Neutron diffraction of deuterated tripalmitin and the influence of shear on its crystallisation.

This neutron diffraction study of deuterated tripalmitin has provided further insight into a forensic observation of the crystallisation of lipids under high-shear conditions. To achieve this, an experimental set up was designed to enable simultaneous rheological data from a Couette cell to be recorded with neutron powder diffraction, enabling the influence of shear on the polymorph transformation on cooling to be monitored in real time. Tripalmitin was observed to directly transform from a liquid phase to a ß polymorph under the influence of shear. Although the liquid to ß transition was not observed to be influenced by shear rate, the degree of crystallinity, qualitatively denoted by an increase in the sharpness of the diffraction peaks, was observed at higher shear rates. Evidence is also presented that the rate of cooling influences the ordering in the ß-polymorph produced in zero shear conditions.

The strength of plants: theory and experimental methods to measure the mechanical properties of stems.

From the stems of agricultural crops to the structural trunks of trees, studying the mechanical behaviour of plant stems is critical for both commerce and science. Plant scientists are also increasingly relying on mechanical test data for plant phenotyping. Yet there are neither standardized methods nor systematic reviews of current methods for the testing of herbaceous stems. We discuss the architecture of plant stems and highlight important micro- and macrostructural parameters that need to be controlled and accounted for when designing test methodologies, or that need to be understood in order to explain observed mechanical behaviour. Then, we critically evaluate various methods to test structural properties of stems, including flexural bending (two-, three-, and four-point bending) and axial loading (tensile, compressive, and buckling) tests. Recommendations are made on best practices. This review is relevant to fundamental studies exploring plant biomechanics, mechanical phenotyping of plants, and the determinants of mechanical properties in cell walls, as well as to application-focused studies, such as in agro-breeding and forest management projects, aiming to understand deformation processes of stem structures. The methods explored here can also be extended to other elongated, rod-shaped organs (e.g. petioles, midribs, and even roots).

Viruses are frequently present as the infecting agent in acute exacerbations of chronic obstructive pulmonary disease in patients presenting to hospital.

BACKGROUND: Viral causes of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are well recognised but only recently have rapid tests become available. AIMS: To identify respiratory viruses in the general population and those associated with hospitalisation in AECOPD using polymerase chain reaction (PCR) on nasopharyngeal aspirate (NPA), and the relationship between symptoms, viral detection and inflammatory markers. METHODS: A review of viruses detected in the general population in a health district between August 2014 and July 2015, using multiplex PCR for viruses from NPA samples. In addition, a single hospital, retrospective audit of patients admitted with suspected AECOPD was conducted. RESULTS: Of the 8811 NPA tested, 5599 (64%) were positive for at least one virus and 2069 of these were obtained from adults. In adults, the most common viruses identified were Influenza A (31%), Rhinovirus (27%) and respiratory syncytial virus A/B (10%). Most patients with AECOPD (102 of 153) had NPA sent for viral PCR testing and 59 (58%) were positive. The most common viruses identified were Influenza A (31%), Rhinovirus (24%) and respiratory syncytial virus A/B (17%) with co-infecting bacteria cultured in 22 sputum samples. Patients with influenza-like symptoms were more likely to have a positive viral PCR than those without symptoms (P < 0.004). The median C-reactive protein on admission was lower in the virus-infected than uninfected AECOPD (28 vs 60 mg/L, P < 0.026). CONCLUSION: The spectrum of viruses detected in patients with AECOPD is similar to that of the general population. Viruses are more likely to be identified in patients with AECOPD who present with influenza-like symptoms and a low C-reactive protein.

Relationships between adult asthma and oxidative stress markers and pH in exhaled breath condensate: a systematic review.

Oxidative stress has a recognized role in the pathophysiology of asthma. Recently, interest has increased in the assessment of pH and airway oxidative stress markers. Collection of exhaled breath condensate (EBC) and quantification of biomarkers in breath samples can potentially indicate lung disease activity and help in the study of airway inflammation, and asthma severity. Levels of oxidative stress markers in the EBC have been systematically evaluated in children with asthma; however, there is no such systematic review conducted for adult asthma. A systematic review of oxidative stress markers measured in EBC of adult asthma was conducted, and studies were identified by searching MEDLINE and SCOPUS databases. Sixteen papers met the inclusion criteria. Concentrations of exhaled hydrogen ions, nitric oxide products, hydrogen peroxide and 8-isoprostanes were generally elevated and related to lower lung function tests in adults with asthma compared to healthy subjects. Assessment of EBC markers may be a noninvasive approach to evaluate airway inflammation, exacerbations, and disease severity of asthma, and to monitor the effectiveness of anti-inflammatory treatment regimens. Longitudinal studies, using standardized analytical techniques for EBC collection, are required to establish reference values for the interpretation of EBC markers in the context of asthma.

The efficacy of fluticasone furoate administered in the morning or evening is comparable in patients with persistent asthma.

BACKGROUND: The inhaled corticosteroid fluticasone furoate (FF) is efficacious as a once-daily treatment for the management of asthma. Asthma is associated with circadian changes, with worsening lung function at night. We compared the efficacy of once-daily FF in the morning or evening for the treatment of asthma. METHODS: Adults with persistent bronchial asthma were enrolled into this randomised, repeat-dose, double-blind, double-dummy, placebo-controlled, three-way crossover study. After a 14-day run-in period, patients received either: FF 100 µg in the morning (AM); FF 100 µg in the evening (PM); or placebo, via the ELLIPTA(®) dry powder inhaler. Patients received all three treatments (14 ± 2 day duration) separated by a 14- to 21-day washout period. The primary endpoint was 24-h weighted mean forced expiratory volume in 1 s (FEV1) measured at the end of each 14-day treatment. RESULTS: A total of 28 patients aged between 19 and 67 years were randomised and 21 (75%) completed all three study arms. Once-daily administration of FF 100 µg resulted in an increased 24-hour weighted mean FEV1; differences between the adjusted means for AM and PM FF dosing versus placebo were 0.077 L (90% confidence interval [CI]: 0.001, 0.152) and 0.105 L (90% CI: 0.029, 0.180), respectively (adjusted mean difference: -0.028 L [90% CI: -0.102, 0.045]). AM or PM doses had comparable incidences of adverse events (AEs; 18/23 versus 18/24, respectively), no serious AEs occurred. CONCLUSION: AM and PM doses of once-daily FF 100 µg produced comparable improvements in lung function relative to placebo.

Assessing the use of initial oxygen therapy in chronic obstructive pulmonary disease patients: a retrospective audit of pre-hospital and hospital emergency management.

BACKGROUND: Carbon dioxide retention in chronic obstructive pulmonary disease (COPD) exacerbations can be a complication of oxygen therapy. Current recommendations suggest an inspired oxygen level (FiO2 ) < 0.28, aiming for saturation (SpO2 ) of 88-92% until arterial blood gas analysis is available. AIMS: This study aims to assess the use of O2 therapy and FiO2 in the emergency management of patients with a known diagnosis of COPD. METHODS: Retrospective audit of 150 COPD patients admitted over 18 months, data being extracted from the hospital records. RESULTS: Of the records reviewed, 57% were male, mean age 75 years. COPD was recognised in 53%. SpO2 recorded in 124 patients, with SpO2 < 88% seen in 40 patients. Oxygen was administered in 123 patients in ambulances; high flow in 111 patients, and only 12 patients received O2 therapy in line with the recommended FiO2 < 0.28. In the emergency department (ED), 112 patients received O2 supplementation; high flow given in 68 patients. Hypercapnia was seen in 71 patients; FiO2 > 0.28 given in 54 patients in ambulances and in 35 patients in ED. Non-invasive ventilation was required in 53 patients; FiO2 > 0.28 given in 29 patients in the ED. Seven patients were admitted to intensive care unit, and 10 patients died. CONCLUSION: High-flow oxygen is used for the initial treatment of COPD exacerbations, but only 53% are recognised as having COPD. A FiO2 > 0.28 is often initiated before admission and continued in the ED. A larger study would be required to assess any possible harm of this approach, but education of those involved in the care of COPD patients may reduce the risk of complications of hypercapnia.

Safety, Feasibility, and Biomarker Effects of High-Dose Vitamin D Supplementation Among Women at High Risk for Breast Cancer.

Vitamin D deficiency is a potentially modifiable risk factor that may be targeted for breast cancer prevention. We examined the safety, feasibility, and biomarker effects of high-dose vitamin D among women at high risk for breast cancer. Forty high-risk women, defined as a 5-year breast cancer risk ≥1.67% per the Gail model, lobular or ductal carcinoma in situ, were assigned to a 1-year intervention of vitamin D3 20,000 IU or 30,000 IU weekly. Participants were monitored for toxicity every 3 months, underwent serial blood draws at baseline, 6 and 12 months, and a digital mammogram at baseline and 12 months. Biomarker endpoints included serum 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)2D], parathyroid hormone (PTH), insulin-like growth factor (IGF-1), IGF binding protein (IGFBP-3), and mammographic density (MD) using Cumulus software. From November 2007 to January 2011, we enrolled 40 women; 37 were evaluable at 6 months and 30 at 12 months. One patient was taken off study for hypercalciuria; otherwise, the intervention was well tolerated. From baseline to 12 months, mean serum 25(OH)D and 1,25(OH)2D rose from 20.0 to 46.9 ng/ml and 69.7 to 98.1 pg/ml, respectively (p<0.01). Serum PTH decreased by 12% at 6 months and IGF-1/IGFBP-3 ratio decreased by 4.3% at 12 months (p<0.05). There was no significant change in MD regardless of menopausal status or dose level. We demonstrated that 1 year of high-dose vitamin D3 was associated with a significant increase in circulating vitamin D levels and favorable effects on IGF signaling, but no significant change in MD.

Exhaled breath condensate in pediatric asthma: promising new advance or pouring cold water on a lot of hot air? a systematic review.

BACKGROUND: Exhaled breath condensate (EBC) analysis is a simple non-invasive technique that allows repeated collection of breath samples with a minimum of inconvenience for the subject. These breath samples can potentially indicate lung disease activity and given the ease of collection, EBC is becoming a useful research tool in the study of respiratory diseases. It has the potential to be used in both population-based studies and in the context of pediatric asthma it may prove useful in diagnosis and monitoring. METHODS: A systematic review was conducted to identify studies of EBC markers in childhood asthma. RESULTS: Most of the studies were cross-sectional in design, and the results suggest that simple chemical entities such as hydrogen ions (as pH), hydrogen peroxide, and oxides of nitrogen are associated with pediatric allergic asthma and exacerbations. In addition, more complex molecules including leukotrienes, prostaglandins, and cytokines such as the interleukins IL-4 and IL-5 are also elevated in the breath of those with asthma. CONCLUSION: EBC has the potential to aid diagnosis, and to evaluate the inflammatory status of asthmatic children. Future studies may be able to refine further how best to collect EBC samples, to interpret them, and the technique has the potential to allow repeated sampling which will allow studies of natural history, pathogenesis and response to treatment to be undertaken.

Comparison of quantification strategies for one-point standard addition calibration: the homoscedastic case.

Two quantification strategies for one-point standard addition calibration have been compared mathematically. One strategy involved the extrapolation of measurement points to their intercept with the x-axis to determine the analyte content in the unknown sample, and the other strategy is based upon direct calculation of the analyte content in the unknown sample using the instrumental responses obtained during measurement. The cases of both conventional standard addition calibration (C-SAC) and sequential standard addition calibration (S-SAC) have been considered. The homoscedastic situation has been considered, where the absolute precision of the instrumental response is constant. It has been determined that the precision ratio of the two strategies is dependent on surprisingly simple parameters: such as the sample to standard mass ratio (for C-SAC) and the analyte content ratio (for S-SAC).

Blocking the evolution of insecticide-resistant malaria vectors with a microsporidian.

Finding a way to block the evolution insecticide resistance would be a major breakthrough for the control of malaria. We suggest that this may be possible by introducing a stress into mosquito populations that restores the sensitivity of genetically resistant mosquitoes and that decreases their longevity when they are not exposed to insecticide. We use a mathematical model to show that, despite the intense selection pressure imposed by insecticides, moderate levels of stress might tip the evolutionary balance between costs and benefits of resistance toward maintaining sensitivity. Our experimental work with the microsporidian parasite Vavraia culicis infecting two lines of resistant mosquitoes and a sensitive line suggests that it may indeed be possible to stress the mosquitoes in the required way. The mortality of resistant mosquitoes 24 h after exposure to the insecticide was up to 8.8 times higher in infected than in uninfected ones; if mosquitoes were not exposed to the insecticide, resistant mosquitoes infected by the microsporidian lived about half as long as uninfected ones and insecticide-sensitive mosquitoes (with or without the parasite). Our results suggest that biopesticides or other insecticides that interfere with the expression of resistance may help to manage insecticide resistance in programs of malaria control.

Chest pain in asbestos and silica-exposed workers.

BACKGROUND: Chest pain may be the first symptom of developing respiratory malignancy, particularly in subjects with asbestos exposure, yet little information exists on this topic. AIMS: To investigate chest pain in a cohort of subjects exposed to asbestos and silica dust applying for compensation. METHODS: Cross-sectional study using a standardized questionnaire. Data collection included: smoking history, Medical Research Council scales of exercise capacity and respiratory symptoms. RESULTS: We studied 621 subjects. Six disease groups were categorized: asbestosis (n = 27), diffuse pleural thickening (DPT) (132), asbestosis and DPT (14), silicosis (26), pleural plaques only (160) and healthy subjects with a history of dust exposure (256). Crude prevalence rates of chest pain were high, with chest pain approximately twice as common in subjects with asbestos-related disorders and silicosis as in healthy subjects, with an overall frequency of ~40%. However, when other variables were taken into account in a multivariate analysis the differences between groups disappeared. The factor most significantly related to chest pain was age. CONCLUSIONS: Chest pain is apparently common in subjects with asbestos-related disorders and silicosis, but after adjustment for other variables, no increased prevalence was apparent in subjects with pleural disorders. More sophisticated questionnaires and dedicated imaging are required to elucidate this further.

Deficiency in the multicopy Sycp3-like X-linked genes Slx and Slxl1 causes major defects in spermatid differentiation.

The human and mouse sex chromosomes are enriched in multicopy genes required for postmeiotic differentiation of round spermatids into sperm. The gene Sly is present in multiple copies on the mouse Y chromosome and encodes a protein that is required for the epigenetic regulation of postmeiotic sex chromosome expression. The X chromosome carries two multicopy genes related to Sly: Slx and Slxl1. Here we investigate the role of Slx/Slxl1 using transgenically-delivered small interfering RNAs to disrupt their function. We show that Slx and Slxl1 are important for normal sperm differentiation and male fertility. Slx/Slxl1 deficiency leads to delay in spermatid elongation and sperm release. A high proportion of delayed spermatids are eliminated via apoptosis, with a consequent reduced sperm count. The remaining spermatozoa are abnormal with impaired motility and fertilizing abilities. Microarray analyses reveal that Slx/Slxl1 deficiency affects the metabolic processes occurring in the spermatid cytoplasm but does not lead to a global perturbation of sex chromosome expression; this is in contrast with the effect of Sly deficiency which leads to an up-regulation of X and Y chromosome genes. This difference may be due to the fact that SLX/SLXL1 are cytoplasmic while SLY is found in the nucleus and cytoplasm of spermatids.

An electronic nose in the discrimination of breath from smokers and non-smokers: a model for toxin exposure.

Exhaled breath contains hundreds of volatile organic compounds (VOCs) that may be used as non-invasive markers of lung disease. Electronic noses (e-noses) can analyse VOCs by composite nanosensor arrays with learning algorithms. This study investigated the use of an e-nose (Cyranose C320) to distinguish the breath of smokers from that of non-smokers. Smoking and non-smoking subjects exhaled from total lung capacity into a 2 L Tedlar bag and these samples were introduced offline to the e-nose in a random order. Two classes of breath, 'smoker' and 'non-smoker', were established and this model was then cross-validated. Principal component analysis then identified the maximal point of difference between classes. Smellprints of breath from smokers were separated from those of non-smokers (cross-validation value, 95%; Mahalanobis distance, 3.96). Subsequently, 15 smokers (mean age 37.9 ± 4.78 years, FEV(1) 3.15 ± 0.21 L), and 24 non-smokers (add mean age and FEV1 as for smokers) were sampled to revalidate the model. The e-nose correctly identified the smoking status in 37 of the 39 subjects. This demonstrates that the e-nose is simple to use in clinical practice and can differentiate the breath of smokers from that of non-smokers. It may prove to be a useful, non-invasive tool for further breath assessment of exposure to other inhaled noxious substances as well as disease monitoring.

Biomarkers in pulmonary hypertension.

There have been significant recent advances in the understanding of the pathophysiology of pulmonary hypertension, and a growing number of therapeutic agents have become available to the treating physician. Traditional methods of diagnosing and monitoring this condition have comprised echocardiography and right heart catheterisation, in addition to functional measures, such as estimation of functional class and the 6-min walk test. An increasing number of biomarkers have been described that are elevated in pulmonary hypertension and which may assist the clinician in diagnosis and in the assessment of disease severity and response to treatment. The present article details the more important biomarkers, their potential applications and the evidence supporting their use.

A spectroscopic investigation of the weathering of a heritage Sydney sandstone.

Infrared spectroscopy has been employed in a study of the degradation of heritage Sydney sandstone used in St. Mary's Cathedral in Sydney, Australia. Spectra were used to characterise the clay components taken from weathered and unweathered sandstone blocks removed from the Cathedral as part of a restoration programme. Two types of kaolin clays - kaolinite and its polymorph, dickite - have been identified. A higher amount of dickite present in the clay of weathered sandstone indicated that a kaolinite-to-dickite transformation occurs upon weathering. X-ray photoelectron spectroscopy was also used to confirm the presence of a more thermally stable polymorph of the kaolinite in the sandstone.