Model study of adsorbed metallic quantum dots: Na on Cu(111)

We model electronic properties of the second monolayer Na adatom islands (quantum dots) on the Cu(111) surface covered homogeneously by the first Na monolayer. An axially-symmetric three-dimensional jellium model, taking into account the effects due to the first Na monolayer and the Cu substrate, has been developed. The electronic structure is solved within the local-density approximation of the density-functional theory using a real-space multigrid method. The model enables the study of systems consisting of thousands of Na-atoms. The results for the local density of states are compared with differential conductance ($dI/dV$) spectra and constant current topographs from Scanning Tunneling Microscopy.Comment: 10 pages, 8 figures. For better quality figures, download http://www.fyslab.hut.fi/~tto/cylart1.pd

A patient-derived xenograft pre-clinical trial reveals treatment responses and a resistance mechanism to karonudib in metastatic melanoma

Karonudib (TH1579) is a novel compound that exerts anti-tumor activities and has recently entered phase I clinical testing. The aim of this study was to conduct a pre-clinical trial in patient-derived xenografts to identify the possible biomarkers of response or resistance that could guide inclusion of patients suffering from metastatic melanoma in phase II clinical trials. Patient-derived xenografts from 31 melanoma patients with metastatic disease were treated with karonudib or a vehicle for 18 days. Treatment responses were followed by measuring tumor sizes, and the models were categorized in the response groups. Tumors were harvested and processed for RNA sequencing and protein analysis. To investigate the effect of karonudib on T-cell-mediated anti-tumor activities, tumor-infiltrating T cells were injected in mice carrying autologous tumors and the mice treated with karonudib. We show that karonudib has heterogeneous anti-tumor effect on metastatic melanoma. Thus, based on the treatment responses, we could divide the 31 patient-derived xenografts in three treatment groups: progression group (32%), suppression group (42%), and regression group (26%). Furthermore, we show that karonudib has anti-tumor effect, irrespective of major melanoma driver mutations. Also, we identify high expression of ABCB1, which codes for p-gp pumps as a resistance biomarker. Finally, we show that karonudib treatment does not hamper T-cell-mediated anti-tumor responses. These findings can be used to guide future use of karonudib in clinical use with a potential approach as precision medicine

Ionization degree of the electron-hole plasma in semiconductor quantum wells

The degree of ionization of a nondegenerate two-dimensional electron-hole plasma is calculated using the modified law of mass action, which takes into account all bound and unbound states in a screened Coulomb potential. Application of the variable phase method to this potential allows us to treat scattering and bound states on the same footing. Inclusion of the scattering states leads to a strong deviation from the standard law of mass action. A qualitative difference between mid- and wide-gap semiconductors is demonstrated. For wide-gap semiconductors at room temperature, when the bare exciton binding energy is of the order of T, the equilibrium consists of an almost equal mixture of correlated electron-hole pairs and uncorrelated free carriers.Comment: 22 pages, 6 figure

Randomized Trial of Metformin, Ivermectin, and Fluvoxamine for Covid-19

BACKGROUND Early treatment to prevent severe coronavirus disease 2019 (Covid-19) is an important component of the comprehensive response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. METHODS In this phase 3, double-blind, randomized, placebo-controlled trial, we used a 2-by-3 factorial design to test the effectiveness of three repurposed drugs - metformin, ivermectin, and fluvoxamine - in preventing serious SARS-CoV-2 infection in nonhospitalized adults who had been enrolled within 3 days after a confirmed diagnosis of infection and less than 7 days after the onset of symptoms. The patients were between the ages of 30 and 85 years, and all had either overweight or obesity. The primary composite end point was hypoxemia (≤93% oxygen saturation on home oximetry), emergency department visit, hospitalization, or death. All analyses used controls who had undergone concurrent randomization and were adjusted for SARSCoV-2 vaccination and receipt of other trial medications. RESULTS A total of 1431 patients underwent randomization; of these patients, 1323 were included in the primary analysis. The median age of the patients was 46 years; 56% were female (6% of whom were pregnant), and 52% had been vaccinated. The adjusted odds ratio for a primary event was 0.84 (95% confidence interval [CI], 0.66 to 1.09; P=0.19) with metformin, 1.05 (95% CI, 0.76 to 1.45; P=0.78) with ivermectin, and 0.94 (95% CI, 0.66 to 1.36; P=0.75) with fluvoxamine. In prespecified secondary analyses, the adjusted odds ratio for emergency department visit, hospitalization, or death was 0.58 (95% CI, 0.35 to 0.94) with metformin, 1.39 (95% CI, 0.72 to 2.69) with ivermectin, and 1.17 (95% CI, 0.57 to 2.40) with fluvoxamine. The adjusted odds ratio for hospitalization or death was 0.47 (95% CI, 0.20 to 1.11) with metformin, 0.73 (95% CI, 0.19 to 2.77) with ivermectin, and 1.11 (95% CI, 0.33 to 3.76) with fluvoxamine. CONCLUSIONS None of the three medications that were evaluated prevented the occurrence of hypoxemia, an emergency department visit, hospitalization, or death associated with Covid-19

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

ФАКТОРЫ, ВЛИЯЮЩИЕ НА ИНТЕНСИВНОСТЬ БОЛЕВОГО СИНДРОМА В РАННЕМ ПОСЛЕОПЕРАЦИОННОМ ПЕРИОДЕ ПОСЛЕ ТОТАЛЬНОЙ АРТРОПЛАСТИКИ КОЛЕННОГО СУСТАВА

Purpose – to describe the relationship of selected socio-demographic, clinical, and surgical factors with the severity and patterns of postoperative pain during the first three days following total knee arthroplasty.Material and methods. The sample included 100 patients (93 women and 7 men; mean age 63.5±7.8 years) with osteoarthritis admitted for primary total knee arthroplasty. Prior to surgery, standard measures were used to assess preoperative pain and other symptoms, clinical manifestations of osteoarthritis, functional status of the knee, comorbidities, functional abilities, quality of life, and other patient characteristics. Physical, biochemical and surgical parameters of the perioperative period were also recorded. Patterns of daily changes in postoperative pain characteristics were investigated with the use of individual diaries. Results. All the analyzed indicators of postoperative pain progressively decreased during the three days after surgery (р0,001), including the number of daily hours of moderate to severe pain (р0,001). Pain levels were generally higher among women than among men (р = 0,009). Of the analyzed preoperative factors, higher levels postoperative pain were correlated with higher levels of anxiety (р = 0,029) and preoperative pain intensity (р = 0,029). Among the perioperative factors, surgery duration longer than 90 minutes was associated with higher levels of postoperative pain in activity (р = 0,012) and more hours of moderate/severe pain (р = 0,008). Characteristics of postoperative pain were unrelated to level of patient education, social or family status, employment, lifestyle, or any other clinical or laboratory variables.Conclusion. Of the many factors previously associated with postoperative pain, only gender, anxiety and level of preoperative pain confirmed their importance in this study. Among the perioperative factors, surgery duration, which varied by the type of implant, was significantly associated with postoperative pain levels. Цель исследования – установить взаимосвязь комплекса социально-демографических, когнитивных, клинических и хирургических факторов с интенсивностью и динамикой болевого синдрома в течение первых трех суток после тотального эндопротезирования коленного сустава.Материал и методы. В исследование было включено 100 больных гонартрозом, госпитализированных для первичного тотального эндопротезирования коленного сустава. Женщин было 93 (93%), мужчин – 7 (7%). Средний возраст пациентов составил 63,5±7,8 лет. С использованием специализированных тестов перед проведением хирургического вмешательства проведена детализированная оценка различных показателей болевого синдрома, выраженности клинических проявлений гонартроза и функционального состояния коленного сустава, параметров повседневной двигательной активности и качества жизни пациентов, а также особенностей сопутствующих заболеваний. Отдельно были проанализированы вариабельные физические, биохимические и хирургические параметры периоперационного периода. Суточная динамика изменения характеристик послеоперационного болевого синдрома исследована с использованием индивидуальных дневников как при разных видах нагрузок, так и в покое.Результаты. Все анализируемые показатели болевого синдрома прогрессивно уменьшались в течение трех дней после операции (р0,001), в том числе ежедневная продолжительность умеренной и сильной боли (р0,001). У женщин болевой синдром был более выражен, чем у мужчин (р = 0,009). Из проанализированных предоперационных факторов статистическая значимая положительная взаимосвязь была продемонстрирована для уровня тревожности (р = 0,029), интенсивности болевого синдрома (р = 0,029) и высокого уровня двигательной активности пациента (р = 0,012). Среди периоперационных факторов только продолжительность вмешательства более 90 мин коррелировала с интенсивностью боли (р = 0,008). Характеристики послеоперационного болевого синдрома не зависели от уровня образования пациента, социального или семейного статуса, вида занятости, особенностей образа жизни, а также каких-либо других клинических или лабораторных переменных.Заключение. Из многочисленных факторов, которые ассоциированы с уровнем послеоперационного болевого синдрома, только пол, тревожность и более высокий уровень предоперационной боли оказались статистически значимыми. Среди периоперационных факторов следует выделить продолжительность операции, которая зависела от вида имплантата и была статистически значимо ассоциирована с высоким уровнем послеоперационной боли.

Off-pump hepatic to azygos connection via thoracotomy for relief of fistulas after a Kawashima procedure: Ten-year results

Objectives: An almost universal incidence of developing pulmonary arteriovenous fistulas after the Kawashima operation has been reported. Exclusion of the hepatic venous flow from the pulmonary circulation causes the development of these malformations. Redirection of hepatic venous flow to the pulmonary circulation mostly leads to the regression of the arteriovenous fistulas. Methods: We analyzed 11 patients with arteriovenous fistulas that developed after the Kawashima operation. The hepatic-to-azygos shunts were performed with an off-pump technique through a lateral thoracotomy in all but one. Operative and postoperative data were retrospectively collected. Results: No intraoperative complications occurred, and no patient died in the hospital. Up to 10-year follow-up showed a significant postoperative improvement of patients' oxygen saturation and New York Heart Association class. Apart from 2 re-thoracotomies for bleeding in 1 patient, no complications occurred and no patient died during follow-up. Two other patients underwent reoperation for an undiagnosed additional hepatic vein. The improvement of patients' oxygen saturation and New York Heart Association class persisted during the follow-up period. Conclusions: The surgical connection can be performed safely with an off-pump technique that avoids the risks related to extracorporeal circulation and circulatory arrest. The results at 10 years follow-up confirmed the efficacy and safety of the surgical technique described