Investigating the relationship between peak inspiratory flow rate and volume of inhalation from a Diskus™ Inhaler and baseline spirometric parameters: a cross-sectional study

Drug delivery from a Dry Powder Inhaler (DPI) is dependent on the peak inspiratory flow rate (PIFR) generated. Currently available methods for estimating PIFR from most DPIs are limited and mainly rely on subjective assessment. We aim to show that spirometric and Diskus™ PIFR and Inspiratory Vital Capacity (IVC) are related to the underlying respiratory condition and that spirometric PIFR can be used to assess whether Diskus™ PIFR will be adequate when using this DPI. Healthy volunteers and patients with asthma, COPD, neuromuscular disease and non-respiratory disorders were recruited (n = 85). Demographics and baseline lung function by spirometry were recorded. Flow and volume readings were taken while patients used a Diskus™ DPI, housed in an airtight container connected to a spirometer. T-tests were performed to compare mean spirometric and Diskus™ PIFR/ IVC between groups. Stepwise regression analysis of Diskus™ PIFR versus spirometric PIFR, spirometric IVC, age, gender, condition, BMI, FEV1 and FVC was performed. The Diskus™ PIFR for the COPD and Neuromuscular Disease group was more than 10 L/min lower than the Healthy or Asthma groups (p \u3c 0.05). The mean spirometric and Diskus™ IVC of the Healthy group was significantly (\u3e0.75 L) higher than the mean for the other three groups (p \u3c 0.05). Diskus™ PIFR was moderately correlated with spirometric PIFR and age (Adjusted R2 = 0.58, p \u3c 0.0001). PIFR generated using a Diskus™ DPI is dependent on the underlying disease and age. A spirometric PIFR of less than 196 L/min should prompt further investigation into the suitability of a patient for a Diskus™ DPI, with possible consideration of alternate devices

The furan microsolvation blind challenge for quantum chemical methods: First steps

© 2018 Author(s). Herein we present the results of a blind challenge to quantum chemical methods in the calculation of dimerization preferences in the low temperature gas phase. The target of study was the first step of the microsolvation of furan, 2-methylfuran and 2,5-dimethylfuran with methanol. The dimers were investigated through IR spectroscopy of a supersonic jet expansion. From the measured bands, it was possible to identify a persistent hydrogen bonding OH-O motif in the predominant species. From the presence of another band, which can be attributed to an OH-π interaction, we were able to assert that the energy gap between the two types of dimers should be less than or close to 1 kJ/mol across the series. These values served as a first evaluation ruler for the 12 entries featured in the challenge. A tentative stricter evaluation of the challenge results is also carried out, combining theoretical and experimental results in order to define a smaller error bar. The process was carried out in a double-blind fashion, with both theory and experimental groups unaware of the results on the other side, with the exception of the 2,5-dimethylfuran system which was featured in an earlier publication

The nature of the high Galactic latitude O-star HD93521: new results from X-ray and optical spectroscopy

Owing to its unusual location and its isolation, the nature of the high Galactic latitude O9.5Vp object HD93521 is still uncertain. We have collected X-ray and optical observations to characterize the star and its surroundings. X-ray images and spectra are analyzed to search for traces of a recent star formation event around HD93521 and to search for the signature of a possible compact companion. Optical echelle spectra are analysed with plane-parallel model atmosphere codes, assuming either a spherical star or a gravity darkened rotationally flattened star, to infer the effective temperature and surface gravity, and to derive the He, C, N and O abundances of HD93521. The X-ray images reveal no traces of a population of young low-mass stars coeval with HD93521. The X-ray spectrum of HD93521 is consistent with a normal late O-type star although with subsolar metallicity. No trace of a compact companion is found in the X-ray data. In the optical spectrum, He and N are found to be overabundant, in line with the effect of rotational mixing in this very fast rotator, whilst C and O are subsolar. A critical comparison with the properties of subdwarf OB stars, indicates that, despite some apparent similarities, HD93521 does not belong to this category. Despite some ambiguities on the runaway status of the star, the most likely explanation is that HD93521 is a Population I massive O-type star that was ejected from the Galactic plane either through dynamical interactions or a result of a supernova event in a binary system.Comment: Accepted for publication in Astronomy & Astrophysic

Perturbation with Intrabodies Reveals That Calpain Cleavage Is Required for Degradation of Huntingtin Exon 1

Background: Proteolytic processing of mutant huntingtin (mHtt), the protein that causes Huntington's disease (HD), is critical for mHtt toxicity and disease progression. mHtt contains several caspase and calpain cleavage sites that generate N-terminal fragments that are more toxic than full-length mHtt. Further processing is then required for the degradation of these fragments, which in turn, reduces toxicity. This unknown, secondary degradative process represents a promising therapeutic target for HD. Methodology/Principal Findings: We have used intrabodies, intracellularly expressed antibody fragments, to gain insight into the mechanism of mutant huntingtin exon 1 (mHDx-1) clearance. Happ1, an intrabody recognizing the proline-rich region of mHDx-1, reduces the level of soluble mHDx-1 by increasing clearance. While proteasome and macroautophagy inhibitors reduce turnover of mHDx-1, Happ1 is still able to reduce mHDx-1 under these conditions, indicating Happ1-accelerated mHDx-1 clearance does not rely on these processes. In contrast, a calpain inhibitor or an inhibitor of lysosomal pH block Happ1-mediated acceleration of mHDx-1 clearance. These results suggest that mHDx-1 is cleaved by calpain, likely followed by lysosomal degradation and this process regulates the turnover rate of mHDx-1. Sequence analysis identifies amino acid (AA) 15 as a potential calpain cleavage site. Calpain cleavage of recombinant mHDx-1 in vitro yields fragments of sizes corresponding to this prediction. Moreover, when the site is blocked by binding of another intrabody, V_L12.3, turnover of soluble mHDx-1 in living cells is blocked. Conclusions/Significance: These results indicate that calpain-mediated removal of the 15 N-terminal AAs is required for the degradation of mHDx-1, a finding that may have therapeutic implications

Electromagnetic wave diffraction by periodic planar metamaterials with nonlinear constituents

We present a theory which explains how to achieve an enhancement of nonlinear effects in a thin layer of nonlinear medium by involving a planar periodic structure specially designed to bear a trapped-mode resonant regime. In particular, the possibility of a nonlinear thin metamaterial to produce the bistable response at a relatively low input intensity due to a large quality factor of the trapped-mode resonance is shown. Also a simple design of an all-dielectric low-loss silicon-based planar metamaterial which can provide an extremely sharp resonant reflection and transmission is proposed. The designed metamaterial is envisioned for aggregating with a pumped active medium to achieve an enhancement of quantum dots luminescence and to produce an all-dielectric analog of a 'lasing spaser'.Comment: 18 pages, 13 figure

The association of health literacy with adherence in older 2 adults, and its role in interventions: a systematic meta-review

Background: Low health literacy is a common problem among older adults. It is often suggested to be associated with poor adherence. This suggested association implies a need for effective adherence interventions in low health literate people. However, previous reviews show mixed results on the association between low health literacy and poor adherence. A systematic meta-review of systematic reviews was conducted to study the association between health literacy and adherence in adults above the age of 50. Evidence for the effectiveness of adherence interventions among adults in this older age group with low health literacy was also explored. Methods: Eight electronic databases (MEDLINE, ERIC, EMBASE, PsycINFO, CINAHL, DARE, the Cochrane Library, and Web of Knowledge) were searched using a variety of keywords regarding health literacy and adherence. Additionally, references of identified articles were checked. Systematic reviews were included if they assessed the association between health literacy and adherence or evaluated the effectiveness of interventions to improve adherence in adults with low health literacy. The AMSTAR tool was used to assess the quality of the included reviews. The selection procedure, data-extraction, and quality assessment were performed by two independent reviewers. Seventeen reviews were selected for inclusion. Results: Reviews varied widely in quality. Both reviews of high and low quality found only weak or mixed associations between health literacy and adherence among older adults. Reviews report on seven studies that assess the effectiveness of adherence interventions among low health literate older adults. The results suggest that some adherence interventions are effective for this group. The interventions described in the reviews focused mainly on education and on lowering the health literacy demands of adherence instructions. No conclusions could be drawn about which type of intervention could be most beneficial for this population. Conclusions: Evidence on the association between health literacy and adherence in older adults is relatively weak. Adherence interventions are potentially effective for the vulnerable population of older adults with low levels of health literacy, but the evidence on this topic is limited. Further research is needed on the association between health literacy and general health behavior, and on the effectiveness of interventions

Ambient-aware continuous care through semantic context dissemination

Background: The ultimate ambient-intelligent care room contains numerous sensors and devices to monitor the patient, sense and adjust the environment and support the staff. This sensor-based approach results in a large amount of data, which can be processed by current and future applications, e. g., task management and alerting systems. Today, nurses are responsible for coordinating all these applications and supplied information, which reduces the added value and slows down the adoption rate. The aim of the presented research is the design of a pervasive and scalable framework that is able to optimize continuous care processes by intelligently reasoning on the large amount of heterogeneous care data. Methods: The developed Ontology-based Care Platform (OCarePlatform) consists of modular components that perform a specific reasoning task. Consequently, they can easily be replicated and distributed. Complex reasoning is achieved by combining the results of different components. To ensure that the components only receive information, which is of interest to them at that time, they are able to dynamically generate and register filter rules with a Semantic Communication Bus (SCB). This SCB semantically filters all the heterogeneous care data according to the registered rules by using a continuous care ontology. The SCB can be distributed and a cache can be employed to ensure scalability. Results: A prototype implementation is presented consisting of a new-generation nurse call system supported by a localization and a home automation component. The amount of data that is filtered and the performance of the SCB are evaluated by testing the prototype in a living lab. The delay introduced by processing the filter rules is negligible when 10 or fewer rules are registered. Conclusions: The OCarePlatform allows disseminating relevant care data for the different applications and additionally supports composing complex applications from a set of smaller independent components. This way, the platform significantly reduces the amount of information that needs to be processed by the nurses. The delay resulting from processing the filter rules is linear in the amount of rules. Distributed deployment of the SCB and using a cache allows further improvement of these performance results

An in vivo study of the host response to starch-based polymers and composites subcutaneously implanted in rats

Implant failure is one of the major concerns in the biomaterials field. Several factors have been related to the fail but in general these biomaterials do not exhibit comparable physical, chemical or biological properties to natural tissues and ultimately, these devices can lead to chronic inflammation and foreign-body reactions. Starch-based biodegradable materials and composites have shown promising properties for a wide range of biomedical applications as well as a reduced capacity to elicit a strong reaction from immune system cells in vitro. In this work, blends of corn starch with ethylene vinyl alcohol (SEVA-C), cellulose acetate (SCA) and polycaprolactone (SPCL), as well as hydroxyapatite (HA) reinforced starch-based composites, were investigated in vivo. The aim of the work was to assess the host response evoked for starch-based biomaterials, identifying the presence of key cell types. The tissues surrounding the implant were harvested together with the material and processed histologically for evaluation using immunohistochemistry. At implant retrieval there was no cellular exudate around the implants and no macroscopic signs of an inflammatory reaction in any of the animals. The histological analysis of the sectioned interface tissue after immunohistochemical staining using ED1, ED2, CD54, MHC class II and a/b antibodies showed positively stained cells for all antibodies, except for a/b for all the implantation periods, where it was different for the various polymers and for the period of implantation. SPCL and SCA composites were the materials that stimulated the greatest cellular tissue responses, but generally biodegradable starch-based materials did not induce a severe reaction for the studied implantation times, which contrasts with other types of degradable polymeric biomaterials.Fundação para a Ciência e a Tecnologia (FCT

Multi-resolution anisotropy studies of ultrahigh-energy cosmic rays detected at the Pierre Auger Observatory

We report a multi-resolution search for anisotropies in the arrival directions of cosmic rays detected at the Pierre Auger Observatory with local zenith angles up to $80^\circ$ and energies in excess of 4 EeV ($4 \times 10^{18}$ eV). This search is conducted by measuring the angular power spectrum and performing a needlet wavelet analysis in two independent energy ranges. Both analyses are complementary since the angular power spectrum achieves a better performance in identifying large-scale patterns while the needlet wavelet analysis, considering the parameters used in this work, presents a higher efficiency in detecting smaller-scale anisotropies, potentially providing directional information on any observed anisotropies. No deviation from isotropy is observed on any angular scale in the energy range between 4 and 8 EeV. Above 8 EeV, an indication for a dipole moment is captured; while no other deviation from isotropy is observed for moments beyond the dipole one. The corresponding $p$-values obtained after accounting for searches blindly performed at several angular scales, are $1.3 \times 10^{-5}$ in the case of the angular power spectrum, and $2.5 \times 10^{-3}$ in the case of the needlet analysis. While these results are consistent with previous reports making use of the same data set, they provide extensions of the previous works through the thorough scans of the angular scales.Comment: Published version. Added journal reference and DOI. Added Report Numbe