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The actual problem of the possibility of using the equations of state for the gas phase of natural gas at temperatures below 250 K is considered. To solve it, the compressibility coefficients of natural gas obtained experimentally with high accuracy are required. The technique was developed and experimental study was carried out of compressibility factor aiming expanding temperature range of the state equations GERG-2004 and AGA8-DC92. The proposed technique is based on the fact that to assess the applicability of the equation of state, it is sufficient to obtain the relative value of the compressibility coefficient and not to determine its absolute value. The technique does not require complex equipment and provides high accuracy. The technique was tested on nitrogen, argon, air and methane. Uncertainty of determination of the compressibility factor is not greater than 0.1 %. For two different compositions of natural gas, obtained experimental data were demonstrated that the equations of state GERG-2004 and AGA8-92DC provide uncertainty of the calculation of the compressibility coefficient within 0.1 % in the temperature range from 220 K to 250 K and pressure below 5 MPa.

Multiple Input Multiple Output (MIMO) technology is widely used in modern IEEE radio access systems. There is a tendency to increase the number of antennas, which is also confirmed by the development of MIMO technology in mobile communication systems of 3GPP standards. Requirements for modern radio communication systems are constantly increasing. As the radio frequency spectrum becomes increasingly scarce, it becomes increasingly difficult to transmit large amounts of information by expanding the frequency channel bandwidth. Therefore, the use of MIMO technology to increase the spectral and energy efficiency of communication systems is relevant. In 5G systems, Massive MIMO technology is used, when using which the number of antennas is measured in tens and hundreds. The characteristics of various versions of MIMO technology implemented in the existing standards 802.11n, 802.11ac, 802.11ax, as well as in the promising standard 802.11be (6G systems) are described in detail. Technologies of directional transmission, spatial multiplexing, selection of antennas as particular cases of precoding are considered. Trends of MIMO technology development in wireless communication systems are shown.

According to official data, up to 40 million cases of infectious diseases are registered in Russia annually, half of them in children. Vaccination can significantly reduce the incidence of various infectious diseases, such as diphtheria, measles, tetanus, poliomyelitis, etc. However, development of new safe and effective vaccine preparations is still relevant. One of the approaches to their development is vaccines based on various viral vectors, including recombinant human adenoviruses. Such vaccines have shown their safety and effectiveness in preclinical and clinical trials, including trials in the Russian Federation.

Background The pandemic of the new coronavirus infection has challenged the medical community for quickly finding and implementing effective methods of treatment In the absence of a vaccine or specific therapy with proven effectiveness, the usage of convalescent plasma can be the one of perspective methods An important aspect of this technology is the efficient and safe preparation of convalescent plasma To date, in the world literature there are practically no publications about donor recruitment and the specifics of the preparation of convalescent plasma Purpose of the research Presentation of the experience of organizing a workflow for recruiting donors and stockpiling of convalescent plasma with a high titer of virus-neutralizing antibodies to SARS-CoV-2 Methods The analysis of the work of the Blood Service of the Moscow Department of Health for stockpiling of COVID-19 convalescent plasma has been executed In total it has been stockpiled 1240 doses The normative documentation has been developed by a working group on the basis of the current federal legislation of Russian federation and been approved by the Moscow Department of Health The titer of neutralizing antibodies (VNA) has been determined as the basic method for assessing the immunological viability of convalescent plasma The main characteristics of donors, the characteristics of the disease course, the results of preliminary testing for the presence of specific antibodies by ELISA and CLIA methods has been compared with VNA titers in the stockpiled convalescent plasma Results Due to a Moscow Health Department’s order No 325 dated 01 04 2020 (a basic local regulatory document) it has been developed a regulation for the stockpiling, examination, storage, safety and transfering of fresh frozen pathogen-reduced plasma of COVID-19 convalescent donors to medical organizations of the Moscow Health Department For arranging an interaction with donors it has been created a call-center For effective preliminary selection, it has been formed a donor characteristics list, which has been combined with screening of specific antibodies by ELISA and CLIA methods Conclusions Developed a system of recruiting donors and procurement process of convalescent plasma for treatment СOVID-19, which includes the necessary regulations, algorithms for the selection and recruitment of donors, the registry of donors and recipients, algorithms, efficiency and safety of convalescent plasma Обоснование Пандемия новой коронавирусной инфекции поставила перед медицинским сообществом задачу быстрого поиска и внедрения эффективных методик лечения В условиях отсутствия вакцины и средств специфической терапии с доказанной эффективностью в качестве одной из перспективных методик рассматривается трансфузия реконвалесцентной плазмы (РП) Важным аспектом данной технологии является заготовка эффективного и безопасного компонента На сегодняшний день публикации по рекрутингу доноров и особенностях заготовки РП в мировой литературе практически отсутствуют Цель исследования - Анализ опыта организации рабочего процесса по привлечению доноров и заготовке РП с высоким титром вируснейтрализующих антител к SARS-CoV-2 Методы Проведен анализ работы Службы крови Департамента здравоохранения г Москвы (ДЗМ) по заготовке РП COVID-19 Всего заготовлено 1240 доз Нормативная документация разработана рабочей группой на основании действующего федерального законодательства и утверждена ДЗМ Как базовая методика оценки иммунологической состоятельности РП, определен титр вируснейтрализующих антител (ВНА) Проведено сопоставление основных характеристик доноров, особенностей течения заболевания, результатов предварительного тестирования на наличие специфических антител методами ИФА и ИХЛА с титрами ВНА заготовленной РП Результаты Работа по заготовке, обследованию, хранению, обеспечению безопасности и передаче в медицинские организации ДМЗ свежезамороженной патогенредуцированной плазмы доноров-реконвалесцентов COVID-19 была организована на основании приказа ДЗМ от 01 04 2020 № 325 как базового локального нормативного документа Для оптимальной коммуникации с состоявшимися донорами и привлечения реконвалесцентов использовались ресурсы колл-центра Для эффективного предварительного отбора доноров применялись анализ характеристик донора (плазма с наибольшими значениями титра ВНА ожидаема от доноров-мужчин, переболевших с признаками явной вирусной пневмонии) и результаты скрининга специфических антител методами ИФА и ИХЛА Заключение Разработана система обеспечения рекрутинга доноров и процесса заготовки РП для лечения СOVID-19, включающая необходимые нормативные документы, алгоритмы отбора и привлечения доноров, реестр доноров и реципиентов, алгоритмы обеспечения эффективности и безопасности РП

An excessive inflammatory response to SARS-CoV-2 is thought to be a major cause of disease severity and mortality in patients with COVID-19. Longitudinal analysis of cytokine release can expand our understanding of the initial stages of disease development and help to identify early markers serving as predictors of disease severity. In this study, we performed a comprehensive analysis of 46 cytokines (including chemokines and growth factors) in the peripheral blood of a large cohort of COVID-19 patients (n=444). The patients were classified into five severity groups. Longitudinal analysis of all patients revealed two groups of cytokines, characterizing the “early” and “late” stages of the disease course and the switch between type 1 and type 2 immunity. We found significantly increased levels of cytokines associated with different severities of COVID-19, and levels of some cytokines were significantly higher during the first three days from symptom onset (DfSO) in patients who eventually required intensive care unit (ICU) therapy. Additionally, we identified nine cytokines, TNF-α, IL-10, MIG, IL-6, IP-10, M-CSF, G-CSF, GM-CSF, and IFN-α2, that can be used as good predictors of ICU requirement at 4-6 DfSO.

Despite the measures taken worldwide, COVID-19 pandemic still progresses. While efficient antiviral drugs are not yet widely available, vaccination is the best option to control the infection rate. Although this option is obvious in case of COVID-19–naïve individuals, it is still unclear when individuals who have recovered from a previous SARS-CoV-2 infection should be vaccinated and whether the vaccination raises immune responses against the coronavirus and its novel variants. Here we measured the dynamics of the antibody and T-cell responses, as well as virus neutralizing activity (VNA) in serum against two SARS-CoV-2 variants, B.1.1.1 and B.1.617.2, among 84 individuals with different COVID-19 status who were vaccinated with Sputnik Light vaccine. We showed that vaccination of individuals previously exposed to the virus considerably boosts the existing immune response. In these individuals, RBD-specific IgG titers and VNA in serum were already elevated on the 7th day after vaccination, while COVID-19–naïve individuals developed the antibody response and VNA mainly 21 days post–vaccination. Additionally, we found a strong correlation between RBD-specific IgG titers and VNA in serum, and according to these data vaccination may be recommended if the RBD-specific IgG titers drop to 142.7 BAU/mL or below. In summary, the results of the study demonstrate that vaccination is beneficial both for COVID-19–naïve and recovered individuals, especially since it raises serum VNA against the B.1.617.2 variant – one of four the SARS-CoV-2 variants of concern.

ObjectivesVaccination remains the most effective response to the COVID-19 pandemic. Most vaccines use two-dose regimens. In turn, single-dose vaccines also have high potential, since, on the one hand, they simplify the vaccination program, make it more accessible and convenient for more people around the world, and on the other hand, they are better suited for subsequent revaccination. However, there is not enough data on the effectiveness of single-dose vaccine variants against new genetic lines to assess their current potential. It is not clear how much a single dose of immunization protects against the globally dominant delta variant. In this work, we investigated the effectiveness of a single dose vaccine (Sputnik Light, the first component of Sputnik V vaccine) against the Delta variant in Moscow.MethodsTo assess the effectiveness of one dose of viral vector vaccine based on rAd26 against the delta variant in Moscow, we used data from the Moscow registries of vaccination against COVID-19 and the incidence of COVID-19. The availability of data on the number of seropositive residents of Moscow made it possible to consider the size of the immune layer formed because of a previous COVID-19 disease or vaccination. To calculate the effectiveness, the proportion of COVID-19 cases among those vaccinated with a single dose and the proportion of cases among those who were not vaccinated in July 2021.ResultsOur data indicate that throughout July 2021, the dominant variant of the coronavirus at the level of 99.5% in Moscow was the SARS-CoV-2 delta variant and its subsidiary lines. Considering the immune layer of 46% allowed us to calculate the effectiveness of a one-shot vaccine against the delta variant in Moscow during the first three months after vaccination at the level of 69.85% (95% confidence interval [CI], 64.08 to 74.70). In the 18-29-year-old group, the overall vaccine efficacy against the delta variant was 88.61%, in the 18-59 group - 75.28%. Sputnik Light demonstrates higher efficacy against Delta variant than many two-shot vaccines.ConclusionThe results indicate a high efficacy of a single immunization first component of Sputnik V vaccine against delta variant among young and middle-aged people, at least during the first 3 months after receiving the one-shot vaccine.

In horses, Clostridium perfringens is associated with acute and fatal enterocolitis, which is caused by a beta toxin (CPB), and myonecrosis, which is caused by an alpha toxin (CPA). Although the most effective way to prevent these diseases is through vaccination, specific clostridial vaccines for horses against C. perfringens are not widely available. The aim of this study was to pioneer the immunization of horses with three different concentrations (100, 200 and 400 µg) of C. perfringens recombinant alpha (rCPA) and beta (rCPB) proteins, as well as to evaluate the humoral immune response over 360 days. Recombinant toxoids were developed and applied to 50 horses on days 0 and 30. Those vaccines attempted to stimulate the production of alpha antitoxin (anti-CPA) and beta antitoxin (anti-CPB), in addition to becoming innocuous, stable and sterile. There was a reduction in the level of neutralizing anti-CPA and anti-CPB antibodies following the 60th day, therefore, the concentrations of 200 and 400 µg capable of inducing a detectable humoral immune response were not determined until day 180. In practical terms, 200 µg is possibly the ideal concentration for use in the veterinary industry’s production of vaccines against the action of C. perfringens in equine species.

Despite advances in traditional lithium-ion batteries in the past decades, its high cost has always been a bottleneck for large-scale applications. In this work, we demonstrate it is possible to replace expensive cathodes such as LiCoO2 with inexpensive stainless steel to store energy via a stripping/deposition mechanism: during charging, the stainless-steel cathode removes charges by releasing metal ions into the electrolyte, and during discharge, the metal ions re-deposit on the electrode reversibly. An anion exchange membrane allows passage of anions to balance the charge and prevents cross-over of cations. We show here a battery with a stainless-steel cathode and a lithium metal anode with a high discharge voltage of 2.5 V and good reversibility. We also study the mechanism at the stainless-steel electrode, as well as the kinetics of the battery system. Our work can potentially reduce the cost of energy storage by turning common construction materials into cathode materials. In addition, a metal cathode undergoing stripping/deposition gives a theoretical energy density comparable to lithium-sulfur batteries and provides a new exciting direction for future energy storage development.

Background A heterologous recombinant adenovirus (rAd)-based vaccine, Gam-COVID-Vac (Sputnik V), showed a good safety profile and induced strong humoral and cellular immune responses in participants in phase 1/2 clinical trials. Here, we report preliminary results on the efficacy and safety of Gam-COVID-Vac from the interim analysis of this phase 3 trial. Methods We did a randomised, double-blind, placebo-controlled, phase 3 trial at 25 hospitals and polyclinics in Moscow, Russia. We included participants aged at least 18 years, with negative SARS-CoV-2 PCR and IgG and IgM tests, no infectious diseases in the 14 days before enrolment, and no other vaccinations in the 30 days before enrolment. Participants were randomly assigned (3:1) to receive vaccine or placebo, with stratification by age group. Investigators, participants, and all study staff were masked to group assignment. The vaccine was administered (0·5 mL/dose) intramuscularly in a prime-boost regimen: a 21-day interval between the first dose (rAd26) and the second dose (rAd5), both vectors carrying the gene for the full-length SARS-CoV-2 glycoprotein S. The primary outcome was the proportion of participants with PCR-confirmed COVID-19 from day 21 after receiving the first dose. All analyses excluded participants with protocol violations: the primary outcome was assessed in participants who had received two doses of vaccine or placebo, serious adverse events were assessed in all participants who had received at least one dose at the time of database lock, and rare adverse events were assessed in all participants who had received two doses and for whom all available data were verified in the case report form at the time of database lock. The trial is registered at ClinicalTrials.gov (NCT04530396). Findings Between Sept 7 and Nov 24, 2020, 21 977 adults were randomly assigned to the vaccine group (n=16 501) or the placebo group (n=5476). 19 866 received two doses of vaccine or placebo and were included in the primary outcome analysis. From 21 days after the first dose of vaccine (the day of dose 2), 16 (0·1%) of 14 964 participants in the vaccine group and 62 (1·3%) of 4902 in the placebo group were confirmed to have COVID-19; vaccine efficacy was 91·6% (95% CI 85·6–95·2). Most reported adverse events were grade 1 (7485 [94·0%] of 7966 total events). 45 (0·3%) of 16 427 participants in the vaccine group and 23 (0·4%) of 5435 participants in the placebo group had serious adverse events; none were considered associated with vaccination, with confirmation from the independent data monitoring committee. Four deaths were reported during the study (three [

Resistance to antibacterial therapy requires the discovery of new methods for the treatment of infectious diseases. Lactoferrin (LTF) is a well-known na&iuml, ve first-line defense protein. In the present study, we suggested the use of an adenoviral vector (Ad5) carrying the human gene encoding LTF for direct and cell-mediated gene therapy of maxillofacial area phlegmon in rats. Abscesses were developed by injection of the purulent peritoneal exudate in the molar region of the medial surface of the mandible. At 3&ndash, 4 days after phlegmon maturation, all rats received ceftriaxone and afterward were subcutaneously injected around the phlegmon with: (1) Ad5 carrying reporter gfp gene encoding green fluorescent protein (Ad5-GFP control group), (2) Ad5 carrying LTF gene (Ad5-LTF group), (3) human umbilical cord blood mononuclear cells (UCBC) transduced with Ad5-GFP (UCBC + Ad5-GFP group), and (4) UCBC transduced with Ad5-LTF (UCBC + Ad5-LTF group). Control rats developed symptoms considered to be related to systemic inflammation and were euthanized at 4&ndash, 5 days from the beginning of the treatment. Rats from therapeutic groups demonstrated wound healing and recovery from the fifth to seventh day based on the type of therapy. Histological investigation of cervical lymph nodes revealed purulent lymphadenitis in control rats and activated lymphatic tissue in rats from the UCBC + Ad5-LTF group. Our results propose that both approaches of LTF gene delivery are efficient for maxillofacial area phlegmon recovery in rats. However, earlier wound healing and better outcomes in cervical lymph node remodeling in the UCBC + Ad5-LTF group, as well as the lack of direct exposure of the viral vector to the organism, which may cause toxic and immunogenic effects, suggest the benefit of cell-mediated gene therapy.

Background: HIV infection is a known factor that aggravates the clinical course of many infectious diseases including COVID-19. The international guidance suggests that benefits from preventive SARS-CoV-2 vaccination using products with proven efficacy overweigh potential risks for HIV-infected people. However, there is little data on epidemiological assessment of COVID-19 vaccines efficacy among HIV-infected people. This paper provides preliminary assessment of Sputnik V (Gam-COVID-Vac) vaccine effectiveness in HIV-infected patients under antiretroviral therapy (ART) in Moscow. Methods: We performed a retrospective cohort study to assess the effectiveness of Sputnik V standard vaccination regimen in HIV-infected patients during spring-summer 2021, comparing SARS-CoV-2 PCR-positivity, hospitalization, and severe illness rates in vaccinated and unvaccinated subjects. The study included HIV-positive subjects on ART from Moscow City Center for AIDS Prevention and Control, using data from the Moscow COVID-19 Vaccination and COVID-19 incidence Registries. Vaccine effectiveness was calculated as (1-RR)*100%, where RR – is a risk ratio to contract SARS-CoV-2 in both unvaccinated and vaccinated individuals. 2021 spring data shows Sputnik V effectiveness against initial SARS-CoV-2 variant, while summer data are indicative of vaccine effectiveness against the Delta and its descendant lines. Results: The data obtained indicate that Sputnik V epidemiological effectiveness in the entire cohort of HIV-infected people on ART in Moscow was 76·33% (95% CI 69·84% – 81·43%). In the subgroup of HIV-infected patients with CD4+ T-cell count ≥ 350 cells/μl vaccine effectiveness was 79·42% (95% CI 72·54 – 84·57), preventing hospital admissions in 90·12% (95% CI 77·70 – 95·62) and protecting from the development of moderate-to-severe and severe disease in 97·06% (95% CI 78·93 – 99·59). During predominant circulation of the delta variant Sputnik V epidemiological effectiveness in subjects with CD4+ T-cells count ≥ 350 cells/μl was 65·35% (52·61% – 74·66%), preventing hospital admissions in 75·77% (95% CI 44·25 – 89·47) and protecting from the development of moderate-to-severe and severe disease in 93·05% (95% CI 49·51 – 99·04). Conclusion: The study demonstrated high epidemiological effectiveness of full immunization with Sputnik V in HIV-infected ART-treated patients with CD4 + T-cell counts ≥ 350 cells/μl. Moreover, the epidemiological effectiveness of vaccination was documented for both – the original and the delta SARS-CoV-2 variants, with the latter predominating in the Moscow region since June 2021. Although the efficiency of the vaccine declined in immunocompromised individuals (T-cell count < 350 cells/μl), it is still sufficient to recommend vaccination with Sputnik V of this cohort. Funding: Ministry of Health of Russia and Moscow Healthcare Department. Declaration of Interest: DVS, DYL and ALG report patents for a Sputnik V immunobiological expression vector, pharmaceutical agent, and its method of use to prevent COVID-19. All other authors declare no competing interests. Ethics Approval Statement: All information from the databases was anonymized before it was received by the research team. The study was submitted to the Local Ethics Committee of State Budgetary Healthcare Institution Infectious Diseases Hospital № 2 Moscow Health Department. The Committee concluded (Protocol № 11 of 04/10/2021) that the study does not use identifiable biological specimens and does not provide any confidential patient data. Therefore, according to the rules of the Local Ethics Committee and National standards, this project does not require ethical approval.

Background: While the world is experiencing another wave of COVID-19 pandemic, global vaccination program is hampered by obvious shortage in supply of licensed vaccines. Development of new vaccines that are easy to manufacture and administer is highly desirable to overcome hurdles in vaccine scaling up and distribution, especially in developing countries. In the effort to satisfy vaccine demands we developed a new single dose vaccine based on recombinant adenovirus type 26 (rAd26) vector carrying the gene for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein – “Sputnik Light”. Methods: We conducted an open label, two-stage, prospective, non-randomized phase I-II trial aimed to assess safety, tolerability and immunogenicity of “Sputnik Light” vaccine in a single center in Russia. Primary outcome measures were antigen-specific humoral immunity (Anti-RBD-SARS-Cov2 antibodies measured by ELISA on days 1, 10, 28, and 42) and safety (number of participants with adverse events monitored throughout the study). Secondary outcome measures were antigen-specific cellular immunity (measured by antigen-dependent CD4+ and CD8+ T-cell proliferation, number of antigen-specific interferon-γ-producing cells as well as interferon-γ concentration upon antigen restimulation) and change in neutralizing antibodies (measured in SARS-CoV-2 neutralization assay). The trial is registered at ClinicalTrials.gov (NCT04713488). Findings: Between January 14 and 27, 2021, 150 participants were screened, of whom 110 were enrolled. Most of solicited adverse reactions were mild (66.4% from all vaccinees), few were moderate (5.5%). No serious adverse events were detected. Assessment of Anti-RBD-SARS-Cov2 antibodies revealed group with pre-existing immunity to SARS-CoV-2. Upon this finding we separated all safety and immunogenicity data according to pre-existing immunity to SARS-Cov2. There were notable differences in the vaccine effects on immunogenicity by the groups. Vaccination of seropositive (N=14) volunteers rapidly boosted RBD-specific IgGs from reciprocal geometric mean titer (​GMT) 594.4 at a baseline up to 26899 comparing to 29.09 in seronegative group (N=96) by day 10. By day 42 seroconversion rate reached 100% (93/93) in seronegative group with GMT 1648. At the same time in seropositive group seroconversion rate by day 42 was 92.9% (13/14) with GMT 19986. Analysis of neutralizing antibodies to SARS-CoV-2 showed 81.7% (76/93) and 92.9% (13/14) seroconversion rates by day 42 with median reciprocal GMT 15.18 and 579.7 in the seronegative and seropositive groups, respectively. Each test to assess cell-mediated immune reactions was carried out on a separate group of 30 volunteers on day 10 upon vaccination. Antigen-specific T cell proliferation, formation of IFNy-producing cells, as well as IFNy secretion were detected in 96.7% (26/27), 96% (24/25) and 96% (24/25) seronegative and in 100% (3/3) 100% (5/5) and 100% (5/5) seropositive vaccinees, correspondingly. Interpretation: The single dose rAd26 vector-based COVID-19 vaccine “Sputnik Light” has a good safety profile and induced strong humoral and cellular immune responses both in seronegative and seropositive participants. Further investigation is needed to assess the effectiveness of this vaccine against COVID-19 used for primary and secondary vaccination. Clinical Trial Registration Details: The trial is registered at ClinicalTrials.gov (NCT04713488). Funding Information: Russian Direct Investment Fund. Declaration of Interests: OVZ, TAO, IVD, OP, DVS, DMG, ASD, AIT, DNS, IBE, EAT, AGB, ASE, FMI, NAN, NLL, ASS, SVB, BSN, DYL, ALG report patents for an immunobiological expression vector, pharmaceutical agent, and its method of use to prevent COVID-19. All other authors declare no competing interests. Ethics Approval Statement: The trial was approved by the local ethic committee and was conducted with the approval of the Ministry of Health of Russian Federation in compliance with International Conference on Harmonization and National Good Clinical Practice guidelines and Declaration of Helsinki.

Clostridium perfringens is considered one of the main causative agents of superacute enterocolitis, usually fatal in the equine species, due to the action of the β toxin, and is responsible for causing severe myonecrosis, by the action of the α toxin. The great importance of this agent in the equine economy is due to high mortality and lack of vaccines, which are the main form of prevention, which guarantee the immunization of this animal species. The aim of this study was to evaluate three different concentrations (100, 200 and 400μg) of C. perfringens α and β recombinant toxoids in equine immunization and to compare with a group vaccinated with a commercial toxoid. The commercial vaccine was not able to stimulate an immune response and the recombinant vaccine was able to induce satisfactory humoral immune response in vaccinated horses, proving to be an alternative prophylactic for C. perfringens infection. RESUMO: Clostridium perfringens é considerado um dos principais agentes causadores de enterocolites superagudas, geralmente fatais na espécie equina, devido à ação da toxina β, além de ser responsável por causar quadros graves de mionecrose, pela ação da toxina α. A grande importância desses agentes na equinocultura, deve-se a elevada mortalidade e a inexistência de vacinas, principal forma de prevenção, que garantam a imunização dessa espécie animal. O objetivo deste trabalho foi avaliar três diferentes concentrações (100, 200 e 400μg) dos toxóides recombinantes α e β de C. perfringens na imunização de equinos, bem como comparar com um grupo vacinado com um toxóide comercial. A vacina comercial não se mostrou capaz de estimular uma resposta imune e a vacina recombinante foi capaz de induzir resposta imune humoral satisfatória em equinos vacinados, provando ser uma alternativa profilática para infecção por C. Perfringens.

The Middle East Respiratory Syndrome (MERS) is an acute inflammatory disease of the respiratory system caused by the MERS-CoV coronavirus. The mortality rate for MERS is about 34.5%. Due to its high mortality rate, the lack of therapeutic and prophylactic agents, and the continuing threat of the spread of MERS beyond its current confines, developing a vaccine is a pressing task, because vaccination would help limit the spread of MERS and reduce its death toll. We have developed a combined vector vaccine for the prevention of MERS based on recombinant human adenovirus serotypes 26 and 5. Studies of its immunogenicity have shown that vaccination of animals (mice and primates) induces a robust humoral immune response that lasts for at least six months. Studies of the cellular immune response in mice after vaccination showed the emergence of a specific CD4+ and CD8+ T cell response. A study of the vaccine protectivity conducted in a model of transgenic mice carrying the human DPP4 receptor gene showed that our vaccination protected 100% of the animals from the lethal infection caused by the MERS-CoV virus (MERS-CoV EMC/2012, 100LD50 per mouse). Studies of the safety and tolerability of the developed vaccine in rodents, rabbits, and primates showed a good safety profile and tolerance in animals; they revealed no contraindications for clinical testing.

Induction of a robust and long-lived mucosal immune response during vaccination is critical to achieve protection against numerous pathogens. However, traditional injected vaccines are generally poor inducers of mucosal immunity. One of the effective strategies to improve vaccine efficacy is incorporation of adjuvant molecules that enhance and polarize adaptive immune reactions. Effects of Syk-coupled lectin receptor agonists as adjuvants to induce mucosal immune reactions during parenteral immunization are not fully studied. We now report that the agonists trehalose-6,6-dibehenate (TDB), curdlan, and furfurman, which stimulate Dectin-1, Dectin-2, and Mincle, respectively, activate transcription factors (NF-κB, NFAT, and AP-1) to various extents in murine RAW 264.7 macrophages, even though similar pathways are activated. The agonists also elicit differential expression of maturation markers in bone marrow-derived dendritic cells, as well as differential cytokine secretion from these cells and from splenic mononuclear cells. In vivo assays also show that agonists of Dectin-1 and Dectin-2, but not Mincle, induce heavy IgA secretion in intestinal mucosa even when delivered parenterally. Strikingly, this effect appears to be formulation-independent. Collectively, the data suggest that adjuvants based on Dectin-1 and Dectin-2 agonists may significantly improve the efficacy of parenteral vaccines by inducing robust local immune reactions in intestinal mucosa.

Desiccant dehumidification is an alternative solution for independently processing air humidity, which can simultaneously accommodate the sensible and latent heat loads even in high-humidity areas (e.g., Hong Kong). However, there is still a lack of comparative investigation in practical applications between the traditional condensation dehumidification and desiccant dehumidification, which is of great significance for revealing the effectiveness of desiccant dehumidifiers. Therefore, this study conducted on-site measurements in four different types of buildings. Moreover, the annual performance of different dehumidification solutions based on the set values of real buildings were simulated to further compare the dehumidification capacity, energy consumption, and cost performance. Results showed that the indoor humidity control of the measured buildings was substandard when using condensation dehumidification, and it was significantly improved after installing desiccant dehumidifiers. Compared with overcooling & reheating condensation dehumidification that achieved a similar humidity level, the annual energy savings of the desiccant dehumidification were respectively up to 4.9% and 7.7% for an office and a hotel based on the simulation results. The economic analysis indicated that desiccant dehumidification was more cost-effective than condensation dehumidification with overcooling & reheating. Finally, comprehensive evaluations were presented to facilitate the selection of dehumidification solutions.

The Ebola virus disease (EVD) is one of the most dangerous infections affecting humans and animals. The first EVD outbreaks occurred in 1976 in Sudan and Zaire. Since then, more than 20 outbreaks have occurred; the largest of which (2014-2016) evolved into an epidemic in West Africa and claimed the lives of more than 11,000 people. Although vaccination is the most effective way to prevent epidemics, there was no licensed vaccine for EVD at the beginning of the latest outbreak. The development of the first vaccines for EVD started in 1980 and has come a long technological way, from inactivated to genetically engineered vaccines based on recombinant viral vectors. This review focuses on virus-vectored Ebola vaccines that have demonstrated the greatest efficacy in preclinical trials and are currently under different phases of clinical trial. Particular attention is paid to the mechanisms of immune response development, which are important for protection from EVD, and the key vaccine parameters necessary for inducing long-term protective immunity against EVD.

OBJECTIVEThe most actively explored therapeutic strategy for overcoming spinal cord injury (SCI) is the delivery of genes encoding molecules that stimulate regeneration. In a mouse model of amyotrophic lateral sclerosis and in preliminary clinical trials in patients with amyotrophic lateral sclerosis, the combined administration of recombinant adenoviral vectors (Ad5-VEGF+Ad5-ANG) encoding the neurotrophic/angiogenic factors vascular endothelial growth factor (VEGF) and angiogenin (ANG) was found to slow the development of neurological deficits. These results suggest that there may be positive effects of this combination of genes in posttraumatic spinal cord regeneration. The objective of the present study was to determine the effects of Ad5-VEGF+Ad5-ANG combination therapy on motor function recovery and reactivity of astrocytes in a rat model of SCI.METHODSSpinal cord injury was induced in adult Wistar rats by the weight-drop method. Rats (n = 51) were divided into 2 groups: the experimental group (Ad5-VEGF+Ad5-ANG) and the control group (Ad5-GFP [green fluorescent protein]). Recovery of motor function was assessed using the Basso, Beattie, and Bresnahan scale. The duration and intensity of infectivity and gene expression from the injected vectors were assessed by immunofluorescent detection of GFP. Reactivity of glial cells was assessed by changes in the number of immunopositive cells expressing glial fibrillary acidic protein (GFAP), S100β, aquaporin 4 (AQP4), oligodendrocyte transcription factor 2, and chondroitin sulfate proteoglycan 4. The level of S100β mRNA expression in the spinal cord was estimated by real-time polymerase chain reaction.RESULTSPartial recovery of motor function was observed 30 days after surgery in both groups. However, Basso, Beattie, and Bresnahan scores were 35.9% higher in the Ad5-VEGF+Ad5-ANG group compared with the control group. Specific GFP signal was observed at distances of up to 5 mm in the rostral and caudal directions from the points of injection. A 1.5 to 2.0–fold increase in the number of GFAP+, S100β+, and AQP4+ cells was observed in the white and gray matter at a distance of up to 5 mm from the center of the lesion site in the caudal and rostral directions. At 30 days after injury, a 2-fold increase in S100β transcripts was observed in the Ad5-VEGF+Ad5-ANG group compared with the control group.CONCLUSIONSIntraspinal injection of recombinant adenoviral vectors encoding VEGF and ANG stimulates functional recovery after traumatic SCI. The increased number of S100β+ astrocytes induced by this approach may be a beneficial factor for maintaining the survival and function of neurons. Therefore, gene therapy with Ad5-VEGF+Ad5-ANG vectors is an effective therapeutic method for SCI treatment.

Ebola hemorrhagic fever, also known as Ebola virus disease or EVD, is one of the most dangerous viral diseases in humans and animals. In this open-label, dose-escalation clinical trial, we assessed the safety, side effects, and immunogenicity of a novel, heterologous prime-boost vaccine against Ebola, which was administered in 2 doses to 84 healthy adults of both sexes between 18 and 55 years. The vaccine consists of live-attenuated recombinant vesicular stomatitis virus (VSV) and adenovirus serotype-5 (Ad5) expressing Ebola envelope glycoprotein. The most common adverse event was pain at the injection site, although no serious adverse events were reported. The vaccine did not significantly impact blood, urine, and immune indices. Seroconversion rate was 100 %. Antigen-specific IgG geometric mean titer at day 42 was 3,277 (95 % confidence interval 2,401–4,473) in volunteers immunized at full dose. Neutralizing antibodies were detected in 93.1 % of volunteers immunized at full dose, with geometric mean titer 20. Antigen-specific response in peripheral blood mononuclear cells was also detected in 100 % of participants, as well as in CD4+ and CD8+ T cells in 82.8 % and 58.6 % of participants vaccinated at full dose, respectively. The data indicate that the vaccine is safe and induces strong humoral and cellular immune response in up to 100 % of healthy adult volunteers, and provide a rationale for testing efficacy in Phase III trials. Indeed, the strong immune response to the vaccine may elicit long-term protection. This trial was registered with grls.rosminzdrav.ru (No. 495*), and with zakupki.gov.ru (No. 0373100043215000055).

The aim of the work is to perform a quantitative assessment of the level of using the production potential in the regions of the Russian Federation over a long period of time. The theoretical base of the studied problem is considered. The author’s criteria for diagnosing the degree of developing advanced technologies are presented. Approbating the calculations was made on the basis of data from the official statistical reports of the Federal State Statistics Service. Tabular and graphical analysis methods are implemented. The territories that demonstrate high and extremely low results of implementing production capabilities and using high-tech technological solutions are identified. The scattergram of production indicators by region in the context of a separate federal district is presented. The tendency of strengthening interterritorial disproportions is substantiated. The possible causes of problems existing in socio-economic systems are disclosed. The general conclusions about the real level of engaging advanced technologies at the enterprises of the Russian Federation in the dynamic and spatial perspectives are formulated. The prerequisites for developing further research in the field of monitoring regional imbalances, working out additional combined indicators and studying the effectiveness of implementing production potential in the territories while transiting the national economic system to the course of modernization are identified.

In our research we compare various neural network architectures that are used for object detection and recognition. In this work vehicles and pedestrians are considered objects of interest. Modern artificial neural networks are able to detect and localize objects of known classes. This allows them to be used in various technical vision systems and video analysis systems. In this paper we compare three architectures (YOLO, Faster R-CNN, SSD) by the following criteria: processing speed, mAP, precision and recall.

In South Africa, the problem of service delivery cuts across all municipalities as manifested by citizen protests across the country on almost daily basis. To mitigate the costs associated with the protests, the South African government has placed emphasis on the role played by human resources management through instituting legislative frameworks, such as the the White Paper on Human Resource Management in the Public Service (1997). Despite this effort, the human resource management practices of municipalities continue to be criticized, by both municipal internal staff and citizenry. Service delivery in the South African context is regarded as one of the cornerstone indicators of how the government affords its citizens access to quality life as enshrined in its constitution. This paper is one of the studies based on the South African context attempting to explain the problem of service delivery by looking at perceived fairness in human resource management (HRM) practices by employees of municipalities and how such perceptions affect their motivation to work. Using the tenets of the organizational justice theory, the authors hypothesize that perceived HRM practices of municipalities can be predictors of employee motivation. Quantitative data collected from employees of nine randomly selected municipalities in the Free State Province are used to create indices for the different HRM practices as well as employee motivation. Significant correlation tests are performed. Results show a positive correlation between perceived fairness in the HRM practices of municipalities and employees’ motivation at .05 and .01 levels of significance. This means that fair HRM practices of municipalities promote employee motivation

We previously demonstrated that gene-modified umbilical cord blood mononuclear cells overexpressing a combination of recombinant neurotrophic factors are a promising therapeutic approach for cell-mediated gene therapy for neurodegenerative diseases, neurotrauma, and stroke. In this study, using a mini pig model of spinal cord injury, we proposed for the first time the use of gene-modified leucoconcentrate prepared from peripheral blood in the plastic blood bag for personalized ex vivo gene therapy. Leucoconcentrate obtained from mini pig peripheral blood was transduced with a chimeric adenoviral vector (Ad5/35F) that carried an enhanced green fluorescent protein (EGFP) reporter gene in the plastic blood bag. The day after blood donation, the mini pigs were subjected to moderate SCI and four hours post-surgery they were intravenously autoinfused with gene-modified leucoconcentrate. A week after gene-modified leucoconcentrate therapy, fluorescent microscopy revealed EGFP-expressing leucocytes in spinal cord at the site of contusion injury. In the spleen the groups of EGFP-positive cells located in the lymphoid follicles were observed. In vitro flow cytometry and fluorescent microscopy studies of the gene-modified leucoconcentrate samples also confirmed the production of EGFP by leucocytes. Thus, the efficacy of leucocytes transduction in the plastic blood bag and their migratory potential suggest their use for temporary production of recombinant biologically active molecules to correct certain pathological conditions. This paper presents a proof-of-concept of simple, safe and effective approach for personalized ex vivo gene therapy based on gene-modified leucoconcentrate autoinfusion. The animal protocols were approved by the Kazan State Medical University Animal Care and Use Committee (approval No. 5) on May 27, 2014.

Nowadays gene and cell therapy become the basic methods in regenerative medicine. However only few gene and cell products are currently approved for clinical usage. Biosafety problems, complexity of cell and gene technologies and high cost of manufacturing are the main reasons for the slow introduction of such approaches in practical medicine. Treatment of hereditary diseases of the immune system based on the correction of the mutant gene by delivering functional recombinant gene into WBC is the first successfully employed in the clinical practice approach of cell-mediated or ex vivo gene therapy. Earlier we have reported the strategy of the cell-mediated gene therapy based on umbilical cord blood mononuclear cells transduced with adenoviral vectors carrying recombinant genes encoding neurotrophic factors for treatment neurodegenerative diseases, neurotrauma and stroke. Significant disadvantage of this method is the usage of the umbilical cord blood mononuclear cells as a cell carrier for the therapeutic genes. Considering immunodeficiency treatment and our own data we developed a new approach of recombinant gene delivery for personalized ex vivo gene therapy. The method is based on autoinfusion of patient's WBC transduced with recombinant therapeutic genes for correction of certain pathological conditions. In the present study for the first time the human gene-modified leucoconcentrate (GML) producing recombinant reporter gene encoding green fluorescent protein (GFP) was obtained without culturing WBC in vitro. The routine unit of peripheral blood (450 ml) was collected into the plastic blood bag and the leucocyte- and platelet-rich concentrates (50 ml) were obtained by standard method using Macopress Smart (Macopharma, France). Afterwards the equal volume of hydroxyethyl starch 6% was added into the plastic blood bag which was centrifuged (DP-2065 R PLUS, Centrifugal Presvac RV; Presvac, Buenos Aires, Argentina) at 350 rpm for 10 min at 10°C. The obtained supernatant was transferred into the new plastic blood bag using manual plasma extractor FK-01 (Leadcore, Russia) and 200 ml of saline was added into the bag which was centrifuged at 1300 rpm for 10 min at 10°C and the supernatant was expressed out of the bag so that the remaining solution in the bag (30 ml) contained leucoconcentrate (WBC - 45.56 ± 23.93 × 106/ml and RBC - 1.76 ± 3.33 × 109/ml). Transduction of WBC with chimeric adenoviral vector (Ad5/35) carrying GFP gene was performed in the plastic bag with MOI 5 according to the count of WBC in the leucoconcentrate. After transduction for 12 hours, 200 ml of saline was added to the bag with leucoconcentrate, the mixture was centrifuged at 1000 rpm for 10 min at 10°C and the supernatant was squeezed out of the bag. The remained in the bag solution (30 ml) was considered as gene-modified leucoconcentrate carrying GFP gen (WBC - 22.63 ± 8.90 × 106/ml and RBC - 1.77 ± 1.21 × 109/ml). For in vitro study of GFP gene expression the samples of GML-GFP were cultivated for 60 hours after GML-GFP preparation. Fluorescent microscopy in the cytoplasm of the transduced WBC showed specific intensive green fluorescence. Flow cytometry analysis demonstrated that 2.5% of WBC from the GML-GFP efficiently expressed GFP. Thus leucoconcentrate after 72 h of transduction with Ad5/35-GFP with MOI 5 resulted in 2.5% of the GFP-positive cells. Thus the results of this study represent a simple, safe and effective approach for preparation of GML for personalized ex vivo gene therapy aimed at temporary production of the specific recombinant biologically active molecules for pathogenetic therapy of the varied nosological form, such as trauma, ischemic, degenerative, autoimmune, infection and other diseases. This study was supported by the grant of Russian Science Foundation 19-75-10030. Disclosures No relevant conflicts of interest to declare.

Dual-ion battery (DIB) can potentially provide higher power, lower cost and faster charging capability than traditional lithium-ion batteries. Even though graphite can effectively accommodate anions as a cathode for DIB, the high working voltage of around 5 V vs. Li/Li+ leads to continuous side reactions, yielding to low Coulombic efficiency (CE

Coupling of electric and magnetic responses of a scatterer, known as bianisotropy, enables rich physics and unique optical phenomena, including asymmetric absorption or reflection, one-way transparency, and photonic topological phases. Here we demonstrate yet another feature stemming from bianisotropic response, namely, polarization-dependent scattering of light by bianisotropic dielectric meta-atom with broken mirror symmetry, which yields a photonic analogue of spin Hall effect. Based on a simple dipole model, we explain the origin of the effect confirming our conclusions by experimental observation of photonic spin Hall effect both for a single meta-atom and for an array of them.

Botulism is a potentially fatal intoxication caused by botulinum neurotoxins (BoNTs) produced mainly by Clostridium botulinum. Vaccination against BoNT serotypes C and D is the main procedure to control cattle botulism. Current vaccines contain formaldehyde-inactivated native BoNTs, which have a time-consuming production process and pose safety risks. The development of non-toxic recombinant vaccines has helped to overcome these limitations. This study aims to evaluate the humoral immune response generated by cattle immunized with non-purified recombinant fragments of BoNTs C and D. Cattle were vaccinated in a two-dose scheme with 100, 200 and 400 &micro, g of each antigen, with serum sampling on days 0, 56, 120, and 180 after vaccination. Animals who received either 200 or 400 &mu, g of both antigens induced titers higher than the minimum required by the Brazilian ministry of Agriculture, Livestock and Food Supply and achieved 100% (8/8) seroconversion rate. Animals vaccinated with commercial toxoid vaccine had only a 75% (6/8) seroconversion rate for both toxins. Animals that received doses containing 400 &micro, g of recombinant protein were the only ones to maintain titers above the required level up until day 120 post-vaccination, and to achieve 100% (8/8) seroconversion for both toxins. In conclusion, 400 &micro, g the recombinant Escherichia coli cell lysates supernatant was demonstrated to be an affordable means of producing an effective and safe botulism vaccine for cattle.

BACKGROUND: The prevalence of chronic disease and do-not-intubate status increases with age. Thus, we aimed to determine characteristics and outcomes associated with noninvasive ventilation (NIV) use for acute respiratory failure (ARF) in different age groups. METHODS: A database comprising prospective data collected on site on all adult patients with ARF requiring ventilatory support from 8 acute care hospitals in Massachusetts was used. RESULTS: From a total of 1,225 ventilator starts, overall NIV utilization, success, and in-hospital mortality rates were 22, 54, and 18% in younger (18-44 y); 34, 65, and 13% in middle-aged (45-64 y); 49, 68, and 17% in elderly (65-79 y); and 47, 76, and 24% in aged (>= 80 y) groups, respectively (P < .001, P = .08, and P = .11, respectively). NIV use for cardiogenic pulmonary edema and subjects with a do-not-intubate order increased significantly with advancing age (25, 57, 57, and 74% and 7, 12, 18, and 31%, respectively, in the 4 age groups [P < .001 and P = .046, respectively]). For subjects receiving NIV with a do-not-intubate order, success and in-hospital mortality rates were similar in different age groups (P = .27 and P = .98, respectively). CONCLUSIONS: NIV use and a do-not-intubate status are more frequent in subjects with ARF >= 65 y than in those < 65 y, especially for subjects with cardiogenic pulmonary edema. However, NIV success and mortality rates were similar between age groups.

Purpose The impact of a clinical pharmacist-led medication management program (MMP) within a patient-centered medical home (PCMH) was evaluated. Methods This retrospective analysis included patients in Sutter Health’s electronic health records who (1) were seen by the MMP clinical pharmacist within the PCMH (MMP cohort), (2) were within the PCMH but were not referred to the MMP pharmacist (PCMH cohort), or (3) received usual care at two non-PCMH primary care clinics (usual care cohort). Patients were matched on their propensity for receiving medication management. The primary outcome measure was healthcare resource use (i.e., ambulatory care visits, emergency department [ED] visits, and hospitalizations). Results MMP patients had a higher percentage of ambulatory care visits relative to PCMH patients ( p = 0.004) but a lower rate of hospitalizations ( p = 0.003). The MMP group had a lower frequency of hospitalizations ( p < 0.001) and ED visits ( p = 0.014) relative to patients in the usual care group. No differences in healthcare resource use were observed between the PCMH and usual care cohorts. Glycosylated hemoglobin, blood pressure, or low-density-lipoprotein cholesterol at goal did not significantly differ among the three cohorts. Conclusion Patients in a pharmacist-led MMP had a significantly higher estimated rate of ambulatory care visits but a lower rate of hospitalizations than did patients who attended the same clinic but were not in the MMP. MMP patients had a similar rate of ambulatory care visits but significantly lower rates of hospitalizations and ED visits than patients receiving usual care.

This article contains information about creating special unit for scanning 3D objects. The main part of the unit is ultrasonic transducer, which is sends the sound wave to the object and receive back wave for calculating distance. After that, microcontroller send to PC data, and computer program create model for printing from the plastic etc.

The modern development of regional socio-economic systems and their stable functioning largely depend on the quality of human resources, expressed in the level of development, generation and application of new knowledge. It is these resources in the innovation economy that have a priority character and are the dominant factors of the reproductive and economic processes. In this connection, the article provides a comprehensive assessment of the use of regional human resources. During the research, the most significant factors that determine the development of the personnel potential of the territories are identified, which are grouped into groups of infrastructural, social and economic conditions. The work uses official Russian statistics for a long time interval and normalizes the initial values to ensure comparability of the data. The author’s methodology also assumes the calculation of integral indicators by calculating the average geometric by groups of infrastructural, social and economic indicators. Methods of statistical and logical analysis, comparisons, tabular representation of data were used in the work. Also, to substantiate the author’s conclusions, three-dimensional graphic models have been constructed that demonstrate and allow us to assess the real positions of the subjects of the Central Federal District of the Russian Federation in the space of the analyzed factors.

The gene therapy has been successful in treatment of spinal cord injury (SCI) in several animal models, although it still remains unavailable for clinical practice. Surprisingly, regardless the fact that multiple reports showed motor recovery with gene therapy, little is known about molecular and cellular changes in the post-traumatic spinal cord following viral vector- or cell-mediated gene therapy. In this study we evaluated the therapeutic efficacy and changes in spinal cord after treatment with the genes encoding vascular endothelial growth factor (VEGF), glial cell-derived neurotrophic factor (GDNF), angiogenin (ANG), and neuronal cell adhesion molecule (NCAM) applied using both approaches. Therapeutic genes were used for viral vector- and cell-mediated gene therapy in two combinations: (1) VEGF+GDNF+NCAM and (2) VEGF+ANG+NCAM. For direct gene therapy adenoviral vectors based on serotype 5 (Ad5) were injected intrathecally and for cell-mediated gene delivery human umbilical cord blood mononuclear cells (UCB-MC) were simultaneously transduced with three Ad5 vectors and injected intrathecally 4 h after the SCI. The efficacy of both treatments was confirmed by improvement in behavioral (BBB) test. Molecular and cellular changes following post-traumatic recovery were evaluated with immunofluorescent staining using antibodies against the functional markers of motorneurons (Hsp27, synaptophysin, PSD95), astrocytes (GFAP, vimentin), oligodendrocytes (Olig2, NG2, Cx47) and microglial cells (Iba1). Our results suggest that both approaches with intrathecal delivery of therapeutic genes may support functional recovery of post-traumatic spinal cord via lowering the stress (down regulation of Hsp25) and enhancing the synaptic plasticity (up regulation of PSD95 and synaptophysin), supporting oligodendrocyte proliferation (up regulation of NG2) and myelination (up regulation of Olig2 and Cx47), modulating astrogliosis by reducing number of astrocytes (down regulation of GFAP and vimetin) and microglial cells (down regulation of Iba1).

Background This study determined actual utilization rates and outcomes of noninvasive positive pressure ventilation (NIV) at selected hospitals that had participated in a prior survey on NIV use. Methods This observational cohort study, based at eight acute care hospitals in Massachusetts, focused on all adult patients requiring ventilatory support for acute respiratory failure during predetermined time intervals. Results Of 548 ventilator starts, 337 (61.5%) were for invasive mechanical ventilation and 211 (38.5%) were for NIV, with an overall NIV success rate of 73.9% (ie, avoidance of intubation or death while on NIV or within 48 h of discontinuation). Causal diagnoses for respiratory failure were classified as (I) acute-on-chronic lung disease (23.5%), (II) acute de novo respiratory failure (17.9%), (III) neurologic disorders (19%), (IV) cardiogenic pulmonary edema (16.8%), (V) cardiopulmonary arrest (12.2%), and (VI) others (10.6%). NIV use and success rates for each of the causal diagnoses were, respectively, (I) 76.7% and 75.8%, (II) 37.8% and 62.2%, (III) 1.9% and 100%, (IV) 68.5% and 79.4%, (V) none, and (VI) 17.2% and 60%. Hospital mortality rate was higher in patients with invasive mechanical ventilation than in patients with NIV (30.3% vs 16.6%, P Conclusions NIV occupies an important role in the management of acute respiratory failure in acute care hospitals in selected US hospitals and is being used for a large majority of patients with acute-on-chronic respiratory failure and acute cardiogenic pulmonary edema. NIV use appears to have increased substantially in selected US hospitals over the past decade. Trial registry ClinicalTrials.gov; No.: NCT00458926; URL: www.clinicaltrials.gov

To examine outcomes associated with colesevelam treatment among patients with hypercholesterolemia in real-world clinical practice.This analysis was conducted as a retrospective, observational cohort study in an ambulatory-care medical network in Northern California. Patients with orders for colesevelam were identified in the electronic health record between January 2004 and December 2011. The date of the first order during the study period was designated the index date. Patients were evaluated for the following eligibility criteria: a diagnosis of hypercholesterolemia, ≥18 years of age at index date, baseline laboratory values ≤3 months before the index date, ≥12 months of treatment and follow-up, and no prior orders for colesevelam ≤12 months before the index date. Patients who were pregnant during the study period were excluded. Changes in LDL-C and percentage of patients at LDL-C goal were examined. Among patients with diabetes mellitus (DM), changes in glycated hemoglobin (HBA1C) and percentage of patients at HBA1C goal were also examined.Overall, 468 and 181 patients with hypercholesterolemia met the predefined inclusion criteria with treatment and follow-up through 12 and 24 months, respectively. LDL-C decreased significantly from baseline by a mean of 11.4 mg/dL and 15.7 mg/dL (P0.0001, for each) at 12 and 24 months, respectively, and the percentages of patients at LDL-C goal increased by 13.9% and 21.0%. Among patients with DM and a baseline HBA1C ≥8%, 113 and 39 had treatment and follow-up through 12 and 24 months, respectively. HBA1C decreased significantly by a mean of 0.72% (P = 0.0001) and 0.75% (P = 0.010) and 11.5% and 12.8% were at HBA1C goal at 12 and 24 months, respectively. This study is limited by its retrospective and observational study design.Colesevelam treatment in a real-world setting was associated with improvements in LDL-C and HBA1C through 24 months of follow-up.

Background: Postmenopausal osteoporosis (PMO) is associated with substantial morbidity and mortality. Despite established guidelines for the care of PMO, the treatment and management of this disease remain suboptimal. Objective: To examine the treatment and management of PMO in a community-based ambulatory care setting. Methods: Women with a new diagnosis of PMO (International Classification of Diseases, 9th Revision, code 733.01) were identified through the electronic health records (EHR) of a community-based ambulatory care network in northern California between January 1, 2007, and December 31, 2008. Patients were included if they were 65 years of age or older and had EHR activity 26 months or more after diagnosis. They were excluded if they had a diagnosis of osteoporosis (ICD-9:733.xx) prior to the study period. A retrospective review of the EHR and medical charts was performed to identify patients who were prescribed FDA-approved pharmacotherapy, who received bone mineral density (BMD) testing via dual-energy X-ray absorptiometry (DXA), and who experienced a fracture. Results: One hundred thirty-one PMO patients were identified who met study eligibility criteria. Fifty-nine patients (45%) were prescribed FDA-approved pharmacotherapy at diagnosis. Ninety patients (69%) were prescribed pharmacotherapy at any point during follow-up. Sixty-four patients (49%) had a baseline DXA scan and 95 patients (73%) had 1 or more DXA scans during follow-up. Seventeen of 90 patients (19%) who received pharmacotherapy had 2 DXA scans within 2 years of follow-up. Nineteen fractures were reported among 16 patients during the study period. Conclusions: The proportion of patients with PMO who received pharmacologic treatment at diagnosis and had a baseline DXA scan was relatively low; however, the majority of these patients received treatment and had 1 or more DXA scans at some point during the 26-month follow-up period. Future studies should be conducted to assess the role of early BMD testing and pharmacologic intervention in optimizing outcomes among women with PMO.

Despite the availability of effective antihypertensive therapies, adherence to and persistence with treatment is suboptimal. As such, there is a need to better understand factors associated with adherence and persistence, such as race/ethnicity. In a retrospective, exploratory analysis of 51,772 hypertensive adult subjects identified in the electronic medical record, we examined medication possession ratio and proportion of days covered as proxies for adherence and persistence, respectively. Logistic regression analyses were performed to assess the role of race/ethnicity in adherence to and persistence with antihypertensive treatments. Relative to white subjects, Asian American/Pacific Islander, black, Hispanic, and "other" subjects were significantly less likely to be adherent to and persistent with their antihypertensive regimens. Black and Hispanic subjects had the lowest odds of adherence (0.46, 95% CI: 0.43-0.49 and 0.58, 95% CI: 0.54-0.62, respectively) and persistence (0.70, 95% CI: 0.65-0.75 and 0.70, 95% CI: 0.66-0.74, respectively) relative to white subjects. Other factors significantly associated with both lower adherence and persistence included younger age and lower chronic disease score. Disparities were found with regard to adherence to and persistence with antihypertensive regimens. Future studies should address these disparities by designing interventions to improve medication-taking behavior in high-risk populations.

Background: Despite treatment for hypertension, blood pressure (BP) remains uncontrolled in many individuals. Identification of patterns in BP control may inform strategies to improve treatment and optimize health outcomes. Objective: To examine patterns in BP control among individuals receiving antihypertensive treatment in a diverse, community-based provider network. Methods: In this retrospective exploratory analysis, a total of 51.772 hypertensive subjects were identified in the electronic medical record between January 1, 2007, and June 30, 2010, who were aged 18 years or older, with 2 or more claims for antihypertensive medication, documented race/ethnicity, and 1 or more documented BP readings. Results: On the basis of Joint National Committee VII guidelines, 76.4% of nondiabetic patients had their BP controlled with treatment (Conclusions: Potential disparities, particularly among diabetic individuals and those of minority race/ethnicity, were found with regard to BP control and the agents used to treat hypertension. Future studies should address these disparities by designing interventions to improve the treatment of hypertension in high-risk populations.

The increased cardiovascular risk associated with hypertriglyceridemia is thought to be due in part to high levels of triglyceride (TG)-rich lipoproteins and small dense low-density lipoprotein (LDL). In this post hoc analysis, effects of increasing doses of atorvastatin (10, 20, 40, and 80 mg) on atherogenic lipid subclasses commonly associated with hypertriglyceridemia were evaluated in 191 men and women who were candidates for lipid-lowering therapy and had baseline TG levels >200 mg/dl (2.3 mmol/L). After 8 weeks of treatment, in addition to significantly decreasing LDL cholesterol and TG levels, atorvastatin significantly increased LDL peak particle diameter (p

We demonstrate high-efficiency, low-voltage phosphorescent OLED devices (PHOLEDs) using mixed host materials in the light-emitting layer (LEL) and novel formulations in the electrontransporting/ electron-injecting layers (ETL/EIL). The LEL architecture offers significant improvement in efficiency and voltage compared to conventional phosphorescent OLEDs with carbazole-based hosts. Further voltage reduction in our PHOLEDs is achieved through use of a novel material formulation in the ETL and EIL.

Aggregating PAHs of the perylene class are useful as LEL additives. They greatly improve the device operating half-life up to 1,000,000 h at the initial luminance of 1540 cd/m2 (20 mA/cm2). There appear to be at least three factors in the lifetime increase: takeover of the LEL functions by the PAHs, aggregation, and an expansion of the recombination and/or emission zone.

Studies of delayed electroluminescence in highly efficient fluorescent organic light-emitting diodes (OLEDs) of many dissimilar architectures indicate that the triplet–triplet annihilation (TTA) significantly increases yield of excited singlet states—emitting molecules in this type of device thereby contributes substantially to their efficiency. Towards the end of the 2000s, the essential role of TTA in realizing highly efficient fluorescent devices was widely recognized. Analysis of a diverse set of fluorescent OLEDs shows that high efficiencies are often cor-related to TTA extents. It is therefore likely that it is the long-term empirical optimization of OLED efficiencies that has resulted in fortuitous emergence of TTA as a large and ubiquitous contributor to efficiency. TTA contributions as high as 20–30% are common in the state-of-the-art OLEDs, and even become dominant in special cases, where TTA is shown to substantially exceed the spin-statistical limit. The fundamental features of OLED efficiency enhancement via TTA—molecular structure-dependent contributions, current density-dependent intensities in practical devices and frequently observed antagonistic relationships between TTA extent and OLED lifetime—came to be understood over the course of the next few years. More recently, however, there was much less reported progress with respect to all-important quantitative details of the TTA mechanism. It should be emphasized that, to this day and despite the decades of work on improving blue phosphorescent OLEDs as well as the recent advent of thermally activated delayed fluorescence OLEDs, the majority of practical blue OLEDs still rely on TTA. Considering such practical importance of fluorescent blue OLEDs, the design of blue OLED-compatible materials capable of substantially exceeding the spin-statistical limit in TTA, elimination of the antagonistic relationship between TTA-related efficiency gains and lifetime losses, and designing devices with an extended range of current densities producing near-maximum TTA electroluminescence are the areas where future improvements would be most beneficial.

Organic light-emitting diodes (OLEDs) are attractive for display applications because of their high brightness, low driving voltage, and tunable color. Their operating lifetimes, hundreds or thousands of hours, are sufficient for only a limited range of applications. The luminance efficiency decreases gradually as the device is operated (electrically aged), for reasons that are poorly understood. A prototypical OLED has the structure anode|HTL|ETL|cathode, where the HTL and ETL are hole- and electron-transporting layers, and the recombination and emission occur at or near the HTL|ETL interface. We find that the decreasing luminance efficiency is linearly correlated with an accumulation of immobile positive charge at the HTL|ETL interface, and the magnitude of the charge is comparable to the total charge at that interface when an unaged device is operated. A natural explanation of the connection between the two phenomena is that electrical aging either generates hole traps (and trapped holes) or drives met...

Few studies have examined locations of noninvasive ventilation (NIV) application for acute respiratory failure (ARF). We aimed to track actual locations of NIV delivery and related outcomes.Observational cohort study based at 8 acute care hospitals in Massachusetts on adult patients admitted for ARF requiring ventilatory support during pre-determined time intervals.Of 1225 ventilator starts, 499 were NIV; 209 (42%) in intensive care units (ICU), 185 (37%) in emergency departments (ED), 91 (18%) on general wards, and 14 (3%) in other units. Utilization (% of all ventilator starts) (1), success (2) and in-hospital mortality (3) rates for patients initiated on NIV in ICU, ED, and general and other wards were (1) 38, 36, 73, and 52%, (2) 60, 77, 68, and 93% and (3) 25, 12, 17, and 0%, respectively (p0.05 for all). Patients with acute-on-chronic lung disease (ACLD) and acute pulmonary edema (APE) were begun on NIV most often in EDs and patients with 'de novo' ARF and neurologic disorders most often in ICU's. Approximately 2/3 of patients begun on NIV outside of ICUs were transferred within 72 h to ICUs, wards or other units.Most NIV starts occurred in ICUs and EDs but utilization rate was highest (50%) on general wards where a fifth of NIV starts took place. Actual location depended on etiology of ARF as patients with ACLD and APE were started more often in EDs and "de novo" ARF in ICU. NIV failure and mortality rates were higher in ICUs related to the greater proportion of patients with "de novo" ARF.