Treatment of osteoporosis: recommendations and reality

То achieve optimal results of treatment osteoporosis, not only effective medication, but also patients' adherence to treatment is required. Aim: to assess rates and factors of patients' adherence to prescribed treatment of osteoporosis. Methods: the study included 340 residents of the Sverdlovsk Region, Russia, who had previously been diagnosed and consulted regarding osteoporosis. Letters with questionnaires and envelopes for the answers were sent to all patients at least in 3 months after the treatment had been prescribed. Questionnaires included questions about treatment, risk factors, knowledge about osteoporosis. Reply rate was 62,5% (182 persons). Replies of these 182 patients were processed. Results: 7 (3,8%) patients did not begin recommended treatment at all. By the date of inquiry in 15 (8,2%) persons the treatment was terminated, while 160 (87,9%) patients continued with their treatment. Recommended pathogenic treatment of osteoporosis was taken by 116 (63,7%) patients, but only 72 (39,6%) of them received it on a regular basis. Factors of better patients' adherence to pathogenetic treatment of osteoporosis were: disability (OR 2,3:95% Cl 1,22 — 4,32), long duration of osteoporosis (OR 2,54:95% Cl 1,23 — 5,25), fracture history (OR 2,06:95% Cl 1,11 — 3,81) and back pain and height loss due to vertebral fractures (OR 4,68; 95% Cl 2,34 — 9,39). Conclusion: Patients' adherence to pharmacotherapy of osteoporosis is low in general clinical practice. Only 39,6% patients received pathogenetic medication on a regular basis. Fracture history, back pain and height loss are associated with better adherence to treatment Thus, patients with complicated osteoporosis are more adherent to treatment than those with preclinical stage of osteoporosis.Для достижения оптимальных результатов терапии больных остеопорозом (ОП) важно помимо доказанной эффективности препаратов соблюдение приверженности пациентов лечению. Целью данной работы являлась оценка приверженности больных ОП лечению и факторы, влияющие на нее. Материал и методы. В исследование включены пациенты Свердловской области с установленным диагнозом ОП и рекомендованным лечением, при условии, что после консультации и назначения лечения прошло, по крайней мере, 3 месяца. Всем проконсультированным пациентам была проведена почтовая рассылка анкет с вопросами о проводимом лечении ОП, о факторах риска ОП и его клинических проявлениях, а также с вопросами, оценивающими знания об ОП. Всего было разослано 340 писем. Отклик выборки составил 62,5%. В обработку включены ответы 182 чел. Результаты Из 182 опрошенных пациентов рекомендованное лечение не начали только 7 чел. (3,8%). 15 пациентов (8,2%) прекратили лечение. 160 чел. (87,9%) продолжали лечение на момент опроса. Препараты патогенетического действия принимали 116 чел. (63,7%), но только 72 чел. (39,6%) лечились препаратами патогенетического действия регулярно. На прием препаратов патогенетического действия влияли: наличие группы инвалидности (ОШ = 2,3: 95% ДИ=1,22 — 4,32, продолжительность заболевания после постановки диагноза ОШ=2,54; 95% ДИ=1,23 — 5,25, наличие переломов костей в анамнезе при низком уровне травмы, 0ш=2,06; 95% ДИ=1,11 — 3,81, а также клинические признаки переломов позвонков (боль в спине и снижение роста) ОШ=4,68; 95% ДИ=2,34 — 9,39. Таким образом, приверженность пациентов с ОП лечению низкая, только 39,6% пациентов принимают регулярно препараты патогенетического действия. Пациенты с переломами костей в анамнезе при низком уровне травмы и с клиническими симптомами переломов позвонков более привержены лечению, чем пациенты с доклинической стадией ОП

АЛГОРИТМ ВИЗНАЧЕННЯ ПРОМІЖНИХ ВУЗЛІВ НАВАНТЕЖЕННЯ РАДІАЛЬНИХ РОЗПОДІЛЬЧИХ МЕРЕЖ

An algorithm based on the method of potential surface is developed for determining intermediate load centers of radial distribution networksРазработан алгоритм определения промежуточных узлов загрузки радиальных распределительных сетей на основе метода потенциальной поверхностиНа основі методу потенційної поверхні розроблено алгоритм визначення проміжних вузлів навантаження радіальних розподільчих мереж

Coupling carbon nanotube mechanics to a superconducting circuit

The quantum behaviour of mechanical resonators is a new and emerging field driven by recent experiments reaching the quantum ground state. The high frequency, small mass, and large quality-factor of carbon nanotube resonators make them attractive for quantum nanomechanical applications. A common element in experiments achieving the resonator ground state is a second quantum system, such as coherent photons or superconducting device, coupled to the resonators motion. For nanotubes, however, this is a challenge due to their small size. Here, we couple a carbon nanoelectromechanical (NEMS) device to a superconducting circuit. Suspended carbon nanotubes act as both superconducting junctions and moving elements in a Superconducting Quantum Interference Device (SQUID). We observe a strong modulation of the flux through the SQUID from displacements of the nanotube. Incorporating this SQUID into superconducting resonators and qubits should enable the detection and manipulation of nanotube mechanical quantum states at the single-phonon level

Peculiarities of the Weyl - Wigner - Moyal formalism for scalar charged particles

A description of scalar charged particles, based on the Feshbach-Villars formalism, is proposed. Particles are described by an object that is a Wigner function in usual coordinates and momenta and a density matrix in the charge variable. It is possible to introduce the usual Wigner function for a large class of dynamical variables. Such an approach explicitly contains a measuring device frame. From our point of view it corresponds to the Copenhagen interpretation of quantum mechanics. It is shown how physical properties of such particles depend on the definition of the coordinate operator. The evolution equation for the Wigner function of a single-charge state in the classical limit coincides with the Liouville equation. Localization peculiarities manifest themselves in specific constraints on possible initial conditions.Comment: 16 pages, 2 figure

Quantitative predictions on auxin-induced polar distribution of PIN proteins during vein formation in leaves

The dynamic patterning of the plant hormone auxin and its efflux facilitator the PIN protein are the key regulator for the spatial and temporal organization of plant development. In particular auxin induces the polar localization of its own efflux facilitator. Due to this positive feedback auxin flow is directed and patterns of auxin and PIN arise. During the earliest stage of vein initiation in leaves auxin accumulates in a single cell in a rim of epidermal cells from which it flows into the ground meristem tissue of the leaf blade. There the localized auxin supply yields the successive polarization of PIN distribution along a strand of cells. We model the auxin and PIN dynamics within cells with a minimal canalization model. Solving the model analytically we uncover an excitable polarization front that triggers a polar distribution of PIN proteins in cells. As polarization fronts may extend to opposing directions from their initiation site we suggest a possible resolution to the puzzling occurrence of bipolar cells, such we offer an explanation for the development of closed, looped veins. Employing non-linear analysis we identify the role of the contributing microscopic processes during polarization. Furthermore, we deduce quantitative predictions on polarization fronts establishing a route to determine the up to now largely unknown kinetic rates of auxin and PIN dynamics.Comment: 9 pages, 4 figures, supplemental information included, accepted for publication in Eur. Phys. J.

Challenges in QCD matter physics - The Compressed Baryonic Matter experiment at FAIR

Substantial experimental and theoretical efforts worldwide are devoted to explore the phase diagram of strongly interacting matter. At LHC and top RHIC energies, QCD matter is studied at very high temperatures and nearly vanishing net-baryon densities. There is evidence that a Quark-Gluon-Plasma (QGP) was created at experiments at RHIC and LHC. The transition from the QGP back to the hadron gas is found to be a smooth cross over. For larger net-baryon densities and lower temperatures, it is expected that the QCD phase diagram exhibits a rich structure, such as a first-order phase transition between hadronic and partonic matter which terminates in a critical point, or exotic phases like quarkyonic matter. The discovery of these landmarks would be a breakthrough in our understanding of the strong interaction and is therefore in the focus of various high-energy heavy-ion research programs. The Compressed Baryonic Matter (CBM) experiment at FAIR will play a unique role in the exploration of the QCD phase diagram in the region of high net-baryon densities, because it is designed to run at unprecedented interaction rates. High-rate operation is the key prerequisite for high-precision measurements of multi-differential observables and of rare diagnostic probes which are sensitive to the dense phase of the nuclear fireball. The goal of the CBM experiment at SIS100 (sqrt(s_NN) = 2.7 - 4.9 GeV) is to discover fundamental properties of QCD matter: the phase structure at large baryon-chemical potentials (mu_B > 500 MeV), effects of chiral symmetry, and the equation-of-state at high density as it is expected to occur in the core of neutron stars. In this article, we review the motivation for and the physics programme of CBM, including activities before the start of data taking in 2022, in the context of the worldwide efforts to explore high-density QCD matter.Comment: 15 pages, 11 figures. Published in European Physical Journal

Effect of prior treatments on selinexor, bortezomib, and dexamethasone in previously treated multiple myeloma

Therapeutic regimens for previously treated multiple myeloma (MM) may not provide prolonged disease control and are often complicated by significant adverse events, including peripheral neuropathy. In patients with previously treated MM in the Phase 3 BOSTON study, once weekly selinexor, once weekly bortezomib, and 40 mg dexamethasone (XVd) demonstrated a significantly longer median progression-free survival (PFS), higher response rates, deeper responses, a trend to improved survival, and reduced incidence and severity of bortezomib-induced peripheral neuropathy when compared with standard twice weekly bortezomib and 80 mg dexamethasone (Vd). The pre-specified analyses described here evaluated the influence of the number of prior lines of therapy, prior treatment with lenalidomide, prior proteasome inhibitor (PI) therapy, prior immunomodulatory drug therapy, and prior autologous stem cell transplant (ASCT) on the efficacy and safety of XVd compared with Vd. In this 1:1 randomized study, enrolled patients were assigned to receive once weekly oral selinexor (100 mg) with once weekly subcutaneous bortezomib (1.3 mg/m2) and 40 mg per week dexamethasone (XVd) versus standard twice weekly bortezomib and 80 mg per week dexamethasone (Vd). XVd significantly improved PFS, overall response rate, time-to-next-treatment, and showed reduced all grade and grade ≥ 2 peripheral neuropathy compared with Vd regardless of prior treatments, but the benefits of XVd over Vd were more pronounced in patients treated earlier in their disease course who had either received only one prior therapy, had never been treated with a PI, or had prior ASCT. Treatment with XVd improved outcomes as compared to Vd regardless of prior therapies as well as manageable and generally reversible adverse events. XVd was associated with clinical benefit and reduced peripheral neuropathy compared to standard Vd in previously treated MM. These results suggest that the once weekly XVd regimen may be optimally administered to patients earlier in their course of disease, as their first bortezomib-containing regimen, and in those relapsing after ASCT. Trial registration: ClinicalTrials.gov (NCT03110562). Registered 12 April 2017. https://clinicaltrials.gov/ct2/show/NCT03110562

Conference of Soviet and American Jurists on the Law of the Sea and the Protection of the Marine Environment

Included in the papers for the Conference of Soviet and American Jurists on the Law of the Sea and the Protection of the Marine Environment: Introduction by Milton Katz and Richard R. Baxter, p. 1 Freedom of Scientific Research in the World Ocean by A.F. Vysotsky, p. 7 The International Law of Scientific Research in the Oceans by Richard R. Baxter, p. 27 Responsibility and Liability for Harm to the Marine Environment by Robert E. Stein, p. 41 Liability for Marine Environment Pollution Damage in Contemporary International Sea Law by A. L. Makovsky, p. 59 Protection of the Marine Environment from Pollution by Richard A. Frank, p. 73 The Freedom of Navigation and the Problem of Pollution of the Marine Environment by V. A. Kiselev, p. 93 The Freedom of Navigation Under International Law by William E. Butler, p. 107 International Fisheries Management Without Global Agreement: United States Policies and Their Impact on the Soviet Union by H. Gary Knight, p. 119 Some Biological Background for International Legal Acts on Rational Utilization of the Living Resources of the World Ocean by P. A. Moiseev, p. 143 An International Regime for the Seabed Beyond National Jurisdiction by Thomas M. Franck, p. 151 Settlement of Disputes Under the Law of Ocean Use, with Particular Reference to Environmental Protection by John Lawrence Hargrove, p. 18

Observation of a single protein by ultrafast X-ray diffraction

The idea of using ultrashort X-ray pulses to obtain images of single proteins frozen in time has fascinated and inspired many. It was one of the arguments for building X-ray free-electron lasers. According to theory1, the extremely intense pulses provide sufficient signal to dispense with using crystals as an amplifier, and the ultrashort pulse duration permits capturing the diffraction data before the sample inevitably explodes2. This was first demonstrated on biological samples a decade ago on the giant mimivirus3. Since then a large collaboration4 has been pushing the limit of the smallest sample that can be imaged5,6. The ability to capture snapshots on the timescale of atomic vibrations, while keeping the sample at room temperature, may allow probing the entire conformational phase space of macromolecules. Here we show the first observation of an X-ray diffraction pattern from a single protein, that of Escherichia coli GroEL which at 14 nm in diameter7 is the smallest biological sample ever imaged by X-rays, and demonstrate that the concept of diffraction before destruction extends to single proteins. From the pattern, it is possible to determine the approximate orientation of the protein. Our experiment demonstrates the feasibility of ultrafast imaging of single proteins, opening the way to single-molecule time-resolved studies on the femtosecond timescale