Microfibrous Solid Dispersions of Poorly Water-Soluble Drugs Produced via Centrifugal Spinning: Unexpected Dissolution Behavior on Recrystallization

Temperature-controlled, solvent-free centrifugal spinning may be used as a means of rapid production of amorphous solid dispersions in the form of drug-loaded sucrose microfibers. However, due to the high content of amorphous sucrose in the formulations, such microfibers may be highly hygroscopic and unstable on storage. In this study, we explore both the effects of water uptake of the microfibers and the consequences of deliberate recrystallization for the associated dissolution profiles. The stability of sucrose microfibers loaded with three selected BCS class II model drugs (itraconazole (ITZ), olanzapine (OLZ), and piroxicam (PRX)) was investigated under four different relative humidity conditions (11, 33, 53, and 75% RH) at 25 °C for 8 months, particularly focusing on the effect of the highest level of moisture (75% RH) on the morphology, size, drug distribution, physical state, and dissolution performance of microfibers. While all samples were stable at 11% RH, at 33% RH the ITZ-sucrose system showed greater resistance against devitrification compared to the OLZ- and PRX-sucrose systems. For all three samples, the freshly prepared microfibers showed enhanced dissolution and supersaturation compared to the drug alone and physical mixes; surprisingly, the dissolution advantage was largely maintained or even enhanced (in the case of ITZ) following the moisture-induced recrystallization under 75% RH. Therefore, this study suggests that the moisture-induced recrystallization process may result in considerable dissolution enhancement compared to the drug alone, while overcoming the physical stability risks associated with the amorphous state

Эпидемиология эндопротезирования тазобедренного и коленного суставов и перипротезной инфекции в Российской Федерации

Background. Since there is no national arthroplasty registry in the Russian Federation, the exact number of arthroplasty operations performed is unknown. Aim of the study to evaluate the epidemiology of primary, revision hip and knee arthroplasty and periprosthetic joint infection in Russian Federation. Materials and Methods. The inquires were made to 85 subjects, 73 federal state budget institutions and 30 private hospitals. Results. Answers were received from 76 subjects of Russian Federation, 41 federal and 18 private hospitals. The studied indicators revealed to be pretty much heterogenic. The decrease of operations number from 20% to 40% in subjects of Russian Federation due to SARS-CoV-2 pandemic forced us to make no analysis for these 2020 indicators in Russian Federation generally. 147 061 primary hip and knee arthroplasties were performed in 2019 in Russian Federaion. 7 770 revison hip and knee arthroplasties were done. 6 606 cases of severe orthopaedic implant-assosiated infection were cured including 4 282 cases post hip and knee arthroplasties that constitutes 2,91 % from primary arthroplasties. Conclusions. The frequency of periprosthetic joint infection in Russian Federation correlates to the world data. High complexity for patients routing with implant-assosiated infection and strong demand for Federal Center of implant-assosiated orthopaedic infection are revealed.Актуальность. Поскольку в Российской Федерации отсутствует национальный регистр артропластики, точное число выполненных операций эндопротезирования неизвестно. Цель изучить эпидемиологию эндопротезирования коленного и тазобедренного суставов, а также перипротезной инфекции (ППИ) в Российской Федерации (РФ). Материал и методы. Сделаны запросы в 85 субъектов, 73 федеральных государственных бюджетных учреждения и 30 частных учреждений здравоохранения. Результаты. Получены ответы из 76 субъектов РФ, 41 федерального и 18 частных учреждений здравоохранения. В 2020 г. установлена значительная гетерогенность изучаемых показателей: снижение числа операций составило от 20 до 40% в различных субъектах РФ в связи с пандемией SARS-CoV-2, поэтому показатели 2020 г. решено было не анализировать по России в целом. В 2019 г. в РФ выполнено 147 061 операций первичного эндопротезирования коленного и тазобедренного суставов, 7 770 ревизионных артропластик коленного и тазобедренного суставов. В 2019 г. пролечено 6 606 случаев тяжелой ортопедической имплантат-ассоциированной инфекции, в т.ч. 4 282 случая после эндопротезирования коленного и тазобедренного суставов, что составляет 2,91% от первичных эндопротезирований. Заключение. Частота ППИ в РФ коррелирует с мировыми данными. Выявлена высокая сложность маршрутизации пациентов с имплантат-ассоциированной инфекцией и стойкая необходимость в создании федерального центра по лечению имплантат-ассоциированной ортопедической инфекции

Charmless hadronic decays B→PP,PV,VVB \to PP, PV, VV and new physics effects in the general two-Higgs doublet models

Based on the low-energy effective Hamiltonian with the generalized factorization, we calculate the new physics contributions to the branching ratios of the two-body charmless hadronic decays of $B_u$ and $B_d$ mesons induced by the new gluonic and electroweak charged-Higgs penguin diagrams in the general two-Higgs doublet models (models I, II and III). Within the considered parameter space, we find that: (a) the new physics effects from new gluonic penguin diagrams strongly dominate over those from the new $\gamma$- and $Z^0$- penguin diagrams; (b) in models I and II, new physics contributions to most studied B meson decay channels are rather small in size: from -15% to 20%; (c) in model III, however, the new physics enhancements to the penguin-dominated decay modes can be significant, $\sim (30 -200)$, and therefore are measurable in forthcoming high precision B experiments; (d) the new physics enhancements to ratios {\cal B}(B \to K \etap) are significant in model III, $\sim (35 -70)$, and hence provide a simple and plausible new physics interpretation for the observed unexpectedly large B \to K \etap decay rates; (e) the theoretical predictions for ${\cal B}(B \to K^+ \pi)$ and ${\cal B}(B \to K^0 \pi^+)$ in model III are still consistent with the data within $2\sigma$ errors; (f) the significant new physics enhancements to the branching ratios of $B \to K^0 \pi^0, K^* \eta, K^{*+} \pi^-, K^+ \phi, K^{*0} \omega, K^{*+} \phi$ and $K^{*0} \phi$ decays are helpful to improve the agreement between the data and the theoretical predictions; (g) the theoretical predictions of ${\cal B}(B \to PP, PV, VV)$ in the 2HDM's are generally consistent with experimental measurements and upper limits ($90$)Comment: 55 pages, Latex file, 17 PS and EPS figures. With minor corrections, final version to be published in Phys.Rev. D. Repot-no: PKU-TH-2000-4

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

Search for a W' boson decaying to a bottom quark and a top quark in pp collisions at sqrt(s) = 7 TeV

Results are presented from a search for a W' boson using a dataset corresponding to 5.0 inverse femtobarns of integrated luminosity collected during 2011 by the CMS experiment at the LHC in pp collisions at sqrt(s)=7 TeV. The W' boson is modeled as a heavy W boson, but different scenarios for the couplings to fermions are considered, involving both left-handed and right-handed chiral projections of the fermions, as well as an arbitrary mixture of the two. The search is performed in the decay channel W' to t b, leading to a final state signature with a single lepton (e, mu), missing transverse energy, and jets, at least one of which is tagged as a b-jet. A W' boson that couples to fermions with the same coupling constant as the W, but to the right-handed rather than left-handed chiral projections, is excluded for masses below 1.85 TeV at the 95% confidence level. For the first time using LHC data, constraints on the W' gauge coupling for a set of left- and right-handed coupling combinations have been placed. These results represent a significant improvement over previously published limits.Comment: Submitted to Physics Letters B. Replaced with version publishe

Jet size dependence of single jet suppression in lead-lead collisions at sqrt(s(NN)) = 2.76 TeV with the ATLAS detector at the LHC

Measurements of inclusive jet suppression in heavy ion collisions at the LHC provide direct sensitivity to the physics of jet quenching. In a sample of lead-lead collisions at sqrt(s) = 2.76 TeV corresponding to an integrated luminosity of approximately 7 inverse microbarns, ATLAS has measured jets with a calorimeter over the pseudorapidity interval |eta| < 2.1 and over the transverse momentum range 38 < pT < 210 GeV. Jets were reconstructed using the anti-kt algorithm with values for the distance parameter that determines the nominal jet radius of R = 0.2, 0.3, 0.4 and 0.5. The centrality dependence of the jet yield is characterized by the jet "central-to-peripheral ratio," Rcp. Jet production is found to be suppressed by approximately a factor of two in the 10% most central collisions relative to peripheral collisions. Rcp varies smoothly with centrality as characterized by the number of participating nucleons. The observed suppression is only weakly dependent on jet radius and transverse momentum. These results provide the first direct measurement of inclusive jet suppression in heavy ion collisions and complement previous measurements of dijet transverse energy imbalance at the LHC.Comment: 15 pages plus author list (30 pages total), 8 figures, 2 tables, submitted to Physics Letters B. All figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/HION-2011-02

Search for the standard model Higgs boson decaying into two photons in pp collisions at sqrt(s)=7 TeV

A search for a Higgs boson decaying into two photons is described. The analysis is performed using a dataset recorded by the CMS experiment at the LHC from pp collisions at a centre-of-mass energy of 7 TeV, which corresponds to an integrated luminosity of 4.8 inverse femtobarns. Limits are set on the cross section of the standard model Higgs boson decaying to two photons. The expected exclusion limit at 95% confidence level is between 1.4 and 2.4 times the standard model cross section in the mass range between 110 and 150 GeV. The analysis of the data excludes, at 95% confidence level, the standard model Higgs boson decaying into two photons in the mass range 128 to 132 GeV. The largest excess of events above the expected standard model background is observed for a Higgs boson mass hypothesis of 124 GeV with a local significance of 3.1 sigma. The global significance of observing an excess with a local significance greater than 3.1 sigma anywhere in the search range 110-150 GeV is estimated to be 1.8 sigma. More data are required to ascertain the origin of this excess.Comment: Submitted to Physics Letters

Measurement of the polarisation of W bosons produced with large transverse momentum in pp collisions at sqrt(s) = 7 TeV with the ATLAS experiment

This paper describes an analysis of the angular distribution of W->enu and W->munu decays, using data from pp collisions at sqrt(s) = 7 TeV recorded with the ATLAS detector at the LHC in 2010, corresponding to an integrated luminosity of about 35 pb^-1. Using the decay lepton transverse momentum and the missing transverse energy, the W decay angular distribution projected onto the transverse plane is obtained and analysed in terms of helicity fractions f0, fL and fR over two ranges of W transverse momentum (ptw): 35 < ptw < 50 GeV and ptw > 50 GeV. Good agreement is found with theoretical predictions. For ptw > 50 GeV, the values of f0 and fL-fR, averaged over charge and lepton flavour, are measured to be : f0 = 0.127 +/- 0.030 +/- 0.108 and fL-fR = 0.252 +/- 0.017 +/- 0.030, where the first uncertainties are statistical, and the second include all systematic effects.Comment: 19 pages plus author list (34 pages total), 9 figures, 11 tables, revised author list, matches European Journal of Physics C versio

Observation of a new chi_b state in radiative transitions to Upsilon(1S) and Upsilon(2S) at ATLAS

The chi_b(nP) quarkonium states are produced in proton-proton collisions at the Large Hadron Collider (LHC) at sqrt(s) = 7 TeV and recorded by the ATLAS detector. Using a data sample corresponding to an integrated luminosity of 4.4 fb^-1, these states are reconstructed through their radiative decays to Upsilon(1S,2S) with Upsilon->mu+mu-. In addition to the mass peaks corresponding to the decay modes chi_b(1P,2P)->Upsilon(1S)gamma, a new structure centered at a mass of 10.530+/-0.005 (stat.)+/-0.009 (syst.) GeV is also observed, in both the Upsilon(1S)gamma and Upsilon(2S)gamma decay modes. This is interpreted as the chi_b(3P) system.Comment: 5 pages plus author list (18 pages total), 2 figures, 1 table, corrected author list, matches final version in Physical Review Letter