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

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

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

Integrated energy and transmission pricing

This paper introduces the concept of transmission side bidding for availing power transmission services through a market mechanism. The transmission side bidding, in essence, refers to the direct market participation of transmission line owners for selling their line capacities with appropriate price offers. The transmission offers are submitted to the centralized auction conducted by the independent system operator for carrying out dispatch scheduling or for the issuance of transmission rights. Those are jointly cleared along with other bids and offers, and bid-consistent prices are established by means of marginal pricing. The uncertainty that gets involved in revenues or payments of market players because of the conventional transmission pricing is, therefore, eliminated. By recognizing the criticality of power flow interactions between different transmission lines, the auction participation of transmission line owners is suitably regulated. The issuance of financial transmission rights (FTRs) is supplemented by assigning counterflow flowgate rights to the transmission line owners so as to ensure revenue adequate FTR settlement. Detailed case studies are performed to verify the utility of the proposed transmission pricing methodology

Implementation of lossy FTRs for perfect risk hedging under the marginal loss pricing

In this study, a market framework is proposed for the practical implementation of lossy financial transmission rights (FTRs). The advantage of lossy FTRs over conventional FTRs is that the lossy FTRs can be settled directly according to locational marginal prices (LMPs) without requiring any LMP decomposition. Therefore, the price risk for a forward contract can be perfectly hedged if the power transaction involved perfectly matches the corresponding FTR. Although proposed long back, lossy FTRs still did not find an entry to the market because of the prejudice of market complexity and inefficiency. The principal aim of this study is, thus, to create the necessary environment so as to make those fine risk-hedging tools available in the market. First of all, a suitable format for forward contracts is prescribed to enable proper utilisation of lossy FTRs. The detailed lossy FTR auction model is prepared based upon a suitable optimal power flow (OPF) formulation. In addition, the implementation of lossy FTRs is shown for an AC-DC system by appropriately modelling the DC-line power flow behaviour according to the chosen OPF framework. The lossy FTR auction model prepared is thoroughly verified for the FTR issuance as per the market expectations