308 research outputs found
Pilot study of the safety and effect of adalimumab on pain, physical function, and musculoskeletal disease in mucopolysaccharidosis types I and II.
Mucopolysaccharidosis I and II are lysosomal storage disorders that, despite treatment with hematopoietic cell transplantation (HCT) and/or enzyme replacement therapy (ERT), continue to cause significant skeletal abnormalities leading to pain, stiffness, physical dysfunction, and short stature. Tumor necrosis factor - alpha (TNF-α) is elevated in individuals with MPS I and II and associated with pain and physical dysfunction. Therefore, we evaluated the safety and effects of the TNF-α inhibitor adalimumab in patients with MPS I and II in a 32-week, randomized, double blind, placebo-controlled, crossover study of adalimumab at a dose of 20 mg (weight 15-<30 kg) or 40 mg (weight ≥ 30 kg) administered subcutaneously every other week or saline placebo for 16 weeks. Participants were evaluated at baseline, week 16, and week 32 with the Children's Health Questionnaire - Parent Form 50 (CHQ-PF50), the Pediatric Pain Questionnaire (PPQ), range-of-motion (ROM) measurements, anthropometry, six-minute walk test (6MWT), hand dynamometer, and laboratory evaluations for safety. The primary outcome was safety and primary efficacy outcome was bodily pain (BP) measured by the CHQ-PF50. Two subjects, one with MPS I and one with MPS II, completed the study. Adalimumab was well tolerated and there were no serious adverse events. Standardized BP scores for age and gender were higher (i.e. less pain) at the end of the treatment versus placebo phase for both subjects. Subject #1 became unblinded during treatment due to skin erythema. Behavior measured by both CHQ-PF50 and parental report improved during treatment compared to placebo in both subjects. ROM improved by > 5° in seven of eight joints in Subject #1 and five of eight joints in Subject #2 (range 7.0° to 52.8°). There was no change in the PPQ, 6MWT, or hand dynamometer. Data from this small pilot study suggest that treatment with adalimumab is safe, tolerable, and may improve ROM, physical function, and possibly pain, in children with MPS I or II. However, additional clinical trials are needed before this therapy should be recommended as part of clinical care
An Alternative Humans to Mars Approach: Reducing Mission Mass with Multiple Mars Flyby Trajectories and Minimal Capability Investments
Mars flyby trajectories and Earth return trajectories have the potential to enable lower- cost and sustainable human exploration of Mars. Flyby and return trajectories are true minimum energy paths with low to zero post-Earth departure maneuvers. By emplacing the large crew vehicles required for human transit on these paths, the total fuel cost can be reduced. The traditional full-up repeating Earth-Mars-Earth cycler concept requires significant infrastructure, but a Mars only flyby approach minimizes mission mass and maximizes opportunities to build-up missions in a stepwise manner. In this paper multiple strategies for sending a crew of 4 to Mars orbit and back are examined. With pre-emplaced assets in Mars orbit, a transit habitat and a minimally functional Mars taxi, a complete Mars mission can be accomplished in 3 SLS launches and 2 Mars Flyby's, including Orion. While some years are better than others, ample opportunities exist within a given 15-year Earth-Mars alignment cycle. Building up a mission cadence over time, this approach can translate to Mars surface access. Risk reduction, which is always a concern for human missions, is mitigated by the use of flybys with Earth return (some of which are true free returns) capability
Social contact and inequalities in depressive symptoms and loneliness among older adults: a mediation analysis of the English Longitudinal Study of Ageing
Background:
Social contact, including remote contact (by telephone, email, letter or text), could help reduce social inequalities in depressive symptoms and loneliness among older adults.
Methods:
Data were from the 8th wave of the English Longitudinal Study of Aging (2016/17), stratified by age (n=1,578 aged <65; n=4,026 aged 65+). Inverse probability weighting was used to estimate average effects of weekly in-person and remote social contact on depressive symptoms (score of 3+ on 8-item CES-D scale) and two measures of loneliness (sometimes/often feels lonely vs hardly ever/never; and top quintile of UCLA loneliness scale vs all others). We also estimated controlled direct effects of education, partner status, and wealth on loneliness and depressive symptoms under two scenarios: 1) universal infrequent (<weekly) in-person social contact; and 2) universal weekly remote social contact.
Results:
Weekly in-person social contact was associated on average with reduced odds of loneliness, but associations with remote social contact were weak. Lower education raised odds of depressive symptoms and loneliness, but differences were attenuated with infrequent in-person contact. Respondents living alone experienced more depressive symptoms and loneliness than those living with a partner, and less wealth was associated with more depressive symptoms. With universal infrequent in-person contact, these differences narrowed among those aged under 65 but widened among those aged 65+. Universal weekly remote contact had relatively little impact on inequalities.
Conclusions:
Reduced in-person social contact may increase depressive symptoms and loneliness among older adults, especially for those aged 65+ who live alone. Reliance on remote social contact seems unlikely to compensate for social inequalities
Pion-nucleus elastic scattering on 12C, 40Ca, 90Zr, and 208Pb at 400 and 500 MeV
Pion-nucleus elastic scattering at energies above the Delta(1232) resonance
is studied using both pi+ and pi- beams on 12C, 40Ca, 90Zr, and 208Pb. The
present data provide an opportunity to study the interaction of pions with
nuclei at energies where second-order corrections to impulse approximation
calculations should be small. The results are compared with other data sets at
similar energies, and with four different first-order impulse approximation
calculations. Significant disagreement exists between the calculations and the
data from this experiment
The sweet spot in sustainability: a framework for corporate assessment in sugar manufacturing
The assessment of corporate sustainability has become an increasingly important topic, both within academia and in industry. For manufacturing companies to conform to their commitments to sustainable development, a standard and reliable measurement framework is required. There is, however, a lack of sector-specific and empirical research in many areas, including the sugar industry. This paper presents an empirically developed framework for the assessment of corporate sustainability within the Thai sugar industry. Multiple case studies were conducted, and a survey using questionnaires was also employed to enhance the power of generalisation. The developed framework is an accurate and reliable measurement instrument of corporate sustainability, and guidelines to assess qualitative criteria are put forward. The proposed framework can be used for a company’s self-assessment and for guiding practitioners in performance improvement and policy decision-maki
Prediction of malignant transformation in oral epithelial dysplasia using infrared absorbance spectra
Oral epithelial dysplasia (OED) is a histopathologically-defined, potentially premalignant condition of the oral cavity. The rate of transformation to frank carcinoma is relatively low (12% within 2 years) and prediction based on histopathological grade is unreliable, leading to both over- and under-treatment. Alternative approaches include infrared (IR) spectroscopy, which is able to classify cancerous and non-cancerous tissue in a number of cancers, including oral. The aim of this study was to explore the capability of FTIR (Fourier-transform IR) microscopy and machine learning as a means of predicting malignant transformation of OED. Supervised, retrospective analysis of longitudinally-collected OED biopsy samples from 17 patients with high risk OED lesions: 10 lesions transformed and 7 did not over a follow-up period of more than 3 years. FTIR spectra were collected from routine, unstained histopathological sections and machine learning used to predict malignant transformation, irrespective of OED classification. PCA-LDA (principal component analysis followed by linear discriminant analysis) provided evidence that the subsequent transforming status of these 17 lesions could be predicted from FTIR data with a sensitivity of 79 ± 5% and a specificity of 76 ± 5%. Six key wavenumbers were identified as most important in this classification. Although this pilot study used a small cohort, the strict inclusion criteria and classification based on known outcome, rather than OED grade, make this a novel study in the field of FTIR in oral cancer and support the clinical potential of this technology in the surveillance of OED
Prediction of malignant transformation in oral epithelial dysplasia using machine learning.
A machine learning algorithm (MLA) has been applied to a Fourier transform infrared spectroscopy (FTIR) dataset previously analysed with a principal component analysis (PCA) linear discriminant analysis (LDA) model. This comparison has confirmed the robustness of FTIR as a prognostic tool for oral epithelial dysplasia (OED). The MLA is able to predict malignancy with a sensitivity of 84 ± 3% and a specificity of 79 ± 3%. It provides key wavenumbers that will be important for the development of devices that can be used for improved prognosis of OED
Equation of state of warm-dense boron nitride combining computation, modeling, and experiment
The equation of state (EOS) of materials at warm dense conditions poses
significant challenges to both theory and experiment. We report a combined
computational, modeling, and experimental investigation leveraging new
theoretical and experimental capabilities to investigate warm-dense boron
nitride (BN). The simulation methodologies include path integral Monte Carlo
(PIMC), several density functional theory (DFT) molecular dynamics methods
[plane-wave pseudopotential, Fermi operator expansion (FOE), and spectral
quadrature (SQ)], activity expansion (ACTEX), and all-electron Green's function
Korringa-Kohn-Rostoker (MECCA), and compute the pressure and internal energy of
BN over a broad range of densities () and temperatures (). Our
experiments were conducted at the Omega laser facility and measured the
Hugoniot of BN to unprecedented pressures (12--30 Mbar). The EOSs computed
using different methods cross validate one another, and the experimental
Hugoniot are in good agreement with our theoretical predictions. We assess that
the largest discrepancies between theoretical predictions are 4% in pressure
and 3% in energy and occur at K. We find remarkable consistency
between the EOS from DFT calculations performed on different platforms and
using different exchange-correlation functionals and those from PIMC using
free-particle nodes. This provides strong evidence for the accuracy of both
PIMC and DFT in the warm-dense regime. Moreover, SQ and FOE data have
significantly smaller error bars than PIMC, and so represent significant
advances for efficient computation at high . We also construct tabular EOS
models and clarify the ionic and electronic structure of BN over a broad
range and quantify their roles in the EOS. The tabular models may be
utilized for future simulations of laser-driven experiments that include BN as
a candidate ablator material.Comment: 19 pages, 14 figures, 4 table
Tissue discrimination in head and neck cancer using image fusion of IR and optical microscopy.
A regression-based fusion algorithm has been used to merge hyperspectral Fourier transform infrared (FTIR) data with an H&E image of oral squamous cell carcinoma metastases in cervical lymphoid nodal tissue. This provides insight into the success of the ratio of FTIR absorbances at 1252 cm-1 and 1285 cm-1 in discriminating between these tissue types. The success is due to absorbances at these two wavenumbers being dominated by contributions from DNA and collagen, respectively. A pixel-by-pixel fit of the fused spectra to the FTIR spectra of collagen, DNA and cytokeratin reveals the contributions of these molecules to the tissue at high spatial resolution
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