Insulin, Ascorbate, and Glucose Have a Much Greater Influence Than Transferrin and Selenous Acid on the In Vitro Growth of Engineered Cartilage in Chondrogenic Media

The primary goal of this study was to characterize the response of chondrocyte-seeded agarose constructs to varying concentrations of several key nutrients in a chondrogenic medium, within the overall context of optimizing the key nutrients and the placement of nutrient channels for successful growth of cartilage tissue constructs large enough to be clinically relevant in the treatment of osteoarthritis (OA). To this end, chondrocyte-agarose constructs (phi4x2.34 mm, 30x106 cells/mL) were subjected to varying supplementation levels of insulin (0× to 30× relative to standard supplementation), transferrin (0x to 30x), selenous acid (0x to 10x), ascorbate (0x to 30x), and glucose (0x to 3x). The quality of resulting engineered tissue constructs was evaluated by their compressive modulus (E-Y), tensile modulus (E+Y), hydraulic permeability (k), and content of sulfated glycosaminoglycans (sGAG) and collagen (COL); DNA content was also quantified. Three control groups from two separate castings of constructs (1x concentrations of all medium constituents) were used. After 42 days of culture, values in each of these controls were, respectively, E-Y=518 plus or minus 78, 401 plus or minus 113, 236 plus or minus 67 kPa; E+Y=1420 plus or minus 430, 1140 plus or minus 490, 1240 plus or minus 280 kPa; k=2.3 plus or minus 0.8x10-3, 5.4 plus or minus 7.0x10-3, 3.3 plus or minus 1.3x10-3 mm4/N times s; sGAG=7.8 plus or minus 0.3, 6.3 plus or minus 0.4, 4.1 plus or minus 0.5%/ww; COL=1.3 plus or minus 0.2, 1.1 plus or minus 0.3, 1.4 plus or minus 0.4%/ww; and DNA=11.5 plus or minus 2.2, 12.1 plus or minus 0.6, 5.2 plus or minus 2.8 μg/disk. The presence of insulin and ascorbate was essential, but their concentrations may drop as low as 0.3x without detrimental effects on any of the measured properties; excessive supplementation of ascorbate (up to 30x) was detrimental to E-Y, and 30x insulin was detrimental to both E+Y and E-Y. The presence of glucose was similarly essential, and matrix elaboration was significantly dependent on its concentration (p less than 10-6), with loss of functional properties, composition, and cellularity observed at less than or equal to 0.3x; excessive glucose supplementation (up to 3x) showed no detrimental effects. In contrast, transferrin and selenous acid had no influence on matrix elaboration. These findings suggest that adequate distributions of insulin, ascorbate, and glucose, but not necessarily of transferrin and selenous acid, must be ensured within large engineered cartilage constructs to produce a viable substitute for joint tissue lost due to OA

Search for heavy resonances decaying to two Higgs bosons in final states containing four b quarks

A search is presented for narrow heavy resonances X decaying into pairs of Higgs bosons (H) in proton-proton collisions collected by the CMS experiment at the LHC at root s = 8 TeV. The data correspond to an integrated luminosity of 19.7 fb(-1). The search considers HH resonances with masses between 1 and 3 TeV, having final states of two b quark pairs. Each Higgs boson is produced with large momentum, and the hadronization products of the pair of b quarks can usually be reconstructed as single large jets. The background from multijet and t (t) over bar events is significantly reduced by applying requirements related to the flavor of the jet, its mass, and its substructure. The signal would be identified as a peak on top of the dijet invariant mass spectrum of the remaining background events. No evidence is observed for such a signal. Upper limits obtained at 95 confidence level for the product of the production cross section and branching fraction sigma(gg -> X) B(X -> HH -> b (b) over barb (b) over bar) range from 10 to 1.5 fb for the mass of X from 1.15 to 2.0 TeV, significantly extending previous searches. For a warped extra dimension theory with amass scale Lambda(R) = 1 TeV, the data exclude radion scalar masses between 1.15 and 1.55 TeV

Measurement of the top quark mass using charged particles in pp collisions at root s=8 TeV

Peer reviewe

Efficacy and safety of two neutralising monoclonal antibody therapies, sotrovimab and BRII-196 plus BRII-198, for adults hospitalised with COVID-19 (TICO): a randomised controlled trial

We aimed to assess the efficacy and safety of two neutralising monoclonal antibody therapies (sotrovimab [Vir Biotechnology and GlaxoSmithKline] and BRII-196 plus BRII-198 [Brii Biosciences]) for adults admitted to hospital for COVID-19 (hereafter referred to as hospitalised) with COVID-19. In this multinational, double-blind, randomised, placebo-controlled, clinical trial (Therapeutics for Inpatients with COVID-19 [TICO]), adults (aged ≥18 years) hospitalised with COVID-19 at 43 hospitals in the USA, Denmark, Switzerland, and Poland were recruited. Patients were eligible if they had laboratory-confirmed SARS-CoV-2 infection and COVID-19 symptoms for up to 12 days. Using a web-based application, participants were randomly assigned (2:1:2:1), stratified by trial site pharmacy, to sotrovimab 500 mg, matching placebo for sotrovimab, BRII-196 1000 mg plus BRII-198 1000 mg, or matching placebo for BRII-196 plus BRII-198, in addition to standard of care. Each study product was administered as a single dose given intravenously over 60 min. The concurrent placebo groups were pooled for analyses. The primary outcome was time to sustained clinical recovery, defined as discharge from the hospital to home and remaining at home for 14 consecutive days, up to day 90 after randomisation. Interim futility analyses were based on two seven-category ordinal outcome scales on day 5 that measured pulmonary status and extrapulmonary complications of COVID-19. The safety outcome was a composite of death, serious adverse events, incident organ failure, and serious coinfection up to day 90 after randomisation. Efficacy and safety outcomes were assessed in the modified intention-to-treat population, defined as all patients randomly assigned to treatment who started the study infusion. This study is registered with ClinicalTrials.gov, NCT04501978. Between Dec 16, 2020, and March 1, 2021, 546 patients were enrolled and randomly assigned to sotrovimab (n=184), BRII-196 plus BRII-198 (n=183), or placebo (n=179), of whom 536 received part or all of their assigned study drug (sotrovimab n=182, BRII-196 plus BRII-198 n=176, or placebo n=178; median age of 60 years [IQR 50–72], 228 [43%] patients were female and 308 [57%] were male). At this point, enrolment was halted on the basis of the interim futility analysis. At day 5, neither the sotrovimab group nor the BRII-196 plus BRII-198 group had significantly higher odds of more favourable outcomes than the placebo group on either the pulmonary scale (adjusted odds ratio sotrovimab 1·07 [95% CI 0·74–1·56]; BRII-196 plus BRII-198 0·98 [95% CI 0·67–1·43]) or the pulmonary-plus complications scale (sotrovimab 1·08 [0·74–1·58]; BRII-196 plus BRII-198 1·00 [0·68–1·46]). By day 90, sustained clinical recovery was seen in 151 (85%) patients in the placebo group compared with 160 (88%) in the sotrovimab group (adjusted rate ratio 1·12 [95% CI 0·91–1·37]) and 155 (88%) in the BRII-196 plus BRII-198 group (1·08 [0·88–1·32]). The composite safety outcome up to day 90 was met by 48 (27%) patients in the placebo group, 42 (23%) in the sotrovimab group, and 45 (26%) in the BRII-196 plus BRII-198 group. 13 (7%) patients in the placebo group, 14 (8%) in the sotrovimab group, and 15 (9%) in the BRII-196 plus BRII-198 group died up to day 90. Neither sotrovimab nor BRII-196 plus BRII-198 showed efficacy for improving clinical outcomes among adults hospitalised with COVID-19. US National Institutes of Health and Operation Warp Spee

Search for supersymmetry in the multijet and missing transverse momentum final state in pp collisions at 13 TeV

A search for new physics is performed based on all-hadronic events with large missing transverse momentum produced in proton-proton collisions at sqrt(s)=13 TeV. The data sample, corresponding to an integrated luminosity of 2.3 inverse femtobarns, was collected with the CMS detector at the CERN LHC in 2015. The data are examined in search regions of jet multiplicity, tagged bottom quark jet multiplicity, missing transverse momentum, and the scalar sum of jet transverse momenta. The observed numbers of events in all search regions are found to be consistent with the expectations from standard model processes. Exclusion limits are presented for simplified supersymmetric models of gluino pair production. Depending on the assumed gluino decay mechanism, and for a massless, weakly interacting, lightest neutralino, lower limits on the gluino mass from 1440 to 1600 GeV are obtained, significantly extending previous limits

Search for top squark pair production in compressed-mass-spectrum scenarios in proton-proton collisions at sqrt(s) = 8 TeV using the alphaT variable

An inclusive search is performed for supersymmetry in final states containing jets and an apparent imbalance in transverse momentum, ptvecmiss, due to the production of unobserved weakly interacting particles in pp collisions at a centre-of-mass energy of 8 TeV. The data, recorded with the CMS detector at the CERN LHC, correspond to an integrated luminosity of 18.5 inverse femtobarns. The dimensionless kinematic variable alphaT is used to discriminate between events with genuine ptvecmiss associated with unobserved particles and spurious values of ptvecmiss arising from jet energy mismeasurements. No excess of event yields above the expected standard model backgrounds is observed. The results are interpreted in terms of constraints on the parameter space of several simplified models of supersymmetry that assume the pair production of top squarks. The search provides sensitivity to a broad range of top squark decay modes, including the two-body decay top squark to c chi0, where c is a charm quark and chi0 is the lightest neutralino, as well as the four-body decay top squark to b f bar-f' chi0, where b is a bottom quark and f and bar-f' are fermions produced in the decay of an intermediate off-shell W boson. These modes dominate in scenarios in which the top squark and lightest neutralino are nearly degenerate in mass. For these modes, top squarks with masses as large as 260 and 230 GeV are excluded, respectively, for the two- and four-body decays

Multiplicity and rapidity dependence of strange hadron production in pp, pPb, and PbPb collisions at the LHC

Measurements of strange hadron (K0s, Lambda + anti-Lambda, and Xi+ + Xi-) transverse momentum spectra in pp, pPb, and PbPb collisions are presented over a wide range of rapidity and event charged-particle multiplicity. The data were collected with the CMS detector at the CERN LHC in pp collisions at sqrt(s) = 7 TeV, pPb collisions at sqrt(s[NN]) = 5.02 TeV, and PbPb collisions at sqrt(s[NN]) = 2.76 TeV. The average transverse kinetic energy is found to increase with multiplicity, at a faster rate for heavier strange particle species in all systems. At similar multiplicities, the difference in average transverse kinetic energy between different particle species is observed to be larger for pp and pPb events than for PbPb events. In pPb collisions, the average transverse kinetic energy is found to be slightly larger in the Pb-going direction than in the p-going direction for events with large multiplicity. The spectra are compared to models motivated by hydrodynamics

Measurements of the associated production of a Z boson and b jets in pp collisions at s\sqrt{s} = 8 TeV

Measurements of the associated production of a Z boson with at least one jet originating from a b quark in proton-proton collisions at $\sqrt{s}$ = 8 TeV are presented. Differential cross sections are measured with data collected by the CMS experiment corresponding to an integrated luminosity of 19.8 inverse femtobarns. Z bosons are reconstructed through their decays to electrons and muons. Cross sections are measured as a function of observables characterizing the kinematics of the b jet and the Z boson. Ratios of differential cross sections for the associated production with at least one b jet to the associated production with any jet are also presented. The production of a Z boson with two b jets is investigated, and differential cross sections are measured for the dijet system. Results are compared to theoretical predictions, testing two different flavour schemes for the choice of initial-state partons