Amorphous FeCoCrSiB Ribbons with Tailored Anisotropy for the Development of Magnetic Elements for High Frequency Applications

The ferromagnetic resonance (FMR) in the frequency range of 0.5 to 12.5 GHz has been investigated as a function of external magnetic field for rapidly quenched Fe₃Co₆₇Cr₃Si₁₅B₁₂ amorphous ribbons with different features of the effective magnetic anisotropy. Three states of the ribbons were considered: as-quenched without any treatment; after relaxation annealing without stress at the temperature of 350 °C during 1 h; and after annealing under specific stress of 230 MPa at the temperature of 350 °C during 1 h. For FMR measurements, we adapted a technique previously proposed and tested for the case of microwires. Here, amorphous ribbons were studied using the sample holder based on a commercial SMA connector. On the basis of the measurements of the reflection coefficient S_11, the total impedance including its real and imaginary components was determined to be in the frequency range of 0.5 to 12.5 GHz. In order to confirm the validity of the proposed technique, FMR was also measured by the certified cavity perturbation technique using a commercial Bruker spectrometer operating at X-band frequency of 9.39 GHz. As part of the characterization of the ribbons used for microwave measurements, comparative analysis was performed of X-ray diffraction, optical microscopy, transmission electron microscopy, inductive magnetic hysteresis loops, vibrating sample magnetometry, magneto-optical Kerr effect (including magnetic domains) and magnetoimpedance data for of all samples.     

The Role of Social Support in Machismo and Acceptance of Violence Among Adolescents in Europe: Lights4Violence Baseline Results

PurposeTo analyze the potential association between social support, experiences of violence, and sociodemographic characteristics of adolescents and the likelihood of acceptance of violence and machismo in different European countries.MethodsCross-sectional design. We recruited 1,555 participants ages 13–16 from secondary schools in Alicante (Spain), Rome (Italy), Iasi (Romania), Matosinhos (Portugal), Poznan (Poland), and Cardiff (UK). We used linear regression models to identify how social support from teachers and parents, experiences of violence—dating violence, bullying, cyberbullying, abuse in childhood—and sociodemographic characteristics were associated with violent thinking, specifically: machismo and acceptance of violence. The analysis was stratified by sex.ResultsAcceptance of violence was higher for those who had lower perceived social support from parents (β_girls = ?154, p < .001; β_boys = ?.114, p = .019) for both sexes. Perpetration of bullying and/or cyberbullying was associated with higher scores for machismo and acceptance of violence for both sexes (β_girls = .067, p = .035; β_boys = .225, p < .001; (β_girls = .118, p < .001; β_boys = .210, p < .001). Being the victim of dating violence, having suffered physical and/or sexual abuse in childhood, and lower perceived social support from teachers were associated with higher scores for both machismo and acceptance of violence. These associations differed between girls and boys.ConclusionsMachismo and acceptance of violence are widely present amongst adolescents in different European countries. Our results suggest the importance of providing educational/psycho-educational interventions with boys and girls to prevent these attitudes and, in turn, prevent interpersonal violence, including bullying and dating violence.     

雌激素减少与代谢综合征关系的实验研究

目的：探讨雌激素减少与代谢综合征的相关性。方法:在基因库中搜索已知的对脂肪组织有影响的10个基因，筛选其启动子中可能存在的雌激素调控因子的基因。以不同月龄、不同基因型的卵泡刺激素受体敲除 (FORKO)雌鼠为动物模型，测量其腹内白色脂肪组织（WAT）重量、体重，计算腹内WAT与体重的比率；口服葡萄糖（2?g/kg），测快速血糖（0, 30, 60, 120?min）行葡萄糖耐量实验；用组织学方法观察脂肪细胞、肝脏细胞的形态；用放射免疫法测定血清瘦素。结果: ①在7个肥胖相关基因中找到了可能的雌激素调控位点；②FORKO雌鼠于3月龄时出现肥胖，腹内WAT的重量明显高于野生型（P＜0.05）；③FORKO雌鼠随月龄的增长葡萄糖耐量逐渐减低（P＜0.05）；④FORKO雌鼠腹内WAT细胞在3月龄时体积较小，表现为增生（P＜0.05），而在8个月时表现为肥大(P＜0.05)；⑤FORKO雌鼠于8月龄时WAT细胞、棕色脂肪（BAT）细胞及肝细胞内均有大量脂酯颗粒堆积；⑥月龄3～5个月的FORKO雌鼠空腹的血清瘦素水平均明显高于野生雌鼠(P＜0.05)。结论:FORKO雌鼠因雌激素减少而表现出腹型肥胖、高血糖、高瘦素和胰岛素抵抗等代谢紊乱，提示雌激素减少可导致代谢综合征。     

Influence of history of smoking on the physical capacity of older people

Among the elderly, smoking is related to death and it contributes to disability associated with chronic diseases. This study aims to verify the influence of a history of smoking on the physical capacity of elderly people, and its relationship with the gender. Elderly people beginning to practice physical activity reported questions about their smoking history and underwent a physical evaluation, consisted by hemodynamic data (blood pressure, heart rate and maximum oxygen consumption), body mass index (BMI), muscular strength, flexibility and balance. Mann-Whitney test and Spearman's test was used to data analysis. The sample consisted of 127 subjects, among whom 26.8% were ex-smokers. There were a higher number of nonsmoking women (p < 0.001) than others, and women smoked fewer packets per day (p = 0.047). Among the women, those ex-smokers were younger and more flexible in comparison with those nonsmokers (p < 0.05). Among the men, the ex-smokers were older and walked more slowly than nonsmokers (p < 0.05). There was a correlation between the BMI and duration of smoking time. Smoking cessation benefits the elderly, since the physical variables showed no long-term harm associated with the history of smoking when compared with those of elderly without this habit.     

Ibrutinib combinations in CLL therapy: scientific rationale and clinical results

Ibrutinib has revolutionized the treatment of chronic lymphocytic leukemia (CLL). This drug irreversibly inhibits Bruton tyrosine kinase (BTK) by covalently binding to the C481 residue in the BTK kinase domain. BTK is a pivotal protein for B cell receptor signaling and tissue homing of CLL cells. Preclinical investigations have established the importance of the B cell receptor pathway in the maintenance and survival of normal and malignant B cells, underscoring the importance of targeting this axis for CLL. Clinical trials demonstrated overall and progression-free survival benefit with ibrutinib in multiple CLL subgroups, including patients with relapsed or refractory disease, patients with 17p deletion, elderly patients, and treatment-naïve patients. Consequently, ibrutinib was approved by the US Food and Drug Administration for newly diagnosed and relapsed disease. Ibrutinib has transformed the treatment of CLL; however, several limitations have been identified, including low complete remission rates, development of resistance, and uncommon substantial toxicities. Further, ibrutinib must be used until disease progression, which imposes a financial burden on patients and society. These limitations were the impetus for the development of ibrutinib combinations. Four strategies have been tested in recent years: combinations of ibrutinib with immunotherapy, chemoimmunotherapy, cell therapy, and other targeted therapy. Here, we review the scientific rationale for and clinical outcome of each strategy. Among these strategies, ibrutinib with targeted agent venetoclax results in high complete response rates and, importantly, high rates of undetectable minimal residual disease. Although we concentrate here on ibrutinib, similar combinations are expected or ongoing with acalabrutinib, tirabrutinib, and zanubrutinib, second-generation BTK inhibitors. Future investigations will focus on the feasibility of discontinuing ibrutinib combinations after a defined time; the therapeutic benefit of adding a third agent to ibrutinib-containing combinations; and profiling of resistant clones that develop after combination treatment. A new standard of care for CLL is expected to emerge from these investigations.Subject terms: Combination drug therapy, Medical research     

Source apportionment of methane escaping the subsea permafrost system in the outer Eurasian Arctic Shelf

The East Siberian Arctic Shelf holds large amounts of inundated carbon and methane (CH₄). Holocene warming by overlying seawater, recently fortified by anthropogenic warming, has caused thawing of the underlying subsea permafrost. Despite extensive observations of elevated seawater CH₄ in the past decades, relative contributions from different subsea compartments such as early diagenesis, subsea permafrost, methane hydrates, and underlying thermogenic/ free gas to these methane releases remain elusive. Dissolved methane concentrations observed in the Laptev Sea ranged from 3 to 1,500 nM (median 151 nM; oversaturation by ∼3,800%). Methane stable isotopic composition showed strong vertical and horizontal gradients with source signatures for two seepage areas of δ¹³C-CH₄ = (−42.6 ± 0.5)/(−55.0 ± 0.5) ‰ and δD-CH₄ = (−136.8 ± 8.0)/(−158.1 ± 5.5) ‰, suggesting a thermogenic/natural gas source. Increasingly enriched δ¹³C-CH₄ and δD-CH₄ at distance from the seeps indicated methane oxidation. The Δ¹⁴C-CH₄ signal was strongly depleted (i.e., old) near the seeps (−993 ± 19/−1050 ± 89‰). Hence, all three isotope systems are consistent with methane release from an old, deep, and likely thermogenic pool to the outer Laptev Sea. This knowledge of what subsea sources are contributing to the observed methane release is a prerequisite to predictions on how these emissions will increase over coming decades and centuries.

The East Siberian Arctic Shelf (ESAS) is the world’s largest and shallowest shelf sea system, formed through inundation of northeast Siberia during sea level transgression in the early Holocene. The ESAS holds substantial but poorly constrained amounts of organic carbon and methane (CH₄). These carbon/methane stores are contained in unknown partitions as gas hydrates, unfrozen sediment, subsea permafrost, gas pockets within and below the subsea permafrost, and as underlying thermogenic gas (1–3). Methane release to the atmosphere from these compartments could potentially have significant effects on the global climate (4, 5), yet there are large uncertainties regarding the size and the vulnerability toward remobilization of these inaccessible and elusive subsea carbon/methane pools. Conceptual development and modeling have predicted that warming of the ESAS system by a combination of geothermal heat and climate-driven Holocene heat flux from overlying seawater, recently further enhanced by Anthropocene warming, may lead to thawing of subsea permafrost (6, 7). Subsea permafrost drilling in the Laptev Sea, in part at the same sites as 30 y ago, has recently confirmed that the subsea permafrost has indeed come near the point of thawing (8). In addition to mobilization of the carbon/methane stored within the subsea permafrost, its degradation can also lead to the formation of pathways for gaseous methane from underlying reservoirs, allowing further methane release to the overlying water column (3, 9).Near-annual ship-based expeditions to the ESAS over the past two decades have documented widespread seep locations with extensive methane releases to the water column (3, 10). Methane levels are often found to be 10 to 100 times higher than the atmospheric equilibrium and are particularly elevated in areas of strong ebullition from subsea gas seeps (“methane hotspots”). Similarly, elevated dissolved methane concentrations in bottom waters appear to be spatially related to the thermal state of subsea permafrost as deduced from modeling results and/or geophysical surveys (7, 9). Currently, we lack critical knowledge on the quantitative or even relative contributions of the different subsea pools to the observed methane release, a prerequisite for robust predictions on how these releases will develop. An important distinction needs to be made between pools that release methane gradually, such as methane produced microbially in shallow sediments during early diagenesis or in thawing subsea permafrost, versus pools with preformed methane that may release more abruptly once pathways are available, such as from disintegrating methane hydrates and pools of thermogenic (natural) gas below the subsea permafrost. Multidimensional isotope analysis offers a useful means to disentangle the relative importance of these different subsea sources of methane to the ESAS: Stable isotope data (δ¹³C-CH₄ and δD-CH₄) provide useful information on methane formation and removal pathways, and the radiocarbon content of methane (Δ¹⁴C-CH₄) helps to determine the age and methane source reservoir (see SI Appendix, text S1 for details on these isotope systematics and typical isotopic signatures for the ESAS subsea system).Here, we present triple-isotope–based source apportionment of methane conducted as part of the Swedish–Russian–US investigation of carbon–climate–cryosphere interactions in the East Siberian Arctic Ocean (SWERUS-C3) program. To this end, the distribution of dissolved methane, its stable carbon and hydrogen isotope composition, as well as natural radiocarbon abundance signature, were investigated with a focus on the isotopic fingerprint of methane escaping the seabed to pinpoint the subsea sources of elevated methane in the outer Laptev Sea.     

Characterization of "Yaa Chud" Medicine on the Thailand-Myanmar border: selecting for drug-resistant malaria and threatening public health

Multidrug-resistant Plasmodium falciparum malaria is a severe public health problem on the Thailand-Myanmar border. Many villagers buy packets of 4-5 mixed medicines ("yaa chud") from shops without medical assessment as their first-line malaria treatment. In 2000-2001 a local researcher purchased 50 yaa chud from 44 shops around Mae Sot, Thailand and Myawaddy, Myanmar (Burma), for his wife who was said to be pregnant with fever and drowsiness. The tablets/capsules were provisionally identified by appearance and active ingredients determined in a subset by using mass and atomic spectrometry. The most frequently detected active ingredients were acetaminophen (22%), chlorpheniramine (13.4%), chloroquine (12.6%), tetracycline/doxycycline (11.4%), and quinine (5.1%). Only seven bags contained potentially curative medicine for malaria. A total of 82% of the bags contained medicines contraindicated in pregnancy. Inappropriate, ineffective antimalarial drugs on the Thailand-Myanmar border are likely to increase malaria morbidity, mortality and health costs and engender the emergence and spread of antimalarial drug resistance.     

Clinical characteristics and long-term outcome in patients with heart failure complicating acute myocardial infarction

INTRODUCTION AND OBJECTIVES: To evaluate the clinical characteristics and prognosis of heart failure (HF) development in patients hospitalized for acute myocardial infarction (AMI). PATIENTS AND METHOD: Between May 1990 and March 2000, 836 consecutive patients were admitted with a diagnosis of AMI within 24 h of symptom onset. HF was defined as the presence of rales and a third heart sound with gallop, and evidence of pulmonary congestion on chest x-ray. It was diagnosed in 263 subjects (31.5%). RESULTS: The mean age of patients with HF (group 1) was 63.4 (11.4) years compared with 59.9 (11.6) years in those without HF (group 2) (P<.01). There were differences between groups 1 and 2 in history of diabetes (36% vs 20%; P<.001) or previous HF (9.2% vs 1.1%; P<.001). The reperfusion strategy used in patients with Q-wave infarction, with or without HF, was primary angioplasty in 15% and 14%, respectively (P=.81), and thrombolytic agents in 28% and 37%, respectively (P=.013). Patients with HF were more likely to develop recurrent angina (26.8% vs 19.6%; P=.02), pericarditis (17.5% vs 6.3%; P<.001), and atrial fibrillation (12.3% vs 5.1%; P<.01). In-hospital mortality in groups 1 and 2 was 15.6% and 2.3% (P<.001), respectively, and 10-year survival was 10% and 30%, respectively (P<.001). The variables associated with mortality were: age (HR=1.022; P<.001), hyperglycemia (HR=1.748 per 1.0-g/L increase; P<.001), leukocytosis (HR=1.035 per 1000-cell/.L increase; P<.001), and HF (HR=1.308; P=.028). CONCLUSIONS: AMI is still frequently complicated by HF, which increases short- and long-term morbidity and mortality. Heart failure, age, hyperglycemia, and leukocytosis at admission were independent predictors of mortality during follow-up.     

Antibodies to citrullinated alpha-enolase peptide 1 are specific for rheumatoid arthritis and cross-react with bacterial enolase

OBJECTIVE: To map the antibody response to human citrullinated alpha-enolase, a candidate autoantigen in rheumatoid arthritis (RA), and to examine cross-reactivity with bacterial enolase. METHODS: Serum samples obtained from patients with RA, disease control subjects, and healthy control subjects were tested by enzyme-linked immunosorbent assay (ELISA) for reactivity with citrullinated alpha-enolase peptides. Antibodies specific for the immunodominant epitope were raised in rabbits or were purified from RA sera. Cross-reactivity with other citrullinated epitopes was investigated by inhibition ELISAs, and cross-reactivity with bacterial enolase was investigated by immunoblotting. RESULTS: An immunodominant peptide, citrullinated alpha-enolase peptide 1, was identified. Antibodies to this epitope were observed in 37-62% of sera obtained from patients with RA, 3% of sera obtained from disease control subjects, and 2% of sera obtained from healthy control subjects. Binding was inhibited with homologous peptide but not with the arginine-containing control peptide or with 4 citrullinated peptides from elsewhere on the molecule, indicating that antibody binding was dependent on both citrulline and flanking amino acids. The immunodominant peptide showed 82% homology with enolase from Porphyromonas gingivalis, and the levels of antibodies to citrullinated alpha-enolase peptide 1 correlated with the levels of antibodies to the bacterial peptide (r2=0.803, P<0.0001). Affinity-purified antibodies to the human peptide cross-reacted with citrullinated recombinant P gingivalis enolase. CONCLUSION: We have identified an immunodominant epitope in citrullinated alpha-enolase, to which antibodies are specific for RA. Our data on sequence similarity and cross-reactivity with bacterial enolase may indicate a role for bacterial infection, particularly with P gingivalis, in priming autoimmunity in a subset of patients with RA.