Treatment of Advanced Emphysema with Emphysematous Lung Sealant (AeriSeal (R))

Background: This report summarizes initial tests of an emphysematous lung synthetic polymer sealant (ELS) designed to reduce lung volume in patients with advanced emphysema. Objectives: The primary study objective was to define a therapeutic strategy to optimize treatment safety and effectiveness. Methods: ELS therapy was administered bronchoscopically to 25 patients with heterogeneous emphysema in an open-label, noncontrolled study at 6 centers in Germany. Treatment was performed initially at 2-4 subsegments. After 12 weeks, patients were eligible for repeat therapy to a total of 6 sites. Safety and efficacy were assessed after 6 months. Responses were evaluated in terms of changes from baseline in lung physiology, functional capacity, and health-related quality of life. Follow-up is available for 21 of 25 patients. Results: Treatment was well tolerated. There were no treatment-related deaths (i.e. within 90 days of treatment), and an acceptable short-and long-term safety profile. Physiological and clinical benefits were observed at 24 weeks. Efficacy responses were better among Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage III patients {[}n = 14; change in residual volume/total lung capacity (Delta RV/TLC) = -7.4 +/- 10.3%; Delta forced expiratory volume in 1 s (Delta FEV(1)) = +15.9 +/- 22.6%; change in forced vital capacity (Delta FVC) = +24.1 +/- 22.7%; change in carbon monoxide lung diffusion capacity (Delta DLCO) = +19.3 +/- 34.8%; change in 6-min walk test (Delta 6MWD) = +28.7 +/- 59.6 m; change in Medical Research Council Dyspnea (Delta MRCD) score = -1.0 +/- 1.04 units; change in St. George's Respiratory Questionnaire (Delta SGRQ) score = -9.9 +/- 15.3 units] than for GOLD stage IV patients (n = 7; Delta RV/TLC = -0.5 +/- 6.4%; Delta FEV 1 = +2.3 +/- 12.3%; Delta FVC = +2.6 +/- 21.1%; Delta DLCO = -2.8 +/- 17.2%; Delta 6MWD = +28.3 +/- 58.4 m; Delta MRCD = 0.3 +/- 0.81 units; Delta SGRQ = -6.7 +/- 7.0 units). Conclusions: ELS therapy shows promise for treating patients with advanced heterogeneous emphysema. Additional studies to assess responses in a larger cohort with a longer follow-up are warranted. Copyright (C) 2011 S. Karger AG, Base

Additive manufacture of three dimensional nanocomposite based objects through multiphoton fabrication

Three dimensional structures prepared from a gold-polymer composite formulation have been fabricated using multiphoton lithography. In this process, gold nanoparticles were simultaneously formed through photoreduction whilst polymerisation of two possible monomers was promoted. The monomers, trimethylopropane triacrylate (TMPTA) and pentaerythritol triacrylate (PETA) were mixed with a gold salt, but it was found that the addition of a Ruthenium (II) complex enhanced both the geometrical uniformity and integrity of the polymerized / reduced material, enabling the first production of 3D gold-polymer structures by single step multiphoton lithography

Three dimensional ink-jet printing of biomaterials using ionic liquids and co-solvents

1-Ethyl-3-methylimidazolium acetate ([C2C1Im][OAc]) and 1-butyl-3-methylimidazolium acetate ([C4C1Im][OAc]) have been used as solvents for the dissolution and ink-jet printing of cellulose from 1.0 to 4.8 wt%, mixed with the co-solvents 1-butanol and DMSO. 1-Butanol and DMSO were used as rheological modifiers to ensure consistent printing, with DMSO in the range of 41–47 wt% producing samples within the printable range of a DIMATIX print-head used (printability parameter < 10) at 55 °C, whilst maintaining cellulose solubility. Regeneration of cellulose from printed samples using water was demonstrated, with the resulting structural changes to the cellulose sample assessed by scanning electron microscopy (SEM) and white light interferometry (WLI). These results indicate the potential of biorenewable materials to be used in the 3D additive manufacture process to generate single-component and composite materials

Superconductivity close to the Mott state: From condensed-matter systems to superfluidity in optical lattices

Since the discovery of high-temperature superconductivity in 1986 by Bednorz and Mueller, great efforts have been devoted to finding out how and why it works. From the d-wave symmetry of the order parameter, the importance of antiferromagnetic fluctuations, and the presence of a mysterious pseudogap phase close to the Mott state, one can conclude that high-Tc superconductors are clearly distinguishable from the well-understood BCS superconductors. The d-wave superconducting state can be understood through a Gutzwiller-type projected BCS wave-function. In this review article, we revisit the Hubbard model at half-filling and focus on the emergence of exotic superconductivity with d-wave symmetry in the vicinity of the Mott state, starting from ladder systems and then studying the dimensional crossovers to higher dimensions. This allows to confirm that short-range antiferromagnetic fluctuations can mediate superconductivity with d-wave symmetry. Ladders are also nice prototype systems allowing to demonstrate the truncation of the Fermi surface and the emergence of a Resonating Valence Bond (RVB) state with preformed pairs in the vicinity of the Mott state. In two dimensions, a similar scenario emerges from renormalization group arguments. We also discuss theoretical predictions for the d-wave superconducting phase as well as the pseudogap phase, and address the crossover to the overdoped regime. Finally, cold atomic systems with tunable parameters also provide a complementary insight into this outstanding problem.Comment: 98 pages and 18 figures; Final version (references added and misprints corrected

3D reactive inkjet printing of polydimethylsiloxane

Material jetting is a process whereby liquid material can be deposited onto a substrate to solidify. Through a process of progressive additional layers, this deposition can then be used to produce 3D structures. However, the current material jetting catalogue is limited owing to the constraints on the viscosity of inks that can be deposited. Most inks currently being used are either solvent or photocuring based, with the latter becoming increasingly popular due to increased throughput. Full Reactive Inkjet Printing (FRIJP) is an alternative processing method currently being investigated as a route to widen the material catalogue. FRIJP is the combination, on the substrate, of two reactive components which then react together in contact on the substrate. In this work a two-part polydimethylsiloxane (PDMS) ink has been developed, printed individually, and cured. The successful printing of PDMS has been used to fabricate complex 3D geometry for the first time using FRIJP. Through the use of a prepared substrate feature resolutions up to 48 ± 2 μm (X, Y) were possible. Curing analysis has been conducted. It was found that not only does the reaction occur to a similar degree to conventional processes, but that there is no variation in the cured sample when printed at elevated substrate temperatures

Optimised laser microdissection of the human ocular surface epithelial regions for microarray studies

Background The most important challenge of performing insitu transcriptional profiling of the human ocular surface epithelial regions is obtaining samples in sufficient amounts, without contamination from adjacent tissue, as the region of interest is microscopic and closely apposed to other tissues regions. We have effectively collected ocular surface (OS) epithelial tissue samples from the Limbal Epithelial Crypt (LEC), limbus, cornea and conjunctiva of post-mortem cadaver eyes with laser microdissection (LMD) technique for gene expression studies with spotted oligonucleotide microarrays and Gene 1.0 ST arrays. Methods Human donor eyes (4 pairs for spotted oligonucleotide microarrays, 3 pairs for Gene 1.0 ST arrays) consented for research were included in this study with due ethical approval of the Nottingham Research Ethics Committee. Eye retrieval was performed within 36 hours of post-mortem period. The dissected corneoscleral buttons were immersed in OCT media and frozen in liquid nitrogen and stored at −80°C till further use. Microscopic tissue sections of interest were taken on PALM slides and stained with Toluidine Blue for laser microdissection with PALM microbeam systems. Optimisation of the laser microdissection technique was crucial for efficient and cost effective sample collection. Results The starting concentration of RNA as stipulated by the protocol of microarray platforms was taken as the cut-off concentration of RNA samples in our studies. The area of LMD tissue processed for spotted oligonucleotide microarray study ranged from 86,253 μm2 in LEC to 392,887 μm2 in LEC stroma. The RNA concentration of the LMD samples ranged from 22 to 92 pg/μl. The recommended starting concentration of the RNA samples used for Gene 1.0 ST arrays was 6 ng/5 μl. To achieve the desired RNA concentration the area of ocular surface epithelial tissue sample processed for the Gene 1.0 ST array experiments was approximately 100,0000 μm2 to 130,0000 μm2. RNA concentration of these samples ranged from 10.88 ng/12 μl to 25.8 ng/12 μl, with the RNA integrity numbers (RIN) for these samples from 3.3 to 7.9. RNA samples with RIN values below 2, that had failed to amplify satisfactorily were discarded. Conclusions The optimised protocol for sample collection and laser microdissection improved the RNA yield of the insitu ocular surface epithelial regions for effective microarray studies on spotted oligonucleotide and affymetrix platforms

Pulmonary rehabilitation following exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Guidelines have provided positive recommendations for pulmonary rehabilitation after exacerbations of chronic obstructive pulmonary disease (COPD), but recent studies indicate that postexacerbation rehabilitation may not always be effective in patients with unstable COPD. OBJECTIVES: To assess effects of pulmonary rehabilitation after COPD exacerbations on hospital admissions (primary outcome) and other patient-important outcomes (mortality, health-related quality of life (HRQL) and exercise capacity). SEARCH METHODS: We identified studies through searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PEDro (Physiotherapy Evidence Database) and the Cochrane Airways Review Group Register of Trials. Searches were current as of 20 October 2015, and handsearches were run up to 5 April 2016. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing pulmonary rehabilitation of any duration after exacerbation of COPD versus conventional care. Pulmonary rehabilitation programmes had to include at least physical exercise (endurance or strength exercise, or both). We did not apply a criterion for the minimum number of exercise sessions a rehabilitation programme had to offer to be included in the review. Control groups received conventional community care without rehabilitation. DATA COLLECTION AND ANALYSIS: We expected substantial heterogeneity across trials in terms of how extensive rehabilitation programmes were (i.e. in terms of number of completed exercise sessions; type, intensity and supervision of exercise training; and patient education), duration of follow-up (< 3 months vs ≥ 3 months) and risk of bias (generation of random sequence, concealment of random allocation and blinding); therefore, we performed subgroup analyses that were defined before we carried them out. We used standard methods expected by Cochrane in preparing this update, and we used GRADE for assessing the quality of evidence. MAIN RESULTS: For this update, we added 11 studies and included a total of 20 studies (1477 participants). Rehabilitation programmes showed great diversity in terms of exercise training (number of completed exercise sessions; type, intensity and supervision), patient education (from none to extensive self-management programmes) and how they were organised (within one setting, e.g. pulmonary rehabilitation, to across several settings, e.g. hospital, outpatient centre and home). In eight studies, participants completed extensive pulmonary rehabilitation, and in 12 studies, participants completed pulmonary rehabilitation ranging from not extensive to moderately extensive.Eight studies involving 810 participants contributed data on hospital readmissions. Moderate-quality evidence indicates that pulmonary rehabilitation reduced hospital readmissions (pooled odds ratio (OR) 0.44, 95% confidence interval (CI) 0.21 to 0.91), but results were heterogenous (I(2) = 77%). Extensiveness of rehabilitation programmes and risk of bias may offer an explanation for the heterogeneity, but subgroup analyses were not statistically significant (P values for subgroup effects were between 0.07 and 0.11). Six studies including 670 participants contributed data on mortality. The quality of evidence was low, and the meta-analysis did not show a statistically significant effect of rehabilitation on mortality (pooled OR 0.68, 95% CI 0.28 to 1.67). Again, results were heterogenous (I(2) = 59%). Subgroup analyses showed statistically significant differences in subgroup effects between trials with more and less extensive rehabilitation programmes and between trials at low and high risk for bias, indicating possible explanations for the heterogeneity. Hospital readmissions and mortality studies newly included in this update showed, on average, significantly smaller effects of rehabilitation than were seen in earlier studies.High-quality evidence suggests that pulmonary rehabilitation after an exacerbation improves health-related quality of life. The eight studies that used St George's Respiratory Questionnaire (SGRQ) reported a statistically significant effect on SGRQ total score, which was above the minimal important difference (MID) of four points (mean difference (MD) -7.80, 95% CI -12.12 to -3.47; I(2) = 64%). Investigators also noted statistically significant and important effects (greater than MID) for the impact and activities domains of the SGRQ. Effects were not statistically significant for the SGRQ symptoms domain. Again, all of these analyses showed heterogeneity, but most studies showed positive effects of pulmonary rehabilitation, some studies showed large effects and others smaller but statistically significant effects. Trials at high risk of bias because of lack of concealment of random allocation showed statistically significantly larger effects on the SGRQ than trials at low risk of bias. High-quality evidence shows that six-minute walk distance (6MWD) improved, on average, by 62 meters (95% CI 38 to 86; I(2) = 87%). Heterogeneity was driven particularly by differences between studies showing very large effects and studies showing smaller but statistically significant effects. For both health-related quality of life and exercise capacity, studies newly included in this update showed, on average, smaller effects of rehabilitation than were seen in earlier studies, but the overall results of this review have not changed to an important extent compared with results reported in the earlier version of this review.Five studies involving 278 participants explicitly recorded adverse events, four studies reported no adverse events during rehabilitation programmes and one study reported one serious event. AUTHORS' CONCLUSIONS: Overall, evidence of high quality shows moderate to large effects of rehabilitation on health-related quality of life and exercise capacity in patients with COPD after an exacerbation. Some recent studies showed no benefit of rehabilitation on hospital readmissions and mortality and introduced heterogeneity as compared with the last update of this review. Such heterogeneity of effects on hospital readmissions and mortality may be explained to some extent by the extensiveness of rehabilitation programmes and by the methodological quality of the included studies. Future researchers must investigate how the extent of rehabilitation programmes in terms of exercise sessions, self-management education and other components affects the outcomes, and how the organisation of such programmes within specific healthcare systems determines their effects after COPD exacerbations on hospital readmissions and mortality

Century-Long Increasing Trend and Variability of Dissolved Organic Carbon Export from the Mississippi River Basin Driven by Natural and Anthropogenic Forcing

There has been considerable debate as to how natural forcing and anthropogenic activities alter the timing and magnitude of the delivery of dissolved organic carbon (DOC) to the coastal ocean, which has ramifications for the ocean carbon budget, land-ocean interactions, and coastal life. Here we present an analysis of DOC export from the Mississippi River to the Gulf of Mexico during 1901–2010 as influenced by changes in climate, land use and management practices, atmospheric CO2, and nitrogen deposition, through the integration of observational data with a coupled hydrologic/biogeochemical land model. Model simulations show that DOC export in the 2000s increased more than 40% since the 1900s. For the recent three decades (1981–2010), however, our simulated DOC export did not show a significant increasing trend, which is consistent with observations by U.S. Geological Survey. Our factorial analyses suggest that land use and land cover change, including land management practices (LMPs: i.e., fertilization, irrigation, tillage, etc.), were the dominant contributors to the century-scale trend of rising total riverine DOC export, followed by changes in atmospheric CO2, nitrogen deposition, and climate. Decadal and interannual variations of DOC export were largely attributed to year-to-year climatic variability and extreme flooding events, which have been exacerbated by human activity. LMPs show incremental contributions to DOC increase since the 1960s, indicating the importance of sustainable agricultural practices in coping with future environmental changes such as extreme flooding events. Compared to the observational-based estimate, the modeled DOC export was 20% higher, while DOC concentrations were slightly lower. Further refinements in model structure and input data sets should enable reductions in uncertainties in our prediction of century-long trends in DOC

Traditions of research into interruptions in healthcare: A conceptual review

Background Researchers from diverse theoretical backgrounds have studied workplace interruptions in healthcare, leading to a complex and conflicting body of literature. Understanding pre-existing viewpoints may advance the field more effectively than attempts to remove bias from investigations. Objective To identify research traditions that have motivated and guided interruptions research, and to note research questions posed, gaps in approach, and possible avenues for future research. Methods A critical review was conducted of research on interruptions in healthcare. Two researchers identified core research communities based on the community’s motivations, philosophical outlook, and methods. Among the characteristics used to categorise papers into research communities were the predominant motivation for studying interruptions, the research questions posed, and key contributions to the body of knowledge on interruptions in healthcare. In cases where a paper approached an equal number of characteristics from two traditions, it was placed in a blended research community. Results A total of 141 papers were identified and categorised; all papers identified were published from 1994 onwards. Four principal research communities emerged: epidemiology, quality improvement, cognitive systems engineering (CSE), and applied cognitive psychology. Blends and areas of mutual influence between the research communities were identified that combine the benefits of individual traditions, but there was a notable lack of blends incorporating quality improvement initiatives. The question most commonly posed by researchers across multiple communities was: what is the impact of interruptions? Impact was measured as a function of task time or risk in the epidemiology tradition, situation awareness in the CSE tradition, or resumption lag (time to resume an interrupted task) in the applied cognitive psychology tradition. No single question about interruptions in healthcare was shared by all four of the core communities. Conclusions Much research on workplace interruptions in healthcare can be described in terms of fundamental values of four distinct research traditions and the communities that bring the values and methods: of those research traditions to their investigations. Blends between communities indicate that mutual influence has occurred as interruptions research has progressed. It is clear from this review that there is no single or privileged perspective to study interruptions. Instead, these findings suggest that researchers investigating interruptions in healthcare would benefit from being more aware of different perspectives from their own, especially when they consider workplace interventions to reduce interruptions

Climate Extremes Dominating Seasonal and Interannual Variations in Carbon Export from the Mississippi River Basinariations in Carbon Export from the Mississippi River Basin

Knowledge about the annual and seasonal patterns of organic and inorganic carbon (C) exports from the major rivers of the world to the coastal ocean is essential for our understanding and potential management of the global C budget so as to limit anthropogenic modification of global climate. Unfortunately our predictive understanding of what controls the timing, magnitude, and quality of C export is still rudimentary. Here we use a process-based coupled hydrologic/ecosystem biogeochemistry model (the Dynamic Land Ecosystem Model) to examine how climate variability and extreme events, changing land use, and atmospheric chemistry have affected the annual and seasonal patterns of C exports from the Mississippi River basin to the Gulf of Mexico. Our process-based simulations estimate that the average annual exports of dissolved organic C (DOC), particulate organic C (POC), and dissolved inorganic C (DIC) in the 2000s were 2.6 ± 0.4 Tg C yr−1, 3.4 ± 0.3 Tg C yr−1, and 18.8 ± 3.4 Tg C yr−1, respectively. Although land use change was the most important agent of change in C export over the past century, climate variability and extreme events (such as flooding and drought) were primarily responsible for seasonal and interannual variations in C export from the basin. The maximum seasonal export of DIC occurred in summer while for DOC and POC the maximum occurred in winter. Relative to the 10 year average (2001–2010), our modeling analysis indicates that the years of maximal and minimal C export cooccurred with wet and dry years (2008: 32% above average and 2006: 32% below average). Given Intergovernmental Panel on Climate Change-predicted changes in climate variability and the severity of rain events and droughts of wet and dry years for the remainder of the 21st century, our modeling results suggest major changes in the riverine link between the terrestrial and oceanic realms, which are likely to have a major impact on C delivery to the coastal ocean