The Engagement Pathway: A Conceptual Framework of Engagement-Related Terms in Weight Management

Engagement denotes the extent to which, and how, individuals participate in weight management (WM) services. Effective WM services should generate meaningful outcomes and promote high participant engagement; however, research is predominantly focused on the former. Given that engagement is a poorly understood phenomenon, and that engagement-related concepts are often used synonymously (e.g., dropout and attrition), the engagement pathway is hereby introduced. This pathway defines key concepts (e.g., recruitment, adherence, attrition) and their relationships in the enrolment, intervention, and maintenance stages of treatment. The pathway will help researchers and practitioners better understand engagement-related concepts whilst encouraging greater conceptual consistency between studies

Can shoulder range of movement be measured accurately using the Microsoft Kinect sensor plus Medical Interactive Recovery Assistant (MIRA) software?

BackgroundThis study compared the accuracy of measuring shoulder range of movement (ROM) with a simple laptop-sensor combination vs. trained observers (shoulder physiotherapists and shoulder surgeons) using motion capture (MoCap) laboratory equipment as the gold standard. MethodsThe Microsoft Kinect sensor (Microsoft Corp., Redmond, WA, USA) tracks 3-dimensional human motion. Ordinarily used with an Xbox (Microsoft Corp.) video game console, Medical Interactive Recovery Assistant (MIRA) software (MIRA Rehab Ltd., London, UK) allows this small sensor to measure shoulder movement with a standard computer. Shoulder movements of 49 healthy volunteers were simultaneously measured by trained observers, MoCap, and the MIRA device. Internal rotation was assessed with the shoulder abducted 90° and external rotation with the shoulder adducted. Visual estimation and MIRA measurements were compared with gold standard MoCap measurements for agreement using Bland-Altman methods. Results There were 1670 measurements analyzed. The MIRA evaluations of all 4 cardinal shoulder movements were significantly more precise, with narrower limits of agreement, than the measurements of trained observers. MIRA achieved ±11° (95% confidence interval [CI], 8.7°-12.6°) for forward flexion vs. ±16° (95% CI, 14.6°-17.6°) by trained observers. For abduction, MIRA showed ±11° (95% CI, 8.7°-12.8°) against ±15° (95% CI, 13.4°-16.2°) for trained observers. MIRA attained ±10° (95% CI, 8.1°-11.9°) during external rotation measurement, whereas trained observers only reached ±21° (95% CI, 18.7°-22.6°). For internal rotation, MIRA achieved ±9° (95% CI, 7.2°-10.4°), which was again better than TOs at ±18° (95% CI, 16.0°-19.3°). ConclusionsA laptop combined with a Microsoft Kinect sensor and the MIRA software can measure shoulder movements with acceptable levels of accuracy. This technology, which can be easily set up, may also allow precise shoulder ROM measurement outside the clinic setting

The global dynamics of RNA stability orchestrates responses to cellular activation

Transcriptomics is used to quantify changes in accumulated levels of mRNAs following cellular activation. These changes arise from the opposing fluxes of transcription and mRNA decay, both of which affect the functional dynamics of global gene expression. A study published recently in BMC Genomics focuses on the contribution made by mRNA stability in shaping the kinetics of gene responses in mammalian cells

Fluoxetine: a case history of its discovery and preclinical development

Introduction: Depression is a multifactorial mood disorder with a high prevalence worldwide. Until now, treatments for depression have focused on the inhibition of monoaminergic reuptake sites, which augment the bioavailability of monoamines in the CNS. Advances in drug discovery have widened the therapeutic options with the synthesis of so-called selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine. Areas covered: The aim of this case history is to describe and discuss the pharmacokinetic and pharmacodynamic profiles of fluoxetine, including its acute effects and the adaptive changes induced after long-term treatment. Furthermore, the authors review the effect of fluoxetine on neuroplasticity and adult neurogenesis. In addition, the article summarises the preclinical behavioural data available on fluoxetine’s effects on depressive-like behaviour, anxiety and cognition as well as its effects on other diseases. Finally, the article describes the seminal studies validating the antidepressant effects of fluoxetine. Expert opinion: Fluoxetine is the first selective SSRI that has a recognised clinical efficacy and safety profile. Since its discovery, other molecules that mimic its mechanism of action have been developed, commencing a new age in the treatment of depression. Fluoxetine has also demonstrated utility in the treatment of other disorders for which its prescription has now been approved

Alginate inhibits iron absorption from ferrous gluconate in a randomized controlled trial and reduces iron uptake into Caco-2 cells

Previous in vitro results indicated that alginate beads might be a useful vehicle for food iron fortification. A human study was undertaken to test the hypothesis that alginate enhances iron absorption. A randomised, single blinded, cross-over trial was carried out in which iron absorption was measured from serum iron appearance after a test meal. Overnight-fasted volunteers (n=15) were given a test meal of 200g cola-flavoured jelly plus 21 mg iron as ferrous gluconate, either in alginate beads mixed into the jelly or in a capsule. Iron absorption was lower from the alginate beads than from ferrous gluconate (8.5% and 12.6% respectively, p=0.003). Sub-group B (n=9) consumed the test meals together with 600 mg calcium to determine whether alginate modified the inhibitory effect of calcium. Calcium reduced iron absorption from ferrous gluconate by 51%, from 11.5% to 5.6% (p=0.014), and from alginate beads by 37%, from 8.3% to 5.2% (p=0.009). In vitro studies using Caco-2 cells were designed to explore the reasons for the difference between the previous in vitro findings and the human study; confirmed the inhibitory effect of alginate. Beads similar to those used in the human study were subjected to simulated gastrointestinal digestion, with and without cola jelly, and the digestate applied to Caco-2 cells. Both alginate and cola jelly significantly reduced iron uptake into the cells, by 34% (p=0.009) and 35% (p=0.003) respectively. The combination of cola jelly and calcium produced a very low ferritin response, 16.5% (p<0.001) of that observed with ferrous gluconate alone. The results of these studies demonstrate that alginate beads are not a useful delivery system for soluble salts of iron for the purpose of food fortification

High-resolution computed tomography reconstructions of invertebrate burrow systems

The architecture of biogenic structures can be highly influential in determining species contributions to major soil and sediment processes, but detailed 3-D characterisations are rare and descriptors of form and complexity are lacking. Here we provide replicate high-resolution micro-focus computed tomography (μ-CT) data for the complete burrow systems of three co-occurring, but functionally contrasting, sediment-dwelling inter-tidal invertebrates assembled alone, and in combination, in representative model aquaria. These data (≤2,000 raw image slices aquarium−1, isotropic voxel resolution, 81 μm) provide reference models that can be used for the development of novel structural analysis routines that will be of value within the fields of ecology, pedology, geomorphology, palaeobiology, ichnology and mechanical engineering. We also envisage opportunity for those investigating transport networks, vascular systems, plant rooting systems, neuron connectivity patterns, or those developing image analysis or statistics related to pattern or shape recognition. The dataset will allow investigators to develop or test novel methodology and ideas without the need to generate a complete three-dimensional computation of exemplar architecture

Thermodynamics of Higher Spin Black Holes in AdS3_3

We discuss the thermodynamics of recently constructed three-dimensional higher spin black holes in SL(N,R)\times SL(N,R) Chern-Simons theory with generalized asymptotically-anti-de Sitter boundary conditions. From a holographic perspective, these bulk theories are dual to two-dimensional CFTs with W_N symmetry algebras, and the black hole solutions are dual to thermal states with higher spin chemical potentials and charges turned on. Because the notion of horizon area is not gauge-invariant in the higher spin theory, the traditional approaches to the computation of black hole entropy must be reconsidered. One possibility, explored in the recent literature, involves demanding the existence of a partition function in the CFT, and consistency with the first law of thermodynamics. This approach is not free from ambiguities, however, and in particular different definitions of energy result in different expressions for the entropy. In the present work we show that there are natural definitions of the thermodynamically conjugate variables that follow from careful examination of the variational principle, and moreover agree with those obtained via canonical methods. Building on this intuition, we derive general expressions for the higher spin black hole entropy and free energy which are written entirely in terms of the Chern-Simons connections, and are valid for both static and rotating solutions. We compare our results to other proposals in the literature, and provide a new and efficient way to determine the generalization of the Cardy formula to a situation with higher spin charges.Comment: 30 pages, PDFLaTeX; v2: typos corrected, explicit expressions for the free energy adde

Gene variant effects across sodium channelopathies predict function and guide precision therapy

Pathogenic variants in the voltage-gated sodium channel gene family (SCNs) lead to early onset epilepsies, neurodevelopmental disorders, skeletal muscle channelopathies, peripheral neuropathies and cardiac arrhythmias. Disease-associated variants have diverse functional effects ranging from complete loss-of-function to marked gain-of-function. Therapeutic strategy is likely to depend on functional effect. Experimental studies offer important insights into channel function, but are resource intensive and only performed in a minority of cases. Given the evolutionarily conserved nature of the sodium channel genes we investigated whether similarities in biophysical properties between different voltage-gated sodium channels can predict function and inform precision treatment across sodium channelopathies. We performed a systematic literature search identifying functionally assessed variants in any of the nine voltage-gated sodium channel genes until 28 April 2021. We included missense variants that had been electrophysiologically characterised in mammalian cells in whole-cell patch-clamp recordings. We performed an alignment of linear protein sequences of all sodium channel genes and correlated variants by their overall functional effect on biophysical properties. Of 951 identified records, 437 sodium channel-variants met our inclusion criteria and were reviewed for functional properties. Of these, 141 variants were epilepsy-associated (SCN1/2/3/8A), 79 had a neuromuscular phenotype (SCN4/9/10/11A), 149 were associated with a cardiac phenotype (SCN5/10A) and 68 (16%) were considered benign. We detected 38 missense variant pairs with an identical disease-associated variant in a different sodium channel gene. 35 out of 38 of those pairs resulted in similar functional consequences indicating up to 92% biophysical agreement between corresponding sodium channel variants (odds ratio = 11.3; 95% CI = 2.8 to 66.9; P < 0.001). Pathogenic missense variants were clustered in specific functional domains, whereas population variants were significantly more frequent across non conserved domains (odds ratio = 18.6; 95% CI = 10.9 to 34.4; P < 0.001). Pore-loop regions were frequently associated with loss-of-function (LoF) variants, whereas inactivation sites were associated with gain-of-function (GoF; odds ratio = 42.1, 95% CI = 14.5 to 122.4; P < 0.001), whilst variants occurring in voltage-sensing regions comprised a range of gain- and loss-of-function effects. Our findings suggest that biophysical characterisation of variants in one SCN-gene can predict channel function across different SCN-genes where experimental data are not available. The collected data represent the first GoF versus LoF topological map of SCN proteins indicating shared patterns of biophysical effects aiding variant analysis and guiding precision therapy. We integrated our findings into a free online webtool to facilitate functional sodium channel gene variant interpretation (http://SCN-viewer.broadinstitute.org)

SCN1A variants from bench to bedside-improved clinical prediction from functional characterization

Variants in the SCN1A gene are associated with a wide range of disorders including genetic epilepsy with febrile seizures plus (GEFS+), familial hemiplegic migraine (FHM), and the severe childhood epilepsy Dravet syndrome (DS). Predicting disease outcomes based on variant type remains challenging. Despite thousands of SCN1A variants being reported, only a minority has been functionally assessed. We review the functional SCN1A work performed to date, critically appraise electrophysiological measurements, compare this to in silico predictions, and relate our findings to the clinical phenotype. Our results show, regardless of the underlying phenotype, that conventional in silico software correctly predicted benign from pathogenic variants in nearly 90%, however was unable to differentiate within the disease spectrum (DS vs. GEFS+ vs. FHM). In contrast, patch‐clamp data from mammalian expression systems revealed functional differences among missense variants allowing discrimination between disease severities. Those presenting with milder phenotypes retained a degree of channel function measured as residual whole‐cell current, whereas those without any whole‐cell current were often associated with DS (p = .024). These findings demonstrate that electrophysiological data from mammalian expression systems can serve as useful disease biomarker when evaluating SCN1A variants, particularly in view of new and emerging treatment options in DS

AdS/BCFT Correspondence for Higher Curvature Gravity: An Example

We consider the effects of higher curvature terms on a holographic dual description of boundary conformal field theory. Specifically, we consider three-dimensional gravity with a specific combination of Ricci tensor square and curvature scalar square, so called, new massive gravity. We show that a boundary entropy and an entanglement entropy are given by similar expression with those of the Einstein gravity case when we introduce an {\it effective} Newton's constant and an {\it effective} cosmological constant. We also show that the holographic g-theorem still holds in this extension, and we give some comments about the central charge dependence of boundary entropy in the holographic construction. In the same way, we consider new type black holes and comment on the boundary profile. Moreover, we reproduce these results through auxiliary field formalism in this specific higher curvature gravity.Comment: 27pages, minor corrections, accepted in JHE