Scent-delivery devices as a digital healthcare tool for olfactory training: A pilot focus group study in Parkinson's disease patients

Parkinson's disease (PD) patients display a combination of motor and non-motor symptoms. The most common non-motor symptom is scent (olfactory) impairment, occurring at least four years prior to motor symptom onset. Recent and growing interest in digital healthcare technology used in PD has resulted in more technologies developed for motor rather than non-motor symptoms. Human-computer interaction (HCI), which uses computer technology to explore human activity and work, could be combined with digital healthcare technologies to better understand and support olfaction via scent training - leading to the development of a scent-delivery device (SDD). In this pilot study, three PD patients were invited to an online focus group to explore the association between PD and olfaction, understand HCI and sensory technologies and were demonstrated a new multichannel SDD with an associated mobile app. Participants had a preconceived link, a result of personal experience, between olfactory impairment and PD. Participants felt that healthcare professionals did not take olfactory dysfunction concerns seriously prior to PD diagnosis. Two were not comfortable with sharing scent loss experiences with others. Participants expected the multichannel SDD to be small, portable and easy-to-use, with customisable cartridges to deliver chosen scents and the mobile app to create a sense of community. None of the participants regularly performed scent training but would consider doing so if some scent function could be regained. Standardised digital SDDs for regular healthcare check-ups may facilitate improvement in olfactory senses in PD patients and potential earlier PD diagnosis, allowing earlier therapeutic and symptomatic PD management

Covariance Assisted Multivariate Penalized Additive Regression (CoMPAdRe)

We propose a new method for the simultaneous selection and estimation of multivariate sparse additive models with correlated errors. Our method called Covariance Assisted Multivariate Penalized Additive Regression (CoMPAdRe) simultaneously selects among null, linear, and smooth non-linear effects for each predictor while incorporating joint estimation of the sparse residual structure among responses, with the motivation that accounting for inter-response correlation structure can lead to improved accuracy in variable selection and estimation efficiency. CoMPAdRe is constructed in a computationally efficient way that allows the selection and estimation of linear and non-linear covariates to be conducted in parallel across responses. Compared to single-response approaches that marginally select linear and non-linear covariate effects, we demonstrate in simulation studies that the joint multivariate modeling leads to gains in both estimation efficiency and selection accuracy, of greater magnitude in settings where signal is moderate relative to the level of noise. We apply our approach to protein-mRNA expression levels from multiple breast cancer pathways obtained from The Cancer Proteome Atlas and characterize both mRNA-protein associations and protein-protein subnetworks for each pathway. We find non-linear mRNA-protein associations for the Core Reactive, EMT, PIK-AKT, and RTK pathways

A Cross-sectional study on Out-of-Pocket expenditure towards Immunization and its consequences faced by families with under-five Children Residing at one of the Cities of Western India

Background: When immunization of under-five children results in Out-of-Pocket Expenditure (OOPE), it affects motivation of parents for vaccination inversely. Objectives: To assess determinants affecting preference for specific/mixed type of health facilities and to estimate out-of-pocket expenditure towards immunization of under-five children. To assess opinion of participants for prevention/decreasing OOPE towards immunization. Methods: A community-based cross-sectional study was conducted at one of zones of Ahmedabad city, selected by simple random sampling. Following technique of “30×7 cluster survey” with necessary house-hold information received from Municipal Corporation, selection of 7 children was pursued from each cluster reaching to sample-size of 210 (30 X 7). Results: Of 211 children included in study, 124(58.77%), 68(32.23%) and 19(9%) had taken immunization services from government, private and mixed variety respectively. Majority of families (110, 88.71%) preferring government healthcare-facility for immunization incurred expenses <5000 INR/child as while in other two groups, all beneficiaries had expensed>5000 INR/child. Conclusions: Determinants like child’s gender, parents’ education, Type of family, Socio-economic status, delivery place of child and occupation of father had statistically significant association with preferred place of vaccination. Fixation of upper ceiling-limit of vaccines which are recommended by pediatricians but not covered in government run program was one of suggestions

Modernising Orodispersible Film Characterisation to Improve Palatability and Acceptability Using a Toolbox of Techniques

Orodispersible films (ODFs) have been widely used in paediatric, geriatric and dysphagic patients due to ease of administration and precise and flexible dose adjustments. ODF fabrication has seen significant advancements with the move towards more technologically advanced production methods. The acceptability of ODFs is dependent upon film composition and process of formation, which affects disintegration, taste, texture and mouthfeel. There is currently a lack of testing to accurately assess ODFs for these important acceptability sensory perceptions. This study produced four ODFs formed of polyvinyl alcohol and sodium carboxymethylcellulose using 3D printing. These were assessed using three in vitro methods: Petri dish and oral cavity model (OCM) methods for disintegration and bio-tribology for disintegration and oral perception. Increasing polymer molecular weight (MW) exponentially increased disintegration time in the Petri dish and OCM methods. Higher MW films adhered to the OCM upper palate. Bio-tribology analysis showed that films of higher MW disintegrated quickest and had lower coefficient of friction, perhaps demonstrating good oral perception but also stickiness, with higher viscosity. These techniques, part of a toolbox, may enable formulators to design, test and reformulate ODFs that both disintegrate rapidly and may be better perceived when consumed, improving overall treatment acceptability

Comprehensive quantification of height dependence of entrainment mixing between stratiform cloud top and environment

Different entrainment-mixing processes of turbulence are crucial to processes related to clouds; however, only a few qualitative studies have been concentrated on the vertical distributions of entrainment-mixing mechanisms with low vertical resolutions. To quantitatively study vertical profiles of entrainment-mixing mechanisms with a high resolution, the stratiform clouds observed in the Physics of Stratocumulus Top (POST) project are examined. The unique sawtooth flight pattern allows for an examination of the vertical distributions of entrainment-mixing mechanisms with a 5ĝ€¯m vertical resolution. Relative standard deviation of volume mean radius divided by relative standard deviation of liquid water content is introduced to be a new estimation of microphysical homogeneous mixing degree, to overcome difficulties of determining the adiabatic microphysical properties required in existing measures. The vertical profile of this new measure indicates that entrainment-mixing mechanisms become more homogeneous with decreasing altitudes and are consistent with the dynamical measures of Damköhler number and transition scale number. Further analysis shows that the vertical variation of entrainment-mixing mechanisms with decreasing altitudes is due to the increases of turbulent dissipation rate in cloud and relative humidity in droplet-free air and the decrease of size of droplet-free air. The results offer insights into the theoretical understanding and parameterizations of vertical variation of entrainment-mixing mechanisms

Noise analysis of the Indian Pulsar Timing Array data release I

The Indian Pulsar Timing Array (InPTA) collaboration has recently made its first official data release (DR1) for a sample of 14 pulsars using 3.5 years of uGMRT observations. We present the results of single-pulsar noise analysis for each of these 14 pulsars using the InPTA DR1. For this purpose, we consider white noise, achromatic red noise, dispersion measure (DM) variations, and scattering variations in our analysis. We apply Bayesian model selection to obtain the preferred noise models among these for each pulsar. For PSR J1600−3053, we find no evidence of DM and scattering variations, while for PSR J1909−3744, we find no significant scattering variations. Properties vary dramatically among pulsars. For example, we find a strong chromatic noise with chromatic index ∼ 2.9 for PSR J1939+2134, indicating the possibility of a scattering index that doesn’t agree with that expected for a Kolmogorov scattering medium consistent with similar results for millisecond pulsars in past studies. Despite the relatively short time baseline, the noise models broadly agree with the other PTAs and provide, at the same time, well-constrained DM and scattering variations

In Vivo Targeting through Click Chemistry

Targeting small molecules to diseased tissues as therapy or diagnosis is a significant challenge in drug delivery. Drug-eluting devices implanted during invasive surgery allow the controlled presentation of drugs at the disease site, but cannot be modified once the surgery is complete. We demonstrate that bioorthogonal click chemistry can be used to target circulating small molecules to hydrogels resident intramuscularly in diseased tissues. We also demonstrate that small molecules can be repeatedly targeted to the diseased area over the course of at least one month. Finally, two bioorthogonal reactions were used to segregate two small molecules injected as a mixture to two separate locations in a mouse disease model. These results demonstrate that click chemistry can be used for pharmacological drug delivery, and this concept is expected to have applications in refilling drug depots in cancer therapy, wound healing, and drug-eluting vascular grafts and stents.Engineering and Applied Science

Gender Differences in Presentation, Management, and In-Hospital Outcomes for Patients with AMI in a Lower-Middle Income Country: Evidence from Egypt

BACKGROUND: Many studies in high-income countries have investigated gender differences in the care and outcomes of patients hospitalized with acute myocardial infarction (AMI). However, little evidence exists on gender differences among patients with AMI in lower-middle-income countries, where the proportion deaths stemming from cardiovascular disease is projected to increase dramatically. This study examines gender differences in patients in the lower-middle-income country of Egypt to determine if female patients with AMI have a different presentation, management, or outcome compared with men. METHODS AND FINDINGS: Using registry data collected over 18 months from 5 Egyptian hospitals, we considered 1204 patients (253 females, 951 males) with a confirmed diagnosis of AMI. We examined gender differences in initial presentation, clinical management, and in-hospital outcomes using t-tests and χ(2) tests. Additionally, we explored gender differences in in-hospital death using multivariate logistic regression to adjust for age and other differences in initial presentation. We found that women were older than men, had higher BMI, and were more likely to have hypertension, diabetes mellitus, dyslipidemia, heart failure, and atrial fibrillation. Women were less likely to receive aspirin upon admission (p<0.01) or aspirin or statins at discharge (p = 0.001 and p<0.05, respectively), although the magnitude of these differences was small. While unadjusted in-hospital mortality was significantly higher for women (OR: 2.10; 95% CI: 1.54 to 2.87), this difference did not persist in the fully adjusted model (OR: 1.18; 95% CI: 0.55 to 2.55). CONCLUSIONS: We found that female patients had a different profile than men at the time of presentation. Clinical management of men and women with AMI was similar, though there are small but significant differences in some areas. These gender differences did not translate into differences in in-hospital outcome, but highlight differences in quality of care and represent important opportunities for improvement

Noise analysis of the Indian Pulsar Timing Array data release I

The Indian Pulsar Timing Array (InPTA) collaboration has recently made its first official data release (DR1) for a sample of 14 pulsars using 3.5 years of uGMRT observations. We present the results of single-pulsar noise analysis for each of these 14 pulsars using the InPTA DR1. For this purpose, we consider white noise, achromatic red noise, dispersion measure (DM) variations, and scattering variations in our analysis. We apply Bayesian model selection to obtain the preferred noise models among these for each pulsar. For PSR J1600$-$3053, we find no evidence of DM and scattering variations, while for PSR J1909$-$3744, we find no significant scattering variations. Properties vary dramatically among pulsars. For example, we find a strong chromatic noise with chromatic index $\sim$ 2.9 for PSR J1939+2134, indicating the possibility of a scattering index that doesn't agree with that expected for a Kolmogorov scattering medium consistent with similar results for millisecond pulsars in past studies. Despite the relatively short time baseline, the noise models broadly agree with the other PTAs and provide, at the same time, well-constrained DM and scattering variations.Comment: Accepted for publication in PRD, 30 pages, 17 figures, 4 table

Multi-band Extension of the Wideband Timing Technique

The wideband timing technique enables the high-precision simultaneous estimation of Times of Arrival (ToAs) and Dispersion Measures (DMs) while effectively modeling frequency-dependent profile evolution. We present two novel independent methods that extend the standard wideband technique to handle simultaneous multi-band pulsar data incorporating profile evolution over a larger frequency span to estimate DMs and ToAs with enhanced precision. We implement the wideband likelihood using the libstempo python interface to perform wideband timing in the tempo2 framework. We present the application of these techniques to the dataset of fourteen millisecond pulsars observed simultaneously in Band 3 (300 - 500 MHz) and Band 5 (1260 - 1460 MHz) of the upgraded Giant Metrewave Radio Telescope (uGMRT) as a part of the Indian Pulsar Timing Array (InPTA) campaign. We achieve increased ToA and DM precision and sub-microsecond root mean square post-fit timing residuals by combining simultaneous multi-band pulsar observations done in non-contiguous bands for the first time using our novel techniques.Comment: Submitted to MNRA