Metal Organic Frameworks as Promising High Surface Area Material for Work Function Gas Sensors

AbstractFloating gate FET (FGFET) gas sensors based on work function readout allows usage of a wide range of materials to be included as sensing materials. Metal-organic frameworks (MOFs) are a new group of porous materials with extreme high inner surface area that have already shown high potential for applications in gas storage and separation, catalysis and sensing. In this work, MOFs are investigated for the first time with work function readout for gas sensing applications. The results demonstrate the high potential of MOFs for use as gas receptor materials in field- effect based gas sensors

COVID-19 Outcomes and Vaccination in People with Relapsing Multiple Sclerosis Treated with Ofatumumab

COVID-19; Ofatumumab; VaccinationCOVID-19; Ofatumumab; VacunaciónCOVID-19; Ofatumumab; VacunacióIntroduction The SARS-CoV-2 pandemic necessitated better understanding of the impact of disease-modifying therapies on COVID-19 outcomes and vaccination. We report characteristics of COVID-19 cases and vaccination status in ofatumumab-treated relapsing multiple sclerosis (RMS) patients. Methods COVID-19 data analyzed were from the ongoing, open-label, long-term extension phase 3b ALITHIOS study from December 2019 (pandemic start) and post-marketing cases from August 2020 (ofatumumab first approval) up to 25 September 2021. COVID-19 cases, severity, seriousness, outcomes, vaccination status, and breakthrough infection were evaluated. Results As of 25 September 2021, 245 of 1703 patients (14.4%) enrolled in ALITHIOS receiving ofatumumab (median exposure: 2.45 years) reported COVID-19 (confirmed: 210; suspected: 35). Most COVID-19 was of mild (44.1%) or moderate (46.5%) severity, but 9% had severe/life-threatening COVID-19. There were 24 serious cases (9.8%) with 23 patients hospitalized; 22 recovered and 2 died. At study cut-off, 241 patients (98.4%) had recovered or were recovering or had recovered with sequelae and 2 (0.8%) had not recovered. Ofatumumab was temporarily interrupted in 39 (15.9%) patients. Before COVID-19 onset, IgG levels were within the normal range in all COVID-19–affected patients, while IgM was < 0.4 g/l in 23 (9.4%) patients. No patient had a reinfection. Overall, 559 patients were vaccinated (full, 476; partial, 74; unspecified, 9). Breakthrough infection was reported in 1.5% (7/476) patients, and 11 reported COVID-19 after partial vaccination. As of 25 September 2021, the Novartis Safety Database (~ 4713 patient-treatment years) recorded 90 confirmed COVID-19 cases receiving ofatumumab. Most cases were non-serious (n = 80), and ten were serious (1 medically significant, 9 hospitalized, 0 deaths). Among 36 of 90 cases with outcomes reported, 30 recovered and 6 did not recover. Conclusion COVID-19 in RMS patients on ofatumumab was primarily of mild/moderate severity and non-serious in these observational data. Most recovered from COVID-19 without treatment interruption. Two people died with COVID-19. Breakthrough COVID-19 despite being fully/partially vaccinated was uncommon.The study sponsor (Novartis Pharma AG, Basel, Switzerland) participated in the design and conduct of the study, data collection, data management, data analysis and data interpretation; preparation, review, and approval of the manuscript, as well as writing of the report and decision to submit the paper for publication. All authors had full access to all study data and took final responsibility for the decision to submit the manuscript for publication. The journal rapid service fee for this publication was funded by Novartis Pharma AG, Basel, Switzerland

Rapid and sustained B-cell depletion with subcutaneous ofatumumab in relapsing multiple sclerosis: APLIOS, a randomized phase-2 study

Ofatumumab; Multiple sclerosis; PharmacokineticsOfatumumab; Esclerosis múltiple; FarmacocinéticaOfatumumab; Esclerosi múltiple; FarmacocinèticaBackground: Ofatumumab, the first fully human anti-CD20 monoclonal antibody, is approved in several countries for relapsing multiple sclerosis (RMS). Objective: To demonstrate the bioequivalence of ofatumumab administered by an autoinjector versus a pre-filled syringe (PFS) and to explore the effect of ofatumumab on B-cell depletion. Methods: APLIOS (NCT03560739) is a 12-week, open-label, parallel-group, phase-2 study in patients with RMS receiving subcutaneous ofatumumab 20 mg every 4 weeks (q4w) (from Week 4, after initial doses on Days 1, 7, and 14). Patients were randomized 10:10:1:1 to autoinjector or PFS in the abdomen, or autoinjector or PFS in the thigh, respectively. Bioequivalence was determined by area under the curve (AUCτ) and maximum plasma concentration (Cmax) for Weeks 8–12. B-cell depletion and safety/tolerability were assessed. Results: A total of 256 patients contributed to the bioequivalence analyses (autoinjector-abdomen, n = 128; PFS-abdomen, n = 128). Abdominal ofatumumab pharmacokinetic exposure was bioequivalent for autoinjector and PFS (geometric mean AUCτ, 487.7 vs 474.1 h × µg/mL (ratio 1.03); Cmax, 1.409 vs 1.409 µg/mL (ratio 1.00)). B-cell counts (median cells/µL) depleted rapidly in all groups from 214.0 (baseline) to 2.0 (Day 14). Ofatumumab was well tolerated. Conclusion: Ofatumumab 20 mg q4w self-administered subcutaneously via autoinjector is bioequivalent to PFS administration and provides rapid B-cell depletion.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: the APLIOS trial was funded by Novartis Pharmaceuticals. Novartis Pharmaceuticals supported the development of this manuscript, provided data analyses according to the direction of the authors, and paid for medical writing support

Electrical detection of hyperbolic phonon-polaritons in heterostructures of graphene and boron nitride

Light properties in the mid-infrared can be controlled at a deep subwavelength scale using hyperbolic phonons-polaritons (HPPs) of hexagonal boron nitride (h-BN). While propagating as waveguided modes HPPs can concentrate the electric field in a chosen nano-volume. Such a behavior is at the heart of many applications including subdiffraction imaging and sensing. Here, we employ HPPs in heterostructures of h-BN and graphene as new nano-optoelectronic platform by uniting the benefits of efficient hot-carrier photoconversion in graphene and the hyperbolic nature of h-BN. We demonstrate electrical detection of HPPs by guiding them towards a graphene pn-junction. We shine a laser beam onto a gap in metal gates underneath the heterostructure, where the light is converted into HPPs. The HPPs then propagate as confined rays heating up the graphene leading to a strong photocurrent. This concept is exploited to boost the external responsivity of mid-infrared photodetectors, overcoming the limitation of graphene pn-junction detectors due to their small active area and weak absorption. Moreover this type of detector exhibits tunable frequency selectivity due to the HPPs, which combined with its high responsivity paves the way for efficient high-resolution mid-infrared imaging

Dissociation of two-dimensional excitons in monolayer WSe₂

In two-dimensional semiconductors excitons are strongly bound, suppressing the creation of free carriers. Here, the authors investigate the main exciton dissociation pathway in p-n junctions of monolayer WSe2 by means of time and spectrally resolved photocurrent measurements

The Influence of Cu\u3csub\u3e3\u3c/sub\u3e(BTC)\u3csub\u3e2\u3c/sub\u3e metal organic framework on the permeability and perm-selectivity of PLLA-MOF mixed matrix membranes

Poly(l-lactic acid) (PLLA) - 20% (w/w) and Cu3(BTC)2 metal organic framework (MOF) based mixed matrix membranes (MMMs) were fabricated by a vertical corotating twin screw microcompounder followed by an injection molding process. Water vapor, CO2, O2, and selected aroma mass transfer properties of PLLA and PLLA MMMs were evaluated. The CO2/O2 perm-selectivity of PLLA (αCO2/O2) MMMs increased from 7.6 to 10.3 with the incorporation of 20% Cu3(BTC)2 MOF. Gravimetric permeability studies of trans-2-hexenal performed at 23°C and 50% RH indicated that permeability coefficient of PLLA MMMs increased by around 60% as compared to regular PLLA film. However, no changes in mass transfer rates were observed for acetaldehyde. Furthermore, the thermal processing parameters as well as the presence of MOF did not show any significant effect on the molecular weight of the PLLA matrix nor on the crystalline structure of the Cu3(BTC)2 MOF, which was confirmed by both gel permeation chromatography and X-ray diffraction studies

Методика проведения клинико-экономических исследований лекарственных препаратов для лечения злокачественных новообразований с применением моделирования

The aim is to develop a generalized algorithm and methodology for conducting clinical and economic studies (CeS) on medications used in treatment of malignant neoplasms (MnP). Materials and methods. We conducted a literature search and then reviewed the recent reports on similar CeS. In so doing, we paid special attention to the model type, the modeling methodology, information on the effectiveness and cost, the cost elements, performance criteria, the assessment of the CeS final results, as well as the possibility of applying these results to the national healthcare system. We used the methods of generalization, systematization, as well as visual-graphical and mathematical modeling. Results. A general algorithm for conducting a pharmacoeconomic study has been proposed; this includes an effectiveness analysis, a cost analysis and a comparison of costs and effectiveness (cost-effectiveness). The effectiveness analysis includes selection, digitization, and approximation of overall survival (OS) and progression-free survival (PFS) curves followed by their extrapolation. The choice of extrapolation method is discussed. The cost analysis includes calculating the cost of medications in question, the costs associated with the indicated therapy and with adverse events (Ae), as well the costs associated with disease progression (for certain drugs). The possibility of analyzing indirect and non-medical costs is also discussed. A dynamic version of the Markov model pertaining to the first order course of a disease is proposed; this includes the status before progression (first-line therapy), after progression (second-line therapy) and death. Considering the succession of treatments and the availability of additional data, a similar second-order model (and subsequent orders) can be applied to incorporate additional patient’s condition after the first progression to the second progression (second-line therapy) and after the second progression (third-line therapy). Conclusion. A generalized algorithm has been developed and proposed for carrying out CeS of medications used in MnP.Цель – поиск и описание обобщенного алгоритма и методики проведения клинико-экономических исследований (КЭИ) лекарственных препаратов, применяемых при злокачественных новообразованиях (ЗНО). Материалы и методы. Для разработки обобщенного алгоритма проведения КЭИ лекарственных препаратов, применяемых в онкологии, мы провели литературный поиск и анализ подобных КЭИ, опубликованных за последнее время. При рассмотрении отдельных КЭИ обращали внимание на вид модели, детали методики моделирования, источники информации об эффективности и стоимости, виды затрат, критерии эффективности, единицы измерения конечных результатов КЭИ, а также возможность применения результатов в реальных условиях функционирования отечественной системы здравоохранения. Использовали методы обобщения, систематизации, моделирования, визуально-графические и математические. Результаты. Предложен общий алгоритм проведения фармакоэкономического исследования, который включает анализ эффективности, анализ затрат и сопоставление затрат и эффективности (затраты-эффективность). Анализ эффективности включает выбор, оцифровку и аппроксимацию кривых общей выживаемости (ОВ) и выживаемости без прогрессирования (ВБП) с дальнейшей экстраполяцией. Обсуждается выбор метода экстраполяции. Анализ затрат включает расчет стоимости рассматриваемых лекарственных препаратов, затрат, связанных с их использованием, в том числе затрат на лечение нежелательных явлений (НЯ), а также определение затрат в состоянии прогрессирования (на определенные лекарственные препараты). Также обсуждается возможность анализа непрямых и немедицинских затрат. Предложена динамическая Марковская модель течения ЗНО первого порядка, включающая состояния до прогрессирования (первая линия терапии), после прогрессирования (вторая линия терапии) и смерть. При рассмотрении последовательностей линий терапии и наличии дополнительных данных может быть использована аналогичная модель второго порядка (и последующих порядков), включающая дополнительно состояние после первого прогрессирования до второго прогрессирования (вторая линия терапии) и после второго прогрессирования (третья линия терапии). Заключение. Разработан и описан обобщенный алгоритм проведения КЭИ лекарственных препаратов, применяемых при ЗНО, и т.д

Ocrelizumab in treatment of primary-progressive multiple sclerosis: systematic review

Aim. To analyze the efficacy, safety and pharmacoeconomic indicators of ocrelizumab in adult patients with primary progressive multiple sclerosis (PPMS). Methods. An information search was conducted in the databases Embase, PubMed, Cochrane and eLibrary.ru. The levels of evidence were determined in the studies. Results. Therapy with ocrelizumab compared with placebo characterized by a decrease in the rate of progression of the disease. Treatment with ocrelizumab was associated with a significant slowdown in progression compared to other drugs: rituximab, fingolimod, myelin basic protein peptide 82–98, intravenous immunoglobulin; plasmapheresis / plasma metabolism, corticosteroids, general irradiation of lymphoid tissue, and other most common adverse events: infusion reactions, nasopharyngitis, upper tract respiratory and urinary tract infections, headaches. Life years and quality-adjusted life years for patients receiving ocrelizumab were 16.11 and 3.33, compared with 15.61 and 2.75 for patients receiving better supportive care, respectively. The annual average potential impact on the budget for 1 patient with PPMS in the treatment of ocrelizumab for 5 years ranged from $ 18,300 to 44 200. Conclusions. Ocrelizumab is the only drug that has proven its clinical efficacy in the previously non-curable type of multiple sclerosis, PPC, with risk profile acceptable with respect to clinical benefits

Rapid and sustained B-cell depletion with subcutaneous ofatumumab in relapsing multiple sclerosis : APLIOS, a randomized phase-2 study

Background: Ofatumumab, the first fully human anti-CD20 monoclonal antibody, is approved in several countries for relapsing multiple sclerosis (RMS). Objective: To demonstrate the bioequivalence of ofatumumab administered by an autoinjector versus a pre-filled syringe (PFS) and to explore the effect of ofatumumab on B-cell depletion. Methods: APLIOS (NCT03560739) is a 12-week, open-label, parallel-group, phase-2 study in patients with RMS receiving subcutaneous ofatumumab 20 mg every 4 weeks (q4w) (from Week 4, after initial doses on Days 1, 7, and 14). Patients were randomized 10:10:1:1 to autoinjector or PFS in the abdomen, or autoinjector or PFS in the thigh, respectively. Bioequivalence was determined by area under the curve (AUCτ) and maximum plasma concentration (Cmax) for Weeks 8-12. B-cell depletion and safety/tolerability were assessed. Results: A total of 256 patients contributed to the bioequivalence analyses (autoinjector-abdomen, n = 128; PFS-abdomen, n = 128). Abdominal ofatumumab pharmacokinetic exposure was bioequivalent for autoinjector and PFS (geometric mean AUCτ, 487.7 vs 474.1 h × µg/mL (ratio 1.03); Cmax, 1.409 vs 1.409 µg/mL (ratio 1.00)). B-cell counts (median cells/µL) depleted rapidly in all groups from 214.0 (baseline) to 2.0 (Day 14). Ofatumumab was well tolerated. Conclusion: Ofatumumab 20 mg q4w self-administered subcutaneously via autoinjector is bioequivalent to PFS administration and provides rapid B-cell depletion

ТАРГЕТНЫЙ ПРЕПАРАТ БРЕНТУКСИМАБ ВЕДОТИН ДЛЯ ЛЕЧЕНИЯ РЕЦИДИВИРУЮЩЕЙ ИЛИ РЕФРАКТЕРНОЙ CD30-ПОЛОЖИТЕЛЬНОЙ ЛИМФОМЫ ХОДЖКИНА

Objective. To perform literature review of clinical trials reporting on the use of single-agent brentuximab vedotin (BV) 1.8 mg/kg therapy in adult patients with relapsed/refractory (R/R) CD30-positive Hodgkin lymphoma (HL).Methods. A literature search was performed in Pubmed and eLIBRARY. RU databases to identify all studies published from 1 July 2007 until 1 July 2017. We used the key words “brentuximab vedotin” and “Hodgkin lymphoma” simultaneously. The inclusion criteria required that study population included ≥ 20 adult patients with R/R HL. We included clinical trials, systematic reviews, meta-analysis, pharmacoeconomic studies: total 25 publications met inclusion criteria. Publications were grouped by 3 BV indications in instruction for use: adult patient with relapsed/refractory CD30-positive Hodgkin lymphoma post-autologous stem cell transplantation (postASCT), adult patient with refractory CD30-positive HL after failure of at least 2 prior multiagent chemotherapy regimens in patients who are not candidates for ASCT, adult patient with classical HL at high risk of relapse or progression post-ASCT.Results. Overall response rate (ORR) and complete rate (CR) were 75% and 34% respectively in adult patients with R/R CD30-positive HL post-ASCT in SGN35–0003 study. In patients with refractory HL after failure of at least 2 prior multiagent chemotherapy regimens who are not candidates for auto-SCT ORR and CR were 40% and 30% respectively. In mixed population ORR were 56-80%, CR – 10-46.5%. In patients with CD30-positive Hodgkin lymphoma at increased risk of relapse or progression following ASCT ORR was not evaluated, median progression-free survival was improved in patients in BV group compared with those in placebo group (42.9 and 24.1 months respectively). Overall survival in both group was similar. In patients with R/R CD30-positive HL the incremental cost-effectiveness ratio per quality-adjusted life year (ICER/QALY) was 6.7 million rub. и 3 million rub. from a Russian and a Scottish healthcare payer respectively. ICER/QALY when BV compared with best supportive care was 9.79 million rubles. In patients who were at risk for HL repapse after ASCT if BV consolidation compared with active surveillance ICER/QALY was 8.86 million rub.Conclusion. As a result of the literature review, it was found that the response rate, the complete response to BV therapy, and the overall survival and progression-free survival with use of BV in different patient populations differ; in most cases, the result of effectiveness favors BV. The found safety data indicated a good tolerability of the drug. The results of the found pharmacoeconomic studies differ depending on the comparison therapy and the accepted pharmacoeconomic indicator.Цель исследования. Обзор основных опубликованных за последние 10 лет клинических исследований эффективности брентуксимаба ведотина (БВ) в рекомендуемой дозе 1,8 мг/кг у взрослых пациентов с рецидивирующей или рефрактерной (р/р) СD30-положительной лимфомой Ходжкина (ЛХ).Материалы и методы. Поиск литературы был проведен в базах данных Pubmed и eLIBRARY.RU с временным фильтром (2007–2017 гг.) по ключевым словам «брентуксимаб ведотин» (brentuximab vedotin), «лимфома Ходжкина» (Hodgkin lymphoma) одновременно. Были включены рандомизированные и нерандомизированные клинические исследования (КИ), систематические обзоры и мета-анализы и фармакоэкономические исследования, в которых было ≥ 20 взрослых пациентов с р/р ЛХ, получавших БВ в дозе 1,8 мг/кг. Данные из 25 отобранных публикаций были сгруппированы в соответствии с тремя популяциями пациентов с ЛХ из инструкции по применению препарата.Результаты. В исследовании SGN35–0003 у пациентов с р/р ЛХ после аутологичной трансплантации гемопоэтических стволовых клеток (аутоТГСК) частота ответа и полного ответа составили 75% и 34% соответственно. В другом исследовании у пациентов с рефрактерной ЛХ после как минимум двух линий предшествующей терапии, когда аутоТГСК или комбинированная терапия не рассматривается как вариант лечения, частота ответа и полного ответа составила 40% и 30% соответственно. В исследовании смешанной популяции пациентов частота ответа составила от 56 до 80%, а частота полного ответа – от 10 до 46,5%. В исследовании AETHERA у пациентов с повышенным риском рецидива после аутоТГСК частота ответа не оценивалась, медиана выживаемости без прогрессии (ВБП) составила 42,9 мес. и 24,1 мес. в группе БВ и плацебо соответственно. Выживаемость в группе БВ и плацебо оказалась схожей. В двух найденных фармакоэкономических исследованиях было обнаружено, что для пациентов с р/р ЛХ после аутоТГСК показатель приращения эффективности затрат за дополнительный год жизни с поправкой на качество (ICER/QALY) для БВ по сравнению ХТ±ЛТ составил 6,7 млн рублей и 3 млн рублей с точки зрения российского и шотландского плательщика соответственно. Показатель ICER/LY для БВ – ниже по сравнению с ХТ±ЛТ+аллоТСК на 0,6 млн руб. для российского плательщика. В другом исследовании ICER/QALY при сравнении терапии БВ с поддерживающей терапией составил 9,79 млн руб. В четвертой публикации у пациентов с риском рецидива после аутоТГСК было проведено сравнение консолидационной терапии БВ и активного наблюдения, ICER/QALY составил 8,86 млн руб.Выводы. В итоге проведенного литературного обзора обнаружено, что частота ответа, полного ответа на терапию БВ, а также общая выживаемость и выживаемость без прогрессии при применении БВ у разных популяций пациентов отличаются; в большинстве случаев отмечен результат эффективности в пользу БВ. В найденных данных по безопасности отмечена хорошая переносимость препарата. Результаты найденных фармакоэкономических исследований отличаются в зависимости от терапии сравнения и принятого фармакоэкономического показателя