Connective tissue disease related interstitial lung diseases and idiopathic pulmonary fibrosis: provisional core sets of domains and instruments for use in clinical trials

Rationale Clinical trial design in interstitial lung diseases (ILDs) has been hampered by lack of consensus on appropriate outcome measures for reliably assessing treatment response. In the setting of connective tissue diseases (CTDs), some measures of ILD disease activity and severity may be confounded by non-pulmonary comorbidities. Methods The Connective Tissue Disease associated Interstitial Lung Disease (CTD-ILD) working group of Outcome Measures in Rheumatology—a non-profit international organisation dedicated to consensus methodology in identification of outcome measures—conducted a series of investigations which included a Delphi process including >248 ILD medical experts as well as patient focus groups culminating in a nominal group panel of ILD experts and patients. The goal was to define and develop a consensus on the status of outcome measure candidates for use in randomised controlled trials in CTD-ILD and idiopathic pulmonary fibrosis (IPF). Results A core set comprising specific measures in the domains of lung physiology, lung imaging, survival, dyspnoea, cough and health-related quality of life is proposed as appropriate for consideration for use in a hypothetical 1-year multicentre clinical trial for either CTD-ILD or IPF. As many widely used instruments were found to lack full validation, an agenda for future research is proposed. Conclusion Identification of consensus preliminary domains and instruments to measure them was attained and is a major advance anticipated to facilitate multicentre RCTs in the field

NS1 Specific CD8(+) T-Cells with Effector Function and TRBV11 Dominance in a Patient with Parvovirus B19 Associated Inflammatory Cardiomyopathy

Background: Parvovirus B19 (B19V) is the most commonly detected virus in endomyocardial biopsies (EMBs) from patients with inflammatory cardiomyopathy (DCMi). Despite the importance of T-cells in antiviral defense, little is known about the role of B19V specific T-cells in this entity. Methodology and Principal Findings: An exceptionally high B19V viral load in EMBs (115,091 viral copies/mg nucleic acids), peripheral blood mononuclear cells (PBMCs) and serum was measured in a DCMi patient at initial presentation, suggesting B19V viremia. The B19V viral load in EMBs had decreased substantially 6 and 12 months afterwards, and was not traceable in PBMCs and the serum at these times. Using pools of overlapping peptides spanning the whole B19V proteome, strong CD8(+) T-cell responses were elicited to the 10-amico-acid peptides SALKLAIYKA (19.7% of all CD8(+) cells) and QSALKLAIYK (10%) and additional weaker responses to GLCPHCINVG (0.71%) and LLHTDFEQVM (0.06%). Real-time RT-PCR of IFN gamma secretion-assay-enriched T-cells responding to the peptides, SALKLAIYKA and GLCPHCINVG, revealed a disproportionately high T-cell receptor Vbeta (TRBV) 11 expression in this population. Furthermore, dominant expression of type-1 (IFN gamma, IL2, IL27 and Tbet) and of cytotoxic T-cell markers (Perforin and Granzyme B) was found, whereas gene expression indicating type-2 (IL4, GATA3) and regulatory T-cells (FoxP3) was low. Conclusions: Our results indicate that B19V Ag-specific CD8(+) T-cells with effector function are involved in B19V associated DCMi. In particular, a dominant role of TRBV11 and type-1/CTL effector cells in the T-cell mediated antiviral immune response is suggested. The persistence of B19V in the endomyocardium is a likely antigen source for the maintenance of CD8(+) T-cell responses to the identified epitopes

Facile Fabrication of Uniform Polyaniline Nanotubes with Tubular Aluminosilicates as Templates

The uniform polyaniline (PANI) nanotubes, with inner diameter, outer diameter, and tubular thickness of 40, 60, and 10 nm, respectively, were prepared successfully by using natural tubular aluminosilicates as templates. The halloysite nanotubes were coated with PANI via the in situ chemical oxidation polymerization. Then the templates were etched with HCl/HF solution. The PANI nanotubes were characterized using FTIR, X-ray diffraction, and transmission electron microscopy. The conductivity of the PANI nanotubes was found to be 1.752 × 10−5(Ω·cm)−1

Phosphorus and Calcium

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142245/1/ncp0021.pd

Multiscale models for movement in oriented environments and their application to hilltopping in butterflies

Hilltopping butterflies direct their movement in response to topography, facilitating mating encounters via accumulation at summits. In this paper, we take hilltopping as a case study to explore the impact of complex orienteering cues on population dynamics. The modelling employs a standard multiscale framework, in which an individual's movement path is described as a stochastic 'velocity-jump' process and scaling applied to generate a macroscopic model capable of simulating large populations in landscapes. In this manner, the terms and parameters of the macroscopic model directly relate to statistical inputs of the individual-level model (mean speeds, turning rates and turning distributions). Applied to hilltopping in butterflies, we demonstrate how hilltopping acts to aggregate populations at summits, optimising mating for low-density species. However, for abundant populations, hilltopping is not only less effective but also possibly disadvantageous, with hilltopping males recording a lower mating rate than their non-hilltopping competitors. © 2013 Springer Science+Business Media Dordrecht

Investigation on the Plasma-Induced Emission Properties of Large Area Carbon Nanotube Array Cathodes with Different Morphologies

Large area well-aligned carbon nanotube (CNT) arrays with different morphologies were synthesized by using a chemical vapor deposition. The plasma-induced emission properties of CNT array cathodes with different morphologies were investigated. The ratio of CNT height to CNT-to-CNT distance has considerable effects on their plasma-induced emission properties. As the ratio increases, emission currents of CNT array cathodes decrease due to screening effects. Under the pulse electric field of about 6 V/μm, high-intensity electron beams of 170–180 A/cm2 were emitted from the surface plasma. The production mechanism of the high-intensity electron beams emitted from the CNT arrays was plasma-induced emission. Moreover, the distribution of the electron beams was in situ characterized by the light emission from the surface plasma

Of gastro and the gold standard: evaluation and policy implications of norovirus test performance for outbreak detection

<p>Abstract</p> <p>Background</p> <p>The norovirus group (NVG) of caliciviruses are the etiological agents of most institutional outbreaks of gastroenteritis in North America and Europe. Identification of NVG is complicated by the non-culturable nature of this virus, and the absence of a diagnostic gold standard makes traditional evaluation of test characteristics problematic.</p> <p>Methods</p> <p>We evaluated 189 specimens derived from 440 acute gastroenteritis outbreaks investigated in Ontario in 2006–07. Parallel testing for NVG was performed with real-time reverse-transcriptase polymerase chain reaction (RT²-PCR), enzyme immunoassay (EIA) and electron microscopy (EM). Test characteristics (sensitivity and specificity) were estimated using latent class models and composite reference standard methods. The practical implications of test characteristics were evaluated using binomial probability models.</p> <p>Results</p> <p>Latent class modelling estimated sensitivities of RT²-PCR, EIA, and EM as 100%, 86%, and 17% respectively; specificities were 84%, 92%, and 100%; estimates obtained using a composite reference standard were similar. If all specimens contained norovirus, RT²-PCR or EIA would be associated with > 99.9% likelihood of at least one test being positive after three specimens tested. Testing of more than 5 true negative specimens with RT²-PCR would be associated with a greater than 50% likelihood of a false positive test.</p> <p>Conclusion</p> <p>Our findings support the characterization of EM as lacking sensitivity for NVG outbreaks. The high sensitivity of RT²-PCR and EIA permit identification of NVG outbreaks with testing of limited numbers of clinical specimens. Given risks of false positive test results, it is reasonable to limit the number of specimens tested when RT²-PCR or EIA are available.</p

Forming a three-dimensional porous organic network via solid-state explosion of organic single crystals

Solid-state reaction of organic molecules holds a considerable advantage over liquid-phase processes in the manufacturing industry. However, the research progress in exploring this benefit is largely staggering, which leaves few liquid-phase systems to work with. Here, we show a synthetic protocol for the formation of a three-dimensional porous organic network via solid-state explosion of organic single crystals. The explosive reaction is realized by the Bergman reaction (cycloaromatization) of three enediyne groups on 2,3,6,7,14,15-hexaethynyl-9,10-dihydro-9,10-[1,2]benzenoanthracene. The origin of the explosion is systematically studied using single-crystal X-ray diffraction and differential scanning calorimetry, along with high-speed camera and density functional theory calculations. The results suggest that the solid-state explosion is triggered by an abrupt change in lattice energy induced by release of primer molecules in the 2,3,6,7,14,15-hexaethynyl-9,10-dihydro-9,10-[1,2]benzenoanthracene crystal lattice

Digital clubbing in tuberculosis – relationship to HIV infection, extent of disease and hypoalbuminemia

BACKGROUND: Digital clubbing is a sign of chest disease known since the time of Hippocrates. Its association with tuberculosis (TB) has not been well studied, particularly in Africa where TB is common. The prevalence of clubbing in patients with pulmonary TB and its association with Human Immunodeficiency Virus (HIV), severity of disease, and nutritional status was assessed. METHODS: A cross-sectional study was carried out among patients with smear-positive TB recruited consecutively from the medical and TB wards and outpatient clinics at a public hospital in Uganda. The presence of clubbing was assessed by clinical signs and measurement of the ratio of the distal and inter-phalangeal diameters (DPD/IPD) of both index fingers. Clubbing was defined as a ratio > 1.0. Chest radiograph, serum albumin and HIV testing were done. RESULTS: Two hundred patients (82% HIV-infected) participated; 34% had clubbing by clinical criteria whilst 30% had clubbing based on DPD/IPD ratio. Smear grade, extensive or cavitary disease, early versus late HIV disease, and hypoalbuminemia were not associated with clubbing. Clubbing was more common among patients with a lower Karnofsky performance scale score or with prior TB. CONCLUSION: Clubbing occurs in up to one-third of Ugandan patients with pulmonary TB. Clubbing was not associated with stage of HIV infection, extensive disease or hypoalbuminemia

SLO-2 Is Cytoprotective and Contributes to Mitochondrial Potassium Transport

Mitochondrial potassium channels are important mediators of cell protection against stress. The mitochondrial large-conductance “big” K+ channel (mBK) mediates the evolutionarily-conserved process of anesthetic preconditioning (APC), wherein exposure to volatile anesthetics initiates protection against ischemic injury. Despite the role of the mBK in cardioprotection, the molecular identity of the channel remains unknown. We investigated the attributes of the mBK using C. elegans and mouse genetic models coupled with measurements of mitochondrial K+ transport and APC. The canonical Ca2+-activated BK (or “maxi-K”) channel SLO1 was dispensable for both mitochondrial K+ transport and APC in both organisms. Instead, we found that the related but physiologically-distinct K+ channel SLO2 was required, and that SLO2-dependent mitochondrial K+ transport was triggered directly by volatile anesthetics. In addition, a SLO2 channel activator mimicked the protective effects of volatile anesthetics. These findings suggest that SLO2 contributes to protection from hypoxic injury by increasing the permeability of the mitochondrial inner membrane to K+