; >2km). Reservoir quality evolution was controlled primarily by the dissolution and kaolinitization of feldspars, micas and mud intraclasts during eodiagenesis, and by the amount and thicknessof grain-coating clays, chemical compaction and quartz overgrowths during mesodiagenesis. However, dissolution and kaolinitization of feldspars, micas and mud intraclasts resulted in the creation of intercrystalline micro- and mouldic macro-porosity and permeability during eodiagenesis, which were more widespread in braided fluvial than in meandering fluvial sandstones. This was because of the greater depositional porosity and permeability in the braided fluvial sandstones which enhanced percolation of meteoric waters. The development of only limited quartz overgrowths in the braided fluvial sandstones, in which quartz grains are coated by thick illite layers, retained high porosity and permeability (12-23 % and 30- 600 mD). By contrast, meandering fluvial sandstones underwent porosity loss as a result of quartz overgrowth development on quartz grains which lack or have thin and incomplete grain-coating illite (2-15 % and 0-0.1mD). Further loss of porosity in the meandering fluvial sandstones occurred as a result of chemical compaction (pressuredissolution) induced by the occurrence of micas along grains contacts. Otherdiagenetic alterations, such as the growth of pyrite, siderite, dolomite/ankerite and albitization, had little impact on reservoir quality. The albitization of feldspars may have had minor positive influence on reservoir quality throughthe creation of intercrystalline micro-porosity between albite crystals.The results of this study show that diagenetic modifications of the braided and meandering fluvial sandstones in the Nubian Formation, and resulting changes in reservoir quality, are closely linked to depositional porosity and permeability. They are also linked to the thickness of grain-coating infiltrated clays, and to variations in detrital composition, particularly the amounts of mud intraclasts, feldspars and mica grains as well as climatic conditions.

Computing lower and upper expectations under epistemic independence

This paper investigates the computation of lower/upper expectations that must cohere with a collection of probabilistic assessments and a collection of judgements of epistemic independence. New algorithms, based on multilinear programming, are presented, both for independence among events and among random variables. Separation properties of graphical models are also investigated.

Relative Contribution of P5 and Hap Surface Proteins to Nontypable Haemophilus influenzae Interplay with the Host Upper and Lower Airways

Nontypable Haemophilus influenzae (NTHi) is a major cause of opportunistic respiratory tract disease, and initiates infection by colonizing the nasopharynx. Bacterial surface proteins play determining roles in the NTHi-airways interplay, but their specific and relative contribution to colonization and infection of the respiratory tract has not been addressed comprehensively. In this study, we focused on the ompP5 and hap genes, present in all H. influenzae genome sequenced isolates, and encoding the P5 and Hap surface proteins, respectively. We employed isogenic single and double mutants of the ompP5 and hap genes generated in the pathogenic strain NTHi375 to evaluate P5 and Hap contribution to biofilm growth under continuous flow, to NTHi adhesion, and invasion/phagocytosis on nasal, pharyngeal, bronchial, alveolar cultured epithelial cells and alveolar macrophages, and to NTHi murine pulmonary infection. We show that P5 is not required for bacterial biofilm growth, but it is involved in NTHi interplay with respiratory cells and in mouse lung infection. Mechanistically, P5NTHi375 is not a ligand for CEACAM1 or α5 integrin receptors. Hap involvement in NTHi375-host interaction was shown to be limited, despite promoting bacterial cell adhesion when expressed in H. influenzae RdKW20. We also show that Hap does not contribute to bacterial biofilm growth, and that its absence partially restores the deficiency in lung infection observed for the ΔompP5 mutant. Altogether, this work frames the relative importance of the P5 and Hap surface proteins in NTHi virulence.

Higher effort-reward imbalance and lower job control predict exit from the labour market at the age of 61 years or younger: Evidence from the English Longitudinal Study of Ageing

Background: We examined whether higher effort-reward imbalance (ERI) and lower job control are associated with exit from the labour market. 

Methods: There were 1263 participants aged 50-74 years from the English Longitudinal Study on Ageing with data on working status and work-related psychosocial factors at baseline (wave 2; 2004-2005), and working status at follow-up (wave 5; 2010-2011). Psychosocial factors at work were assessed using a short validated version of ERI and job control. An allostatic load index was formed using 13 biological parameters. Depressive symptoms were measured using the Center for Epidemiologic Studies Depression Scale. Exit from the labour market was defined as not working in the labour market when 61 years old or younger in 2010-2011. 

Results: Higher ERI OR=1.62 (95% CI 1.01 to 2.61, p=0.048) predicted exit from the labour market independent of age, sex, education, occupational class, allostatic load and depression. Job control OR=0.60 (95% CI 0.42 to 0.85, p=0.004) was associated with exit from the labour market independent of age, sex, education, occupation and depression. The association of higher effort OR=1.32 (95% CI 1.01 to 1.73, p=0.045) with exit from the labour market was independent of age, sex and depression but attenuated to non-significance when additionally controlling for socioeconomic measures. Reward was not related to exit from the labour market. 

Conclusions: Stressful work conditions can be a risk for exiting the labour market before the age of 61 years. Neither socioeconomic position nor allostatic load and depressive symptoms seem to explain this association.

An audit of antimicrobial treatment of lower respiratory and urinary tract infections in a hospital setting

Objectives: To audit the quality of treatment of lower respiratory tract infections (LRTIs) and urinary tract infections (UTIs) and to identify targets for antibiotic stewardship. Methods: The audit involved collecting data on admitted patients, who were diagnosed with LRTIs or UTIs and subsequently received antibiotic treatment (January 2009-April 2009). Key findings: The percentage adherence rate for hospital antibiotic policy was 68.6% (24/35). Documentation of the CURB-65 score was found in 80% (16/20) of the patients' clinical notes, for which 46.2% (6/13) of patients were treated according to their CURB- 65 score. The percentages of delayed and missed doses for all antibiotics were 21.7% (254/1171) and 8.6% (101/1171), respectively. The percentage of patients switched from intravenous to oral antibiotics in accordance with the policy was 58.5% (31/53). The mean length of stay for patients switched in line with the guidelines was 6.9 days (range: 2-18 days) compared with 13.2 days (range: 4-28 days) for patients treated with intravenous antibiotics >24 h after the intravenous to oral switch criteria were fulfilled; this equates to on average an extra 6.3 days of hospitalisation (p=0.01). Conclusions: The study identified a number of targets for quality improvement including adherence to antibiotic policy, documentation of the CURB-65 score in patients' notes and treating patients accordingly, addressing the issue of missed and delayed doses, and maintaining adherence to the hospital intravenous-to-oral antibiotic switch policy. The findings suggest that the quality of antibiotic prescribing could be improved by measuring and addressing such performance indicators.

Characterisation and modelling of the thermorheological properties of pharmaceutical polymers and their blends using capillary rheometry: Implications for hot melt processing of dosage forms.

Given the growing interest in thermal processing methods, this study describes the use of an advanced rheological technique, capillary rheometry, to accurately determine the thermorheological properties of two pharmaceutical polymers, Eudragit E100 (E100) and hydroxypropylcellulose JF (HPC) and their blends, both in the presence and absence of a model therapeutic agent (quinine, as the base and hydrochloride salt). Furthermore, the glass transition temperatures (Tg) of the cooled extrudates produced using capillary rheometry were characterised using Dynamic Mechanical Thermal Analysis (DMTA) thereby enabling correlations to be drawn between the information derived from capillary rheometry and the glass transition properties of the extrudates. The shear viscosities of E100 and HPC (and their blends) decreased as functions of increasing temperature and shear rates, with the shear viscosity of E100 being significantly greater than that of HPC at all temperatures and shear rates. All platforms were readily processed at shear rates relevant to extrusion (approximately 200–300 s−1) and injection moulding (approximately 900 s−1). Quinine base was observed to lower the shear viscosities of E100 and E100/HPC blends during processing and the Tg of extrudates, indicative of plasticisation at processing temperatures and when cooled (i.e. in the solid state). Quinine hydrochloride (20% w/w) increased the shear viscosities of E100 and HPC and their blends during processing and did not affect the Tg of the parent polymer. However, the shear viscosities of these systems were not prohibitive to processing at shear rates relevant to extrusion and injection moulding. As the ratio of E100:HPC increased within the polymer blends the effects of quinine base on the lowering of both shear viscosity and Tg of the polymer blends increased, reflecting the greater solubility of quinine within E100. In conclusion, this study has highlighted the importance of capillary rheometry in identifying processing conditions, polymer miscibility and plasticisation phenomena.

Lower resting energy expenditure and fat oxidation in Native American and Hispanic infants born to mothers with diabetes

OBJECTIVE: To determine whether exposure to diabetes in utero affects resting energy expenditure (REE) and fuel oxidation in infants.

STUDY DESIGN: At 35 ± 5 days after birth, body composition and REE were measured in full-term offspring of Native American and Hispanic women with either well-controlled diabetes (13 girls, 11 boys) or normal healthy pregnancies (18 girls, 17 boys).

RESULTS: Control of dysglycemia during gestation in the women with diabetes mellitus met current clinical standards, shown by average glycated hemoglobin (5.9 ± 0.2%; 40.6 ± 2.3 mmol/mol). Infant body mass (offspring of women with diabetes: 4.78 ± 0.13, control offspring: 4.56 ± 0.08 kg) and body fatness (offspring of women with diabetes: 25.2 ± 0.6, control offspring: 24.2 ± 0.5 %) did not differ between groups. REE, adjusted for lean body mass, was 14% lower in offspring of women with diabetes (41.7 ± 2.3 kJ/h) than control offspring (48.6 ± 2.0, P = .025). Fat oxidation was 26% lower in offspring of women with diabetes (0.54 ± 0.05 g/h) than control offspring (0.76 ± 0.04, P < .01) but carbohydrate oxidation did not differ. Thus, fat oxidation accounted for a lower fraction of REE in the offspring of women with diabetes (49 ± 4%) than control offspring (60 ± 3%, P = .022). Mothers with diabetes were older and had higher prepregnancy body mass index than control mothers.

CONCLUSIONS: Well-controlled maternal diabetes did not significantly affect body mass or composition of offspring at 1-month old. However, infants with mothers with diabetes had reduced REE and fat oxidation, which could contribute to adiposity and future disease risk. Further studies are needed to assess the impact differences in age and higher prepregnancy body mass index.

New lower Palaeolithic finds from the Axe valley Dorset

The Axe Valley has long been known for its Palaeolithic finds, particularly from the site at Broom. While research has continued at Broom, other sites have also been investigated in the valley as part of the English Heritage-managed and ALSFfunded project ?Palaeolithic Rivers of South West Britain? (PRoSWeB). This project was completed in March 2007. Since then, research focussing on the Quaternary geology and Palaeolithic archaeology of the southwest region has been continued at selected locations by Prof. Tony Brown (University of Southampton), Dr Laura Basell (University of Oxford) and Dr Phil Toms (University of Gloucestershire), with assistance from Dr Ramues Gallois and Dr Richard Scrivener (formerly British Geological Survey).

Biomineralization of Weathered Rock Rinds:Examples from the Lower Afroalpine Zone on Mount Kenya

Rock rinds have been used for half a century to date glacial deposits and recently inroads have been developed to use nuclides to provide absolute ages of weathering rinds in pebble clasts. Although maximum and minimum rind thicknesses have helped to elucidate time since deposition and allowed stratigraphic division of deposits at glacial rank, little has been done to investigate the wealth of mineral degradation, growth of alteration products and biomineralization that occur in these weathered crusts. In some cases the mass of microbe-mineral intergrowth is nearly present on a 50%/50% basis, with the biotic mass intergrown with mineral matter to such an extent that it probably controls pH and redox phenomena that act as accelerators in the weathering process. Assuming weathering time spans of 2 × 10⁶ years or more for a complete cycle, eventual clast decomposition is the end product. Here we present evidence of microbe-clast intergrowth from selected sites of Pleistocene age (~70 ka to 2.0 Ma) in the lower Afroalpine of Mt. Kenya and hypothesize about its role in rock decomposition and fossilization of biotic end-members. © 2013 Copyright Taylor and Francis Group, LLC.