Novel MOF-based polymer nanocomposite films were successfully prepared using Zr-based UiO-67 as a metal–organic framework (MOF) and polyurethane (PU) as a polymeric matrix. Synchrotron X-ray powder ...diffraction (SXRPD) analysis confirms the improved stability of the UiO-67 embedded nanocrystals, and scanning electron microscopy images confirm their homogeneous distribution (average crystal size ∼100–200 nm) within the 50 μm thick film. Accessibility to the inner porous structure of the embedded MOFs was completely suppressed for N2 at cryogenic temperatures. However, ethylene adsorption measurements at 25 °C confirm that at least 45% of the MOF crystals are fully accessible for gas-phase adsorption of nonpolar molecules. Although this partial blockage limits the adsorption performance of the embedded MOFs for ocular drugs (e.g., brimonidine tartrate) compared to the pure MOF, an almost 60-fold improvement in the adsorption capacity was observed for the PU matrix after incorporation of the UiO-67 nanocrystals. The UiO-67@PU nanocomposite exhibits a prolonged release of brimonidine (up to 14 days were quantified). Finally, the combined use of SXRPD, thermogravimetric analysis (TGA), and Fourier transform infrared (FTIR) analyses confirmed the presence of the drug in the nanocomposite film, the stability of the MOF framework and the drug upon loading, and the presence of brimonidine in an amorphous phase once adsorbed. These results open the gate toward the application of these polymeric nanocomposite films for drug delivery in ocular therapeutics, either as a component of a contact lens, in the composition of lacrimal stoppers (e.g., punctal plugs), or in subtenon inserts.
We present large-area maps of the CO J = 3-2 emission obtained at the James Clerk Maxwell Telescope for four spiral galaxies in the Virgo Cluster. We combine these data with published CO J = 1-0, 24 ...mm, and Ha images to measure the CO line ratios, molecular gas masses, and instantaneous gas depletion times. For three galaxies in our sample (NGC 4254, NGC 4321, and NGC 4569), we obtain molecular gas masses of 7 X 108 - 3 X 109 M and disk-averaged instantaneous gas depletion times of 1.1-1.7 Gyr. We argue that the CO J = 3-2 line is a better tracer of the dense star-forming molecular gas than the CO J = 1-0 line, as it shows a better correlation with the star formation rate surface density both within and between galaxies. NGC 4254 appears to have a larger star formation efficiency (smaller gas depletion time), perhaps because it is on its first passage through the Virgo Cluster. NGC 4569 shows a large-scale gradient in the gas properties traced by the CO J = 3-2/J = 1-0 line ratio, which suggests that its interaction with the intracluster medium is affecting the dense star-forming portion of the interstellar medium directly. The fourth galaxy in our sample, NGC 4579, has weak CO J = 3-2 emission despite having bright 24 mm emission; however, much of the central luminosity in this galaxy may be due to the presence of a central active galactic nucleus.
Abstract
The James Clerk Maxwell Telescope Nearby Galaxies Legacy Survey (NGLS) comprises an H i-selected sample of 155 galaxies spanning all morphological types with distances less than 25 Mpc. We ...describe the scientific goals of the survey, the sample selection and the observing strategy. We also present an atlas and analysis of the CO J=3 - 2 maps for the 47 galaxies in the NGLS which are also part of the Spitzer Infrared Nearby Galaxies Survey. We find a wide range of molecular gas mass fractions in the galaxies in this sample and explore the correlation of the far-infrared luminosity, which traces star formation, with the CO luminosity, which traces the molecular gas mass. By comparing the NGLS data with merging galaxies at low and high redshift, which have also been observed in the CO J=3 - 2 line, we show that the correlation of far-infrared and CO luminosity shows a significant trend with luminosity. This trend is consistent with a molecular gas depletion time which is more than an order of magnitude faster in the merger galaxies than in nearby normal galaxies. We also find a strong correlation of the L
FIR/L
CO(3-2) ratio with the atomic-to-molecular gas mass ratio. This correlation suggests that some of the far-infrared emission originates from dust associated with atomic gas and that its contribution is particularly important in galaxies where most of the gas is in the atomic phase.
A needs assessment for patients with hidradenitis suppurativa (HS) will support advancements in multidisciplinary care, treatment, research, advocacy, and philanthropy.
To evaluate unmet needs from ...the perspective of HS patients.
Prospective multinational survey of patients between October 2017 and July 2018.
Before receiving a formal HS diagnosis, 63.7% (n = 827) of patients visited a physician ≥5 times. Mean delay in diagnosis was 10.2 ± 8.9 years. Patients experienced flare daily, weekly, or monthly in 23.0%, 29.8%, and 31.1%, respectively. Most (61.4% n = 798) rated recent HS-related pain as moderate or higher, and 4.5% described recent pain to be the worst possible. Access to dermatology was rated as difficult by 37.0% (n = 481). Patients reported visiting the emergency department and hospital ≥5 times for symptoms in 18.3% and 12.5%, respectively. An extreme impact on life was reported by 43.3% (n = 563), and 14.5% were disabled due to disease. Patients reported a high frequency of comorbidities, most commonly mood disorders. Patients were dissatisfied with medical or procedural treatments in 45.9% and 34.6%, respectively.
Data were self-reported. Patients with more severe disease may have been selected.
HS patients have identified several critical unmet needs that will require stakeholder collaboration to meaningfully address.
Abstract Background Treatment options after first-line chemotherapy are limited in non-small cell lung cancer (NSCLC). Belagenpumatucel-L is a therapeutic vaccine comprised of 4 transforming growth ...factor (TGF)-β2-antisense gene-modified, irradiated, allogeneic NSCLC cell lines that may be useful for maintenance after initial treatment. Methods Stage III/IV NSCLC patients who did not progress after platinum-based chemotherapy were randomised 1:1 to receive maintenance belagenpumatucel-L or placebo. Patients were eligible for randomisation between one and four months from the end of induction chemotherapy. The primary endpoint was overall survival. Results This phase III trial enrolled 270 patients in the belagenpumatucel-L arm and 262 in the control arm. Belagenpumatucel-L was well tolerated with no serious safety concerns. There was no difference in survival between the arms (median survival 20.3 versus 17.8 months with belagenpumatucel-L versus placebo, respectively; hazard ratio (HR) 0.94, p = 0.594). There were also no differences in progression-free survival (4.3 months versus 4.0 for belagenpumatucel-L vs placebo, respectively; HR 0.99, p = 0.947). A prespecified Cox regression analysis demonstrated that the time elapsed between randomisation and the end of induction chemotherapy had a significant impact on survival ( p = 0.002) and that prior radiation was a positive prognostic factor (median survival 28.4 months with belagenpumatucel-L versus 16.0 months with placebo; HR 0.61, p = 0.032). Conclusions Although the overall trial did not meet its survival endpoint, improved survival for belagenpumatucel-L is suggested in patients who were randomised within 12 weeks of completion of chemotherapy and in those who had received prior radiation. Further studies of belagenpumatucel-L in NSCLC are warranted.
We used Spitzer Space Telescope 3.6, 8.0, 70 and 160 μm data, James Clerk Maxwell Telescope HARP-B CO J= (3–2) data, National Radio Astronomy Observatory 12 m telescope CO J= (1–0) data and Very ...Large Array H i data to investigate the relations among polycyclic aromatic hydrocarbons (PAHs), cold (∼20 K) dust, molecular gas and atomic gas within NGC 2403, an SABcd galaxy at a distance of 3.13 Mpc. The dust surface density is mainly a function of the total (atomic and molecular) gas surface density and galactocentric radius. The gas-to-dust ratio monotonically increases with radius, varying from ∼100 in the nucleus to ∼400 at 5.5 kpc. The slope of the gas-to-dust ratio is close to that of the oxygen abundance, suggesting that metallicity strongly affects the gas-to-dust ratio within this galaxy. The exponential scale length of the radial profile for the CO J= (3–2) emission is statistically identical to the scale length for the stellar continuum-subtracted 8 μm (PAH 8 μm) emission. However, CO J= (3–2) and PAH 8 μm surface brightnesses appear uncorrelated when examining sub-kpc-sized regions.
Background
Hidradenitis suppurativa (HS) is a painful chronic, recurrent inflammatory skin disease with great impact on health‐related quality of life (HRQOL). Recently, Hidradenitis SuppuraTiva cORe ...outcomes set International Collaboration (HISTORIC) established HRQOL as a core domain set for HS clinical trials and developed the Hidradenitis Suppurativa Quality of Life (HiSQOL) as a validated outcome measurement instrument.
Objectives
To provide further convergent validity of HiSQOL by comparing it to Dermatology Life Quality Index (DLQI) and Pictorial Representation of Illness and Self Measure‐Revised 2 (PRISM‐R2).
Methods
In this cross‐sectional study, 103 participants completed HiSQOL, PRISM‐R2 and DLQI. PRISM‐R2 is an instrument designed to measure suffering and reports the two measures, Illness Perception Measure (IPM) and Self‐Illness Separation (SIS). Correlation analyses were performed including a sub‐analysis for a subgroup of patients with high scores in the HS‐specific domains of HiSQOL.
Results
A very strong correlation was found between HiSQOL and DLQI (ρ = 0.93, P < 2.2 × 10−16, (95% CI: 0.89;0.95)), and moderately strong correlations were found between HiSQOL and SIS (ρ = −0.73, P < 2.2 × 10−16, (95% CI: −0.81; −0.62)) and DLQI and SIS (ρ = −0.70, P < 2.2 × 10−16, (95% CI: −0.79; −0.59)). IPM was positively associated with HiSQOL and DLQI and negatively with SIS.
Conclusions
HiSQOL is a valid measure of quality of life for HS patients, and we suggest that HiSQOL can be used as a measure of suffering as well.
Linked commentary: C.C. Zoubouli et al. J Eur Acad Dermatol Venereol 2021; 35: 1420–1421. https://doi.org/10.1111/jdv.17306.
In a literature survey, Chernoff et al. (
2017
) dismissed the hypothesis that chronic exposure to β-
N
-methylamino-L-alanine (BMAA) may be a risk factor for progressive neurodegenerative disease. ...They question the growing scientific literature that suggests the following: (1) BMAA exposure causes ALS/PDC among the indigenous Chamorro people of Guam; (2) Guamanian ALS/PDC shares clinical and neuropathological features with Alzheimer’s disease, Parkinson’s disease, and ALS; (3) one possible mechanism for protein misfolds is misincorporation of BMAA into proteins as a substitute for L-serine; and (4) chronic exposure to BMAA through diet or environmental exposures to cyanobacterial blooms can cause neurodegenerative disease. We here identify multiple errors in their critique including the following: (1) their review selectively cites the published literature; (2) the authors reported favorably on HILIC methods of BMAA detection while the literature shows significant matrix effects and peak coelution in HILIC that may prevent detection and quantification of BMAA in cyanobacteria; (3) the authors build alternative arguments to the BMAA hypothesis, rather than explain the published literature which, to date, has been unable to refute the BMAA hypothesis; and (4) the authors erroneously attribute methods to incorrect studies, indicative of a failure to carefully consider all relevant publications. The lack of attention to BMAA research begins with the review’s title which incorrectly refers to BMAA as a “non-essential” amino acid. Research regarding chronic exposure to BMAA as a cause of human neurodegenerative diseases is emerging and requires additional resources, validation, and research. Here, we propose strategies for improvement in the execution and reporting of analytical methods and the need for additional and well-executed inter-lab comparisons for BMAA quantitation. We emphasize the need for optimization and validation of analytical methods to ensure that they are fit-for-purpose. Although there remain gaps in the literature, an increasingly large body of data from multiple independent labs using orthogonal methods provides increasing evidence that chronic exposure to BMAA may be a risk factor for neurological illness.
Background
Hidradenitis suppurativa (HS) is a chronic inflammatory disease. The HS core outcome set calls for a patient global assessment (PtGA).
Objectives
To assess the validity, reliability and ...responsiveness of a candidate single‐item PtGA for HS‐specific health‐related quality of life (HRQoL).
Methods
Cognitive debriefing interviews were conducted with patients with HS in Denmark and the USA. A cross‐sectional observational study was done with adults with HS in the USA and Denmark. Candidate PtGA item, demographic items and multiple patient‐reported scales – the Hidradenitis Suppurativa Quality of Life (HiSQOL), Dermatology Life Quality Index (DLQI) and numerical rating scale (NRS) for pain – were concurrently administered to evaluate convergent and known‐groups validity. Scales with a single‐item assessment of change were readministered 24–72 h later, to evaluate reliability and responsiveness.
Results
After cognitive debriefing, the candidate PtGA for HS‐specific HRQoL was finalized with five response levels. Convergent validity of the PtGA was supported by significant correlations with HiSQOL score r = 0·79, 95% confidence interval (CI) 0·75–0·82 and DLQI (r = 0·78, 95% CI 0·74–0·82). The PtGA displayed known‐groups validity with DLQI score bands based on significance of an anova (P < 0·001). Good test–retest reliability was supported by the intraclass correlation coefficient (0·82, 95% CI 0·78–0·85) for those who reported stable HS. Responsiveness was assessed by differences in PtGA score against a patient‐reported assessment of change, which showed significant differences towards improvement.
Conclusions
The single‐item PtGA exhibits reliability, validity and responsiveness in assessing HS‐specific HRQoL in HS, making it a good provisional tool for HS clinical research.
What is already known about this topic?
Hidradenitis suppurativa (HS) can have a large negative impact on health‐related quality of life (HRQoL).
Patient global assessments are useful in eliciting important aspects of the patient’s perspective on an individual basis.
Few studies have developed and investigated the measurement properties of a patient global assessment (PtGA) item for HS.
What does this study add?
This study describes the development, validation and psychometric properties of a PtGA item for HS.
This PtGA item for HRQoL shows promise with its validity and reliability, allowing for its further development as a clinical research tool.
What are the clinical implications of this work?
The PtGA item can now be investigated longitudinally in a treated population to further elucidate the responsiveness, minimally important change and score bands.
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