Inter- and intra-rater reliabilities of the Beighton Score compared to the Contompasis Score to assess Generalised Joint Hypermobility

Objectives: Generalized Joint Hypermobility [GJH] is a common connective tissue disorder associated with a range of musculoskeletal complaints. An effective screening tool to assess GJH may influence our understanding and choice of management. Diagnosis is clinical, using tools such as the Beighton Hypermobility Score and the Contompasis Scoring System. The comparable reliability of these tools has not been previously reported. The aim of the present study was to compare the intra- and the inter-rater reliability of the Beighton Score to the Contompasis Score to assess GJH. Methods: This was an observational study assessing 36 pain-free participants; 27 females and nine males; aged 18–32 years. Participants were assessed in random order, by two researchers over two sessions to determine intra- and inter-rater analyses. Intraclass Correlation Coefficient [ICC] and weighted Kappa statistics were used to calculate the level of agreement. Results: The intra- [ICC: 0.71–0.82] and the inter- [ICC: 0.72–0.80] rater reliability of the Beighton Score was substantial to almost perfect. The Contompasis Score displayed substantial to almost perfect intra-rater [ICC: 0.73–0.82] reliability and moderate to substantial inter-rater [ICC: 0.58–0.62] reliability. Conclusions: The present study provides an indication of the measurement capabilities of the Beighton and Contompasis Scores. The Beighton score appears to be superior compared with the Contompasis score particularly based on inter-rater reliability

Coupling dynamics of a geared multibody system supported by Elastohydrodynamic lubricated cylindrical joints

A comprehensive computational methodology to study the coupling dynamics of a geared multibody system supported by ElastoHydroDynamic (EHD) lubricated cylindrical joints is proposed throughout this work. The geared multibody system is described by using the Absolute-Coordinate-Based (ACB) method that combines the Natural Coordinate Formulation (NCF) describing rigid bodies and the Absolute Nodal Coordinate Formulation (ANCF) characterizing the flexible bodies. Based on the finite-short bearing approach, the EHD lubrication condition for the cylindrical joints supporting the geared system is considered here. The lubrication forces developed at the cylindrical joints are obtained by solving the Reynolds’ equation via the finite difference method. For the evaluation of the normal contact forces of gear pair along the Line Of Action (LOA), the time-varying mesh stiffness, mesh damping and Static Transmission Error (STE) are utilized. The time-varying mesh stiffness is calculated by using the Chaari’s methodology. The forces of sliding friction along the Off-Line-Of-Action (OLOA) are computed by using the Coulomb friction models with a time-varying coefficient of friction under the EHD lubrication condition of gear teeth. Finally, two numerical examples of application are presented to demonstrate and validate the proposed methodology.National Natural Science Foundations of China under Grant 11290151, 11221202 and 11002022, Beijing Higher Education Young Elite Teacher Project under Grant YETP1201

Rapid growth and high cloud-forming potential of anthropogenic sulfate aerosol in a thermal power plant plume during COVID lockdown in India

The COVID lockdown presented an interesting opportunity to study the anthropogenic emissions from different sectors under relatively cleaner conditions in India. The complex interplays of power production, industry, and transport could be dissected due to the significantly reduced influence of the latter two emission sources. Here, based on measurements of cloud condensation nuclei (CCN) activity and chemical composition of atmospheric aerosols during the lockdown, we report an episodic event resulting from distinct meteorological conditions. This event was marked by rapid growth and high hygroscopicity of new aerosol particles formed in the SO2 plume from a large coal-fired power plant in Southern India. These sulfate-rich particles had high CCN activity and number concentration, indicating high cloud-forming potential. Examining the sensitivity of CCN properties under relatively clean conditions provides important new clues to delineate the contributions of different anthropogenic emission sectors and further to understand their perturbations of past and future climate forcing

The delivery of personalised, precision medicines via synthetic proteins

Introduction: The design of advanced drug delivery systems based on synthetic and su-pramolecular chemistry has been very successful. Liposomal doxorubicin (Caelyx®), and liposomal daunorubicin (DaunoXome®), estradiol topical emulsion (EstrasorbTM) as well as soluble or erodible polymer systems such as pegaspargase (Oncaspar®) or goserelin acetate (Zoladex®) represent considerable achievements. The Problem: As deliverables have evolved from low molecular weight drugs to biologics (currently representing approximately 30% of the market), so too have the demands made of advanced drug delivery technology. In parallel, the field of membrane trafficking (and endocytosis) has also matured. The trafficking of specific receptors i.e. material to be recycled or destroyed, as well as the trafficking of protein toxins has been well characterized. This, in conjunction with an ability to engineer synthetic, recombinant proteins provides several possibilities. The Solution: The first is using recombinant proteins as drugs i.e. denileukin diftitox (Ontak®) or agalsidase beta (Fabrazyme®). The second is the opportunity to use protein toxin architecture to reach targets that are not normally accessible. This may be achieved by grafting regulatory domains from multiple species to form synthetic proteins, engineered to do multiple jobs. Examples include access to the nucleocytosolic compartment. Herein the use of synthetic proteins for drug delivery has been reviewed

SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion

The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era

SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion

The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era

Macroprolactin; a Frequent Cause of Misdiagnosed Hyperprolactinemia in Clinical Practice

Abstract Introduction: Macroprolactin is a significant cause of misdiagnosis, unnecessary investigation, and inappropriate treatment in patients with hyperprolactinemia. Its frequency has not been clearly established due to technical difficulties in identifying it. Most laboratories and clinicians are unaware of macroprolactin interferences in prolactin assays. Materials and Methods: A comprehensive literature search was conducted on the websites of the National Library of Medicine (http://www.ncbl.nlm.nih.gov) and PubMed Central, the US National Library of Medicine's digital archive of life sciences literature (http://www.pubmedcentral.nih.gov/). The data were also looked for in relevant books and journal. Results: Macroprolactin is a non-bioactive prolactin isoform usually composed of a prolactin monomer and an IgG molecule having a prolonged clearance rate similar to that of immunoglobulins. This isoform is clinically non-reactive but it interferes with immunological assays used for the detection of prolactin. Conclusion: There is a need to understand and explore the recent progress in the diagnosis and pathophysiology of macroprolactinemia for improving patient care

Accurate loss modelling in the DCOPF calculation for power markets via static piecewise linear loss approximation based upon line loading classification

The objective of this paper is to explore a better curve fitting technique that can improve the power flow accuracy of the piecewise linear loss modelling in the DC optimal power flow (DCOPF) calculation. The refinement of the DCOPF model is carried out in view of a power market that employs the locational marginal pricing principle for market clearing, performs multiple settlements and issues financial transmission rights. The piecewise linear loss modelling exhibits a typical advantage over the conventional purely linearised loss modelling in terms of the risk hedging capability of financial transmission rights. Unlike the available piecewise linear loss models with static parameters, the static curve fitting technique proposed in this paper evaluates loss parameters by means of some weighted error minimisation based upon a binary classification of the line loading level. Detailed mathematical procedure is developed to obtain the solution of the proposed curve fitting optimisation problem. The power flow accuracies of different linear and piecewise linear loss models that are suitable for the specified market framework are assessed and compared. Extensive case studies are performed on a 118-bus, a 1354-bus, and a 2383-bus systems to justify the merit of the proposed piecewise linear loss modelling technique