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Far more publications are available for osteoarthritis of the knee than of the hip. Recognizing this research gap, the Arthritis Foundation, in partnership with the Hospital for Special Surgery, convened an in-person meeting of thought leaders to review the state of the science of and clinical approaches to hip osteoarthritis. This article summarizes the recommendations and clinical research gaps gleaned from 5 presentations given in the “how hip osteoarthritis begins” session of the 2023 Hip Osteoarthritis Clinical Studies Conference, which took place on February 17 and 18, 2023, in New York City.

ObjectiveTo summarize proceedings of a workshop convened to discuss the current state of science in the disease of osteoarthritis (OA), identify the knowledge gaps, and examine the developmental and regulatory challenges in bringing these products to market.DesignSummary of the one-day workshop held virtually on June 22nd, 2021.ResultsSpeakers selected by the Planning Committee presented data on the current approach to assessment of OA therapies, biomarkers in OA drug development, and the assessment of disease progression and long-term benefit.ConclusionsDemonstrated by numerous failed clinical trials, OA is a challenging disease for which to develop therapeutics. The challenge is magnified by the slow time of onset of disease and the need for clinical trials of long duration and/or large sample size to demonstrate the effect of an intervention. The OA science community, including academia, pharmaceutical companies, regulatory agencies, and patient communities, must continue to develop and test better clinical endpoints that meaningfully reflect disease modification related to long-term patient benefit.

A microfabricated flow cytometer was used to demonstrate multiplexed detection of bacteria and toxins using fluorescent coded microspheres. Antibody-coated microspheres bound biothreat targets in a sandwich immunoassay format. The microfluidic cytometer focused the mierospheres in three dimensions within the laser interrogation region using passive groove structures to surround the sample stream with sheath fluid. Optical analysis at four different wavelengths identified the coded microspheres and quantified target bound by the presence of phycoerythrin tracer. The multiplexed assays in the microflow cytometer had performance approaching that of a commercial benchtop flow cytometer. The respective limits of detection for bacteria (Escherichia coli, Listeria, and Salmonella) were found to be [10.sup.3], [10.sup.5], and [10.sup.4] cfu/ mL for the microflow cytometer and [10.sup.3], [10.sup.6], and [10.sup.5] cfu/mL for the commercial system. Limits of detection for the toxins (cholera toxin, staphylococcal enterotoxin B, and ricin) were 1.6, 0.064, and 1.6 ng/mL for the microflow cytometer and 1.6, 0.064, and 8.0 ng/mL for the commercial system.

Chiral molecular squares based on [M(dppe)](super 2+) metallocorners (M = Pd or Pt, and dppe = bis-(diphenylphosphino)ethane) and new angular bipyridine bridging ligands derived form the 1,1'-binaphthyl framework were readily assembled and characterized by a variety of techniques including infrared, UV-vis, circular dichroism (CD), and NMR spectroscopy, and ESI mass spectrometry.

A variety of ortho-, meta-, and para-substituted (-H, -F, -Cl, -C[F.sub.3], -CN (meta and para only), -C[H.sub.3], -OC[H.sub.3], and -N[O.sub.2]) acetophenone oximes were synthesized and studied using laser flash photolysis (LFP) and steady-state photolysis experiments in acetonitrile with chloranil as the photosensitizer. In addition, semi-empirical (AM1) calculations were performed on the neutral species, the radical cations, and the corresponding iminoxyl radicals. The data was analyzed in terms of the electrochemical peak potentials of the oximes, the quenching rates of triplet chloranil (LFP), the calculated ionization potentials, and the measured conversions of the oximes in the steady-state photolysis experiments. Photolysis of the oximes in the presence of chloranil results in the formation of the chloranil radical anion, which reacts rapidly with the oxime radical cation to form the semiquinone radical and an iminoxyl radical. Evidence for the formation of the chloranil radical anion and the semiquinone radical was obtained from LFP studies. The measured quenching rates from the LFP studies represent the rates of electron transfer from the oximes to triplet chloranil. This data was correlated to various radical and polar substituent constants. The Hammett studies suggest that steric, polar, and radical effects are important for ortho-substituted acetophenone oximes, polar effects are important for para-substituted oximes, and radical stabilization is more important than polar effects for the meta-substituted substrates. The calculated ionization potentials of the oximes show an excellent correlation with the measured quenching rates supporting the electron transfer pathway. On the basis of calculated charge densities, we conclude that the measured substituent effects are transition state effects rather than ground state effects. At this point all of the available data suggests that the conversion of the oximes is controlled by two energetically opposing reactions, namely oxidation of the neutral oxime, which is favorable for oximes with electron-donating substituents, and deprotonation of the oxime radical cation, which is favorable for oximes with electron-withdrawing substituents. The overall result is a reaction with little selectivity as far as substituent effects are concerned. Key words: oxime, radical cation, iminoxyl radical, electron transfer, substituent effect.

The synthesis and characterization of hybrid mesoporous silica nanosphere (MSN-Gd)-based magnetic resonance (MR) contrast agent and its applications in in vitro and in vivo MR imaging are described. The studies have shown that MSN-Gd is a very efficient [T.sub.1] contrast agent for intravascular MR imaging and an excellent [T.sub.2] contrast agent for MR imaging of soft tissues when applied at a higher dosage.

Electrostatic layer by layer (LbL) self-assembly is used to construct multifunctional nanoparticles (MFNPs) with both magnetic resonance and optical imaging capabilities. The LbL self assembly strategy affords MFNPs with extraordinarily high MR relaxivities and provides an efficient means for noncovalent functionalization of MFNPs with affinity molecules.