Process Monitoring of Moisture Content and Mass Transfer Rate in a Fluidised Bed with a Low Cost Inline MEMS NIR Sensor

Purpose The current trend for continuous drug product manufacturing requires new, affordable process analytical techniques (PAT) to ensure control of processing. This work evaluates whether property models based on spectral data from recent Fabry–Pérot Interferometer based NIR sensors can generate a high-resolution moisture signal suitable for process control. Methods Spectral data and offline moisture content were recorded for 14 fluid bed dryer batches of pharmaceutical granules. A PLS moisture model was constructed resulting in a high resolution moisture signal, used to demonstrate (i) endpoint determination and (ii) evaluation of mass transfer performance. Results The sensors appear robust with respect to vibration and ambient temperature changes, and the accuracy of water content predictions (±13 % ) is similar to those reported for high specification NIR sensors. Fusion of temperature and moisture content signal allowed monitoring of water transport rates in the fluidised bed and highlighted the importance water transport within the solid phase at low moisture levels. The NIR data was also successfully used with PCA-based MSPC models for endpoint detection. Conclusions The spectral quality of the small form factor NIR sensor and its robustness is clearly sufficient for the construction and application of PLS models as well as PCA-based MSPC moisture models. The resulting high resolution moisture content signal was successfully used for endpoint detection and monitoring the mass transfer rate

Odderon in baryon-baryon scattering from the AdS/CFT correspondence

Based on the AdS/CFT correspondence, we present a holographic description of various C-odd exchanges in high energy baryon-baryon and baryon-antibaryon scattering, and calculate their respective contributions to the difference in the total cross sections. We predict that, due to the warp factor of AdS_5, the total cross section in pp collisions is larger than in p\bar{p} collisions at asymptotically high energies.Comment: 23 pages, v2: minor changes, to be published in JHE

Calcium Homeostasis in Myogenic Differentiation Factor 1 (MyoD)-Transformed, Virally-Transduced, Skin-Derived Equine Myotubes

Dysfunctional skeletal muscle calcium homeostasis plays a central role in the pathophysiology of several human and animal skeletal muscle disorders, in particular, genetic disorders associated with ryanodine receptor 1 (RYR1) mutations, such as malignant hyperthermia, central core disease, multiminicore disease and certain centronuclear myopathies. In addition, aberrant skeletal muscle calcium handling is believed to play a pivotal role in the highly prevalent disorder of Thoroughbred racehorses, known as Recurrent Exertional Rhabdomyolysis. Traditionally, such defects were studied in human and equine subjects by examining the contractile responses of biopsied muscle strips exposed to caffeine, a potent RYR1 agonist. However, this test is not widely available and, due to its invasive nature, is potentially less suitable for valuable animals in training or in the human paediatric setting. Furthermore, increasingly, RYR1 gene polymorphisms (of unknown pathogenicity and significance) are being identified through next generation sequencing projects. Consequently, we have investigated a less invasive test that can be used to study calcium homeostasis in cultured, skin-derived fibroblasts that are converted to the muscle lineage by viral transduction with a MyoD (myogenic differentiation 1) transgene. Similar models have been utilised to examine calcium homeostasis in human patient cells, however, to date, there has been no detailed assessment of the cells’ calcium homeostasis, and in particular, the responses to agonists and antagonists of RYR1. Here we describe experiments conducted to assess calcium handling of the cells and examine responses to treatment with dantrolene, a drug commonly used for prophylaxis of recurrent exertional rhabdomyolysis in horses and malignant hyperthermia in humans

Peripheral nervous system manifestations in a Sandhoff disease mouse model: nerve conduction, myelin structure, lipid analysis

<p>Abstract</p> <p>Background</p> <p>Sandhoff disease is an inherited lysosomal storage disease caused by a mutation in the gene for the β-subunit (<it>Hexb </it>gene) of β-hexosaminidase A (αβ) and B (ββ). The β-subunit together with the GM2 activator protein catabolize ganglioside GM2. This enzyme deficiency results in GM2 accumulation primarily in the central nervous system. To investigate how abnormal GM2 catabolism affects the peripheral nervous system in a mouse model of Sandhoff disease (<it>Hexb-/-</it>), we examined the electrophysiology of dissected sciatic nerves, structure of central and peripheral myelin, and lipid composition of the peripheral nervous system.</p> <p>Results</p> <p>We detected no significant difference in signal impulse conduction velocity or any consistent change in the frequency-dependent conduction slowing and failure between freshly dissected sciatic nerves from the <it>Hexb</it>+/- and <it>Hexb</it>-/- mice. The low-angle x-ray diffraction patterns from freshly dissected sciatic and optic nerves of <it>Hexb</it>+/- and <it>Hexb</it>-/- mice showed normal myelin periods; however, <it>Hexb</it>-/- mice displayed a ~10% decrease in the relative amount of compact optic nerve myelin, which is consistent with the previously established reduction in myelin-enriched lipids (cerebrosides and sulfatides) in brains of <it>Hexb-/- </it>mice. Finally, analysis of lipid composition revealed that GM2 content was present in the sciatic nerve of the <it>Hexb</it>-/- mice (undetectable in <it>Hexb</it>+/-).</p> <p>Conclusion</p> <p>Our findings demonstrate the absence of significant functional, structural, or compositional abnormalities in the peripheral nervous system of the murine model for Sandhoff disease, but do show the potential value of integrating multiple techniques to evaluate myelin structure and function in nervous system disorders.</p

Phenotypic redshifts with self-organizing maps: A novel method to characterize redshift distributions of source galaxies for weak lensing

Wide-field imaging surveys such as the Dark Energy Survey (DES) rely on coarse measurements of spectral energy distributions in a few filters to estimate the redshift distribution of source galaxies. In this regime, sample variance, shot noise, and selection effects limit the attainable accuracy of redshift calibration and thus of cosmological constraints. We present a new method to combine wide-field, few-filter measurements with catalogs from deep fields with additional filters and sufficiently low photometric noise to break degeneracies in photometric redshifts. The multi-band deep field is used as an intermediary between wide-field observations and accurate redshifts, greatly reducing sample variance, shot noise, and selection effects. Our implementation of the method uses self-organizing maps to group galaxies into phenotypes based on their observed fluxes, and is tested using a mock DES catalog created from N-body simulations. It yields a typical uncertainty on the mean redshift in each of five tomographic bins for an idealized simulation of the DES Year 3 weak-lensing tomographic analysis of $\sigma_{\Delta z} = 0.007$, which is a 60% improvement compared to the Year 1 analysis. Although the implementation of the method is tailored to DES, its formalism can be applied to other large photometric surveys with a similar observing strategy.Comment: 24 pages, 11 figures; matches version accepted to MNRA

Testing the isotropy of the dark energy Survey's extreme trans-neptunian objects

We test whether the population of "extreme"trans-Neptunian objects (eTNOs) detected in the first four years of the Dark Energy Survey (DES Y4) data exhibit azimuthal asymmetries that might be evidence of gravitational perturbations from an unseen super-Earth in a distant orbit. By rotating the orbits of the detected eTNOs, we construct a synthetic population that, when subject to the DES selection function, reproduces the detected distribution of eTNOs in the orbital elements a, e, and i as well as absolute magnitude H, but has uniform distributions in mean anomaly M, longitude of ascending node Ω, and argument of perihelion ω. We then compare the detected distributions in each of Ω, ω, and the longitude of perihelion {equation presented} to those expected from the isotropic population, using Kuiper's variant of the Kolmogorov-Smirnov test. The three angles are tested for each of four definitions of the eTNO population, choosing among a > (150, 250) au and perihelion q > (30, 37) au. These choices yield 3-7 eTNOs in the DES Y4 sample. Among the 12 total tests, two have the likelihood of drawing the observed angles from the isotropic population at p 250 and q > 37 au and the four detections at a > 250 and q > 30 au have a Ω distribution with p ≈ 0.03 coming from the isotropic construction, but this is not strong evidence of anisotropy given the 12 different tests. The DES data taken on their own are thus consistent with azimuthal isotropy and do not require a "Planet 9"hypothesis. The limited sky coverage and object count mean, however, that the DES data by no means falsify this hypothesis

Testing the isotropy of the Dark Energy Survey's extreme trans-Neptunian objects

We test whether the population of "extreme" trans-Neptunian objects (eTNOs) detected in the Y4 Dark Energy Survey (DES) data exhibit azimuthal asymmetries which might be evidence of gravitational perturbations from an unseen super-Earth in a distant orbit. By rotating the orbits of the detected eTNOs, we construct a synthetic population which, when subject to the DES selection function, reproduces the detected distribution of eTNOs in the orbital elements $a,e,$ and $i$ as well as absolute magnitude $H$, but has uniform distributions in mean anomaly $M$, longitude of ascending node $\Omega,$ and argument of perihelion $\omega.$ We then compare the detected distributions in each of $\Omega, \omega,$ and $\varpi\equiv\Omega+\omega$ to those expected from the isotropic population, using Kuiper's variant of the Kolmogorov-Smirnov test. The three angles are tested for each of 4 definitions of the eTNO population, choosing among $a>(150,250)$ AU and perihelion $q>(30,37)$ AU. These choices yield 3--7 eTNOs in the DES Y4 sample. Among the twelve total tests, two have the likelihood of drawing the observed angles from the isotropic population at $p250, q>37$ AU, and the 4 detections at $a>250, q>30$ AU, have $\Omega$ distribution with $p=0.03$ of coming from the isotropic construction, but this is not strong evidence of anisotropy given the 12 different tests. The DES data taken on their own are thus consistent with azimuthal isotropy and do not require a "Planet 9" hypothesis. The limited sky coverage and object count mean, however, that the DES data by no means falsify this hypothesis.Comment: Accepted on PS

Computerized ICU Data Management Pitfalls and Promises

journal articleBiomedical Informatic

The Conceptual Definition of Sarcopenia: Delphi Consensus from the Global Leadership Initiative in Sarcopenia (GLIS)

\ua9 2024 The Author(s).Importance: Sarcopenia, the age-related loss of muscle mass and strength/function, is an important clinical condition. However, no international consensus on the definition exists. Objective: The Global Leadership Initiative in Sarcopenia (GLIS) aimed to address this by establishing the global conceptual definition of sarcopenia. Design: The GLIS steering committee was formed in 2019-21 with representatives from all relevant scientific societies worldwide. During this time, the steering committee developed a set of statements on the topic and invited members from these societies to participate in a two-phase International Delphi Study. Between 2022 and 2023, participants ranked their agreement with a set of statements using an online survey tool (SurveyMonkey). Statements were categorised based on predefined thresholds: strong agreement (&gt;80%), moderate agreement (70-80%) and low agreement (&lt;70%). Statements with strong agreement were accepted, statements with low agreement were rejected and those with moderate agreement were reintroduced until consensus was reached. Results: 107 participants (mean age: 54 \ub1 12 years [1 missing age], 64% men) from 29 countries across 7 continents/regions completed the Delphi survey. Twenty statements were found to have a strong agreement. These included; 6 statements on \u27general aspects of sarcopenia\u27 (strongest agreement: the prevalence of sarcopenia increases with age (98.3%)), 3 statements on \u27components of sarcopenia\u27 (muscle mass (89.4%), muscle strength (93.1%) and muscle-specific strength (80.8%) should all be a part of the conceptual definition of sarcopenia)) and 11 statements on \u27outcomes of sarcopenia\u27 (strongest agreement: sarcopenia increases the risk of impaired physical performance (97.9%)). A key finding of the Delphi survey was that muscle mass, muscle strength and muscle-specific strength were all accepted as \u27components of sarcopenia\u27, whereas impaired physical performance was accepted as an \u27outcome\u27 rather than a \u27component\u27 of sarcopenia. Conclusion and relevance: The GLIS has created the first global conceptual definition of sarcopenia, which will now serve to develop an operational definition for clinical and research settings