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The aim of this study was to examine the altering patterns in clinical characteristics and severity of acute post-streptococcal glomerulonephritis (APSGN) in children.We analyzed the medical records of 119 children who were diagnosed with APSGN from 1987 to 2018, retrospectively. The patients were divided into two groups: Group I (n=72, before 1998) and Group II (n=47, after 1998). Clinical, radiologic, and laboratory findings were compared between the two groups.The clinical manifestations, including vomiting (20.8% vs. 4.3%, p=0.014), oliguria (40.3% vs. 19.1%, p=0.016), and generalized edema (86.1% vs. 63.8%, p=0.005), were statistically less frequent since 1998. Pulmonary edema on chest X-ray (22.7% vs. 4.4%, p=0.014) was less frequent in Group II than in Group I. The level of BUN (23.3±19.3 vs. 18.8±11.2, p=0.009) was lower in Group II than in Group I, while that of creatinine was not significantly different between the two groups. C3 level was an independent factor for predicting the development of edema (odds ratio [OR]: 1.034, 95% CI: 1.010-1.060, p=0.006) and acute nephritic symptoms (≥2) (OR: 0.974, 95% CI: 0.952-0996, p=0.020). It was also negatively correlated with an increasing number of acute nephritic symptoms, including oliguria and edema, in patients with APSGN (R=-0.182, p=0.048).This study demonstrated that APSGN had favorable clinical manifestations and severity over the past 30 years. The monitoring of C3 levels can be used to assess the disease severity and risk of complications, including edema and oliguria, which are decreasing in South Korean children.

Catheter probe endoscopic ultrasonography (C-EUS) by ultrasonographic jelly-filled method has been used to evaluate esophageal subepithelial tumors (SETs). Ultrasonographic jelly is safe on the skin, but its internal safety has not been demonstrated. The jelly stored at room temperature is easily injected into the esophagus through the instrument channel of the endoscope. However, using jelly stored at room temperature remains problematic because the jelly is drained rapidly. We used cold lubricating jelly and an intravenous extension tube to resolve these problems. In this study, we evaluated the safety and efficacy of cold lubricating jelly-filled method. The medical records of patients who underwent C-EUS by using water or cold lubricating jelly-filled method for esophageal SETs from March 2013 to September 2016 in Gangneung Asan hospital were reviewed. Clinical characteristics and EUS findings were evaluated retrospectively. Image quality and procedure time between water and cold lubricating jelly-filled method were compared retrospectively. This study included 138 patients (74 males, 64 females) with esophageal SET with a mean age of 57.1 ± 11.1 years. Thirty-four patients had lesions in the upper esophagus, 58 patients had lesions in the middle esophagus, and 46 patients had lesions in the lower esophagus. The EUS diagnoses were leiomyoma (82.6%), hemangioma (4.3%), extrinsic compressive lesion (3.6%), granulosa cell tumor (2.9%), ectopic calcification (1.4%), cyst (1.4%), lipoma (0.7%), varix (0.7%), and inconclusive lesion (2.2%). The mean image score in the cold lubricating jelly filled-method group was higher than that in the water-filled method group (3.2 ± 0.7 vs. 2.8 ± 0.7, P = 0.002). The procedure time in the cold lubricating jelly filled-method group was shorter than that in the water-filled method group (10 minutes 27 seconds ± 4 minutes 22 seconds versus 13 minutes 20 seconds ± 6 minutes 20 seconds, P = 0.045). No procedure-related complication was observed. C-EUS using the cold lubricating jelly-filled method seems to provide better image quality and shorter procedure time compared with C-EUS using the water-filled method.

SummaryBackground Non-alcoholic fatty liver disease (NAFLD) is known to be associated with polycystic ovary syndrome (PCOS). However, most studies investigated the prevalence of NAFLD in obese PCOS patients. Aim To compare the prevalence of non-obese NAFLD in women with or without PCOS, and to assess an independent association between PCOS and NAFLD in a non-obese Asian cohort. Methods This was a case–control study using a prospective PCOS cohort. After subjects with other potential causes of chronic liver disease were excluded, 275 non-obese women with PCOS and 892 non-obese controls were enrolled. NAFLD was determined by hepatic ultrasonography. Main outcomes were the prevalence of NAFLD on hepatic ultrasonography between non-obese women with or without PCOS, and an independent association between non-obese NAFLD and PCOS. Results Non-obese women with PCOS had a significantly higher prevalence of NAFLD than those without PCOS (5.5% vs. 2.8%, P = 0.027). PCOS was associated with non-obese NAFLD (odds ratio: 2.62, 95% confidence intervals: 1.25–5.48) after adjustment for age and body mass index (BMI). In women with PCOS, the level of androgenicity represented by free testosterone or free androgen index was associated with NAFLD after adjustment for age, BMI, lipid profile, insulin resistance or glycaemic status. Conclusions Non-obese NAFLD is more prevalent in women with polycystic ovary syndrome than in those without. In non-obese patients with polycystic ovary syndrome, hyperandrogenemia may be an independent risk factor for non-obese NAFLD.

In order to solve the problems of the warhead initiation system due to the low safety of conventional detonator arrays and the poor synchronization of the explosion logic network, as well as the MEMS batch integration requirements, a research on EFI multi-point synchronous initiation technology based on MEMS technology was carried out. Explosive foil was prepared by magnetron sputtering and photolithography. SU-8 photoresist flying sheet layer and acceleration chamber were prepared on the bridge foil by UV thick glue technology, and single-point, two-point parallel and three-point parallel were realized. The two batches of two and a total of four points and three strings of three and a total of nine points explosion foil initiators were batch-integrated and tested for the synchronism of the flying sheet effect. The test results show that the average time between two points, three points, and four points is less than 80ns, and the synchronization time is small; the average time at nine points is less than 200ns, and the synchronization time is large.

Background:Western countries experience an increasing demand for care, particularly for inflammatory arthritis (IA), while the healthcare budget decreases1. The innovative value-based primary care strategy2includes integrated care networks, where primary and secondary care bundle their expertise to improve patient value by providing the right care at the right place.General practitioners (GPs) have difficulties recognising IA, leading up to only 20% IA diagnoses of all newly referred arthralgia patients. However, since IA needs to be treated as early as possible to overcome progression, it is worthwhile to analyse whether integrated care networks have an impact on patient outcomes and cost-effectiveness. Triage by a rheumatologist in a primary care setting is one of the most promising integrated care networks for efficient referrals3.Objectives:To assess the effect of triage by a rheumatologist in a primary care setting in patients suspect for inflammatory arthritis.Methods:The present study follows a cluster randomized controlled trial design. The intervention, triage by a rheumatologist in a local primary care centre, will be compared to usual care. Usual care means that patients are referred to a rheumatology outpatient clinic based on the opinion of the general practitioner.The primary outcome is the frequency of IA diagnoses assessed by a rheumatologist. Patient reported outcome measures (PROMs (EQ-5D)) and costs (work productivity (iPCQ) and healthcare utilization (iMCQ)) were determined at baseline, after three, six and twelve months. The target was to include 267 patients for each study group (power level 0.8). Since this study is still ongoing we can only show first results on the efficiency of referrals.Results:In the period between February 2017 and December 2019 a total of 543 participants were included; 275 in the usual care group and 268 in the triage group. Mean age (51.3 ± 14.6 years) and percentage of men (23.6%) were comparable between groups (page=0.139; psex=0.330).The preliminary data show that the number of referred patients in the triage group is n=28 (10.5%) (Fig. 1). 32 patients (11.9%) were not referred directly but advice was given for additional diagnostics. Since all patients in the usual care group were referred there is a decrease of at least 77.6% in referrals when rheumatologists are participating in the integrated practice units.Preliminary data on diagnosis are available for all referred patients in the triage group and for n=137 (49.8%) in the usual care group at this point. In the triage group n=18 (64.2%) of referred patients were diagnosed with IA (6.7% of the total study population). In the usual care group this was n=52 (38.0%) of the patients yet diagnosed.Conclusion:These preliminary results of an integrated care network are promising. Approximately three-quarters of all patients can be withheld from expensive outpatient care. PROMs data and cost-effectiveness analysis will give clear answers in order to provide evidence whether this integrated care network can be implemented as a standard of care.References:[1] Rijksoverheid. (2018). Bestuurlijk akkoord medisch-specialistische zorg 2019 t/m 2022.https://www.rijksoverheid.nl/.[2] Porter ME, Pabo EA, Lee TH. (2013). Redesigning Primary Care: a strategic vision to improve value by organizing around patients’ needs. Health affairs, 32(3);516-525[3] Akbari A, et al. (2008). Interventions to improve outpatient referrals from primary care to secondary care. Cochrane Database Syst Rev, 4,CD005471.Disclosure of Interests:None declared

Background SOR is approved as 1L therapy for pts with aHCC, but there is still an unmet need to prolong survival and improve tolerability. This phase III study compared clinical efficacy and safety of NIVO with SOR as 1L therapy in pts with aHCC. Methods Systemic therapy–naive pts aged ≥18 years with aHCC were randomized 1:1 to NIVO (240mg IV Q2W) or SOR (400mg oral BID). Primary endpoint was overall survival (OS). Additional endpoints were objective response rate (ORR) and progression-free survival (PFS) by blinded independent central review per RECIST v1.1, efficacy by tumor programmed death ligand 1 (PD-L1) expression, and safety. Results 743 pts with aHCC were randomized to NIVO (n=371) or SOR (n=372) with minimum follow-up of 22.8 months at data cutoff. OS did not meet the predefined threshold of statistical significance (HR 0.84, P=0.0419). Median OS (mOS) was 16.4mo for NIVO and 14.7mo for SOR (HR 0.85 [95% CI: 0.72–1.02]; P=0.0752). Clinical benefit was observed across predefined subgroups, including hepatitis infection status, presence of vascular invasion and/or extrahepatic spread, and region (Asia vs non-Asia). ORR was 15% for NIVO (14 pts with complete response [CR]) and 7% for SOR (5 pts with CR; Table). Grade 3/4 treatment-related adverse events were reported in 81 pts (22%) in the NIVO arm and 179 pts (49%) in the SOR arm and led to discontinuation in 16 (4%) and 29 (8%) pts, respectively. No new safety signals were observed with NIVO. 140 pts (38%) in the NIVO arm and 170 pts (46%) in the SOR arm received subsequent therapy. Additional OS analyses and patient-reported outcomes will be presented to support the benefit of NIVO.Table: LBA38_PREfficacy resultsTable: LBA38_PRNIVOSORn=371n=372Median OS (95% CI), mo16.4 (13.9–18.4)14.7 (11.9–17.2)12-mo OS rate, % (95% CI)59.7 (54.4–64.6)55.1 (49.8–60.1)24-mo OS rate, % (95% CI)36.8 (31.8–41.8)33.1 (28.3–38.0)Median PFS, mo (95% CI)3.7 (3.1–3.9)3.8 (3.7–4.5)ORR, n (%)57 (15)26 (7)BOR, n (%)Complete response14 (4)5 (1)Partial response43 (12)21 (6)ORR by baseline tumor PD-L1 expression, n/n (%)PD-L1 ≥1%20/71 (28)6/64 (9)PD-L1 Conclusions Though the primary endpoint of OS did not achieve statistical significance vs SOR, NIVO showed clinically meaningful improvements in OS, ORR, and CR rate as 1L treatment for aHCC. NIVO demonstrated a favorable safety profile consistent with previous reports. Clinical trial identification NCT02576509. Editorial acknowledgement Writing and editorial assistance was provided by Andrea L. Hammons of Parexel International (Waltham, MA, USA) and funded by Bristol-Myers Squibb. Legal entity responsible for the study Bristol-Myers Squibb. Funding Bristol-Myers Squibb. Disclosure T. Yau: Honoraria (institution), Advisory / Consultancy: Bristol-Myers Squibb. R.S. Finn: Honoraria (self), Speaker Bureau / Expert testimony: AstraZeneca; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (self): Bayer; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution): Eisai; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution): Eli-Lilly; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution): Merck; Honoraria (self), Speaker Bureau / Expert testimony: Novartis; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (self): Pfizer; Honoraria (self), Speaker Bureau / Expert testimony: Roche/ Genentech. A. Cheng: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Ono Pharmaceutical; Advisory / Consultancy: Exelixis; Advisory / Consultancy: Nucleix Ltd.; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche/Genentech; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: IQVIA; Advisory / Consultancy: Merck Sharp Dohme; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bayer Yakuhin; Speaker Bureau / Expert testimony: Amgen Taiwan; Advisory / Consultancy: Ispen; Advisory / Consultancy: Bayer Schering Pharma; Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Eisai; Advisory / Consultancy: Merck Serono; Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Novartis. P. Mathurin: Honoraria (self), Speaker Bureau / Expert testimony: Ipsen; Honoraria (self), Speaker Bureau / Expert testimony: Eisai; Honoraria (self), Speaker Bureau / Expert testimony: MSD; Honoraria (self), Speaker Bureau / Expert testimony: Bayer Healthcare ; Honoraria (self), Speaker Bureau / Expert testimony: AbbVie; Honoraria (self), Speaker Bureau / Expert testimony: Gilead; Honoraria (self), Speaker Bureau / Expert testimony: Servier; Honoraria (self), Speaker Bureau / Expert testimony: Sanofi. J. Edeline: Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (self), Speaker Bureau / Expert testimony: MSD; Honoraria (self), Speaker Bureau / Expert testimony: AstraZeneca; Honoraria (self), Speaker Bureau / Expert testimony: IPSEN; Honoraria (self), Speaker Bureau / Expert testimony: Eisai; Honoraria (self), Speaker Bureau / Expert testimony: Bayer; Travel / Accommodation / Expenses: Amgen. M. Kudo: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Bayer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Eisai; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Advisory / Consultancy: Ono; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Medico's Hirata; Research grant / Funding (institution): Otsuka; Research grant / Funding (institution): Taiho; Research grant / Funding (institution): Astellas Pharma; Research grant / Funding (institution): Chugai; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): EA Pharma; Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Gilead. J.J. Harding: Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (self), Speaker Bureau / Expert testimony: Eisai; Honoraria (self), Speaker Bureau / Expert testimony: Exelexis; Honoraria (self), Speaker Bureau / Expert testimony: Elly Lilly ; Honoraria (self), Speaker Bureau / Expert testimony: CytomX; Honoraria (self), Speaker Bureau / Expert testimony: QED. P. Merle: Advisory / Consultancy: Bayer; Advisory / Consultancy, Research grant / Funding (institution): IPSEN; Advisory / Consultancy: Eisai; Advisory / Consultancy: Lilly; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Merck; Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy: AstraZeneca. O. Rosmorduc: Honoraria (self): Bayer; Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy: Sirtex; Honoraria (self): Eisai. L. Wyrwicz: Research grant / Funding (self): Bristol-Myers Squibb; Research grant / Funding (self): Beigene; Research grant / Funding (self): Eisai. E. Schott: Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Bayer. S.P. Choo: Honoraria (self), Speaker Bureau / Expert testimony: Bayer; Honoraria (self), Speaker Bureau / Expert testimony: Lilly; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS; Honoraria (self), Advisory / Consultancy: Sirtex; Honoraria (self), Advisory / Consultancy: Eisai; Honoraria (self), Advisory / Consultancy: Ipsen. R.K. Kelley: Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Adaptimmune; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Exelixis; Honoraria (self), Speaker Bureau / Expert testimony, IDMC membership: Genentech/Roche; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Regeneron; Research grant / Funding (institution): AstraZeneca. D. Begic: Full / Part-time employment: Bristol-Myers Squibb. J. Neely: Shareholder / Stockholder / Stock options, Full / Part-time employment: Bristol-Myers Squibb. J. Anderson: Shareholder / Stockholder / Stock options, Full / Part-time employment: Bristol-Myers Squibb. B. Sangro: Advisory / Consultancy: Adaptimmune; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bayer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy: BTG; Advisory / Consultancy: H3 Biomedicine; Advisory / Consultancy, Speaker Bureau / Expert testimony: Ipsen; Advisory / Consultancy: Lilly; Advisory / Consultancy: Merck; Advisory / Consultancy: Onxeo; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Sirtex Medical; Advisory / Consultancy: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: Terumo. All other authors have declared no conflicts of interest.

As the awareness of public health/safety becomes important and the desire to provide clean/safe indoor air in a sustainable way increases, air filtration technology has become essential at urban built facilities, which are challenged by significant outdoor air pollution due to dense population and heavy traffic. To provide comparable/objective data for designers and professionals of gas-phase filtration equipment in HVAC systems, it is important to understand the performance and characteristics of possible filter medium candidates within a reasonable testing period at low levels of target hazard concentration (typically, ∼0.05 ppm). The present study investigated the 2000-time scale-down evaluation evidence and its behind reasons between practical high-concentration tests (∼100 ppm NO

We present the experimental results of magnetization measurements on thiol-capped gold nanoparticles (Au-SR NPs) synthesized in a two-phase liquid-liquid system. The size of particles ranged from 2.0 to 3.5 nm with an average size of 2.8 nm. The magnetic properties of Au-SR NPs were characterized by a mixture of ferromagnetic, paramagnetic and diamagnetic components. Magnetization curves showed the hysteresis behavior typical of a ferromagnet over the whole temperature (T) range investigated (2 K to 300 K) whereas M(H) did not saturate, not even at low T, implying the existence of a paramagnetic component. The negative slope of M(H) observed at high T demonstrated that a diamagnetic component was also considerable. From a theoretical fit, we obtained effective values of parameters such as the paramagnetic effective moment, μp = 5.7 μB, and the diamagnetic susceptibility, χd = −1.7 ×10−7 emu/gOe. In addition, the T-dependence of the ferromagnetic component Mf (T) was extracted from the experimental M(T), and its characteristics are discussed in the light of the mean field model.

We have investigated the SAR of a series of pyrimidinone-containing Cdc7 kinase inhibitors. A wide range of amine substitutions give potent compounds with activities (K(i)) less than 1nM. Kinase selectivity is reasonable and cytotoxicity corresponds to inhibition of MCM2 phosphorylation.

In search for magnetically active carbon structures, we have undertaken the magnetic force microscopy study of intrinsic defects at the surface of highly oriented pyrolytic graphite. Most of the observed defects, such as ridges and cleavage edges, are found magnetically inert. However, some of the observed sharp cleavage edges do show magnetic activity - a built-in surface magnetization, which reveals itself as the magnetic force gradient signal sensitive to the polarity of the tip magnetization. These results indicate the existence of a defect related magnetism at room temperature on graphite surface.

Detailed, country‐specific epidemiological data are needed to characterize the burden of chronic hepatitis C virus (HCV) infection around the world. With new treatment options available, policy makers and public health officials must reconsider national strategies for infection control. In this study of 15 countries, published and unpublished data on HCV prevalence, viraemia, genotype, age and gender distribution, liver transplants and diagnosis and treatment rates were gathered from the literature and validated by expert consensus in each country. Viraemic prevalence in this study ranged from 0.2% in Iran and Lebanon to 4.2% in Pakistan. The largest viraemic populations were in Pakistan (7001000 cases) and Indonesia (3187000 cases). Injection drug use (IDU) and a historically unsafe blood supply were major risk factors in most countries. Diagnosis, treatment and liver transplant rates varied widely between countries. However, comparison across countries was difficult as the number of cases changes over time. Access to reliable data on measures such as these is critical for the development of future strategies to manage the disease burden.

The total number, morbidity and mortality attributed to viraemic hepatitis C virus (HCV) infections change over time making it difficult to compare reported estimates from different years. Models were developed for 15 countries to quantify and characterize the viraemic population and forecast the changes in the infected population and the corresponding disease burden from 2014 to 2030. With the exception of Iceland, Iran, Latvia and Pakistan, the total number of viraemic HCV infections is expected to decline from 2014 to 2030, but the associated morbidity and mortality are expected to increase in all countries except for Japan and South Korea. In the latter two countries, mortality due to an ageing population will drive down prevalence, morbidity and mortality. On the other hand, both countries have already experienced a rapid increase in HCV‐related mortality and morbidity. HCV‐related morbidity and mortality are projected to increase between 2014 and 2030 in all other countries as result of an ageing HCV‐infected population. Thus, although the total number of HCV countries is expected to decline in most countries studied, the associated disease burden is expected to increase. The current treatment paradigm is inadequate if large reductions in HCV‐related morbidity and mortality are to be achieved.

Although recent studies have shown that several pro-inflammatory proteins can be used as biomarkers for atherosclerosis, the mechanism of atherogenesis is unclear and little information is available regarding proteins involved in development of the disease. Atherosclerotic tissue samples were collected from patients in order to identify the proteins involved in atherogenesis. The protein expression profile of atherosclerosis patients was analysed using two-dimensional electrophoresis-based proteomics. Thirty-nine proteins were detected that were differentially expressed in the atherosclerotic aorta compared with the normal aorta. Twenty-seven of these proteins were identified in the MS-FIT database. They are involved in a number of biological processes, including calcium-mediated processes, migration of vascular smooth muscle cells, matrix metalloproteinase activation and regulation of pro-inflammatory cytokines. Confirmation of differential protein expression was performed by Western blot analysis. Potential applications of the results include the identification and characterization of signalling pathways involved in atherogenesis, and further exploration of the role of selected identified proteins in atherosclerosis.

Akt is a serine/threonine kinase that transduces survival signals from survival/growth factors. Deregulation and signal imbalance in cancer cells make them prone to apoptosis. Upregulation or activation of Akt to aid the survival of cancer cells is a common theme in human malignancies. We have developed small-molecule Akt inhibitors that are potent and specific. These Akt inhibitors can inhibit Akt activity and block phosphorylation by Akt on multiple downstream targets in cells. Synergy in apoptosis induction was observed when Akt inhibitors were combined with doxorubicin or camptothecin. Akt inhibitor-induced enhancement of topoisomerase inhibitor cytotoxicity was also evident in long-term cell survival assay. Synergy with paclitaxel in apoptosis induction was evident in cells pretreated with paclitaxel, and enhancement of tumor delay by paclitaxel was demonstrated through cotreatment with Akt inhibitor Compound A (A-443654). Combination with other classes of chemotherapeutic agents did not yield any enhancement of cytotoxicity. These findings provide important guidance in selecting appropriate classes of chemotherapeutic agents for combination with Akt inhibitors in cancer treatment.

In this article several aspects concerning the induction of magnetic ordering in graphite via proton bombardment using nuclear nanoprobes are addressed such as proton range and lateral straggling, defect densities, heat load, and simultaneous impurity analysis via particle induced X-ray emission.

The magnetoresistance of step edges in magnetite films was systematically studied. An enhancement of the magnetoresistance by the introduction of step edges was observed, especially in the high-field regime. This was modelled by spin-disorder scattering. The analysis revealed magnetic cluster formation at the step edges.

The chemical and optical features of nano-crystalline rare earth ions-doped (Er, Tb:) Si thin films, which were prepared by RF magnetron sputter techniques, were investigated as a function of the amount of Er and Tb doping on the Si films. The structural and chemical features are related with the photoluminescence (PL) phenomena of the films. The PL phenomena were observed, owing to the electronic structure of Er and Tb ions as well as Si nano-crystallites in the films.

In this study ferromagnetic microstructures were created in highly oriented pyrolitic graphite (HOPG) by proton microbeam irradiation. For this purpose, spots of 1, 2 × 2 and 3.5 × 3.5 μm 2 were irradiated with ion fluences ranging from 3.1 × 10 16 to 4.7 × 10 19 cm −2 using 2.25 MeV proton and 1.5 MeV helium ion microbeams. As calculated by SRIM2003 simulations, the corresponding defect densities in the near surface region are between 3 × 10 19 and 4 × 10 22 cm −3 for the proton irradiation. The irradiated spots, which were characterized with atomic force microscopy (AFM) and magnetic force microscopy (MFM), show a clear swelling of the HOPG crystal proportional to the ion fluence. Strong magnetic force gradients were found even for the lowest proton fluences. Contrary to the topography, the magnetic force gradient changes after the application of a magnetic field. This rules out that the magnetic signals arise from topographical changes. Therefore, the MFM measurements reveal the existence of ferromagnetic domains in localized, disordered HOPG regions. On the contrary, helium ion irradiation of HOPG leads to much weaker magnetic signals only, which indicates that hydrogen plays a significant role in the formation of the magnetic moments and ordering. Very recently, the existence of ferromagnetism in ion beam irradiated HOPG was confirmed by SQUID measurements.

The recently found ferromagnetic signals in pure graphite and in polymerised fullerenes are received mainly with scepticism by most of the scientific community. Actually, before those results were published, there were already several reports claiming an unusually large magnetization in pyrolytic carbon and oxidised fullerenes, without attracting the attention of the community. This scepticism may be well founded since not always a careful and systematic impurity study was provided to quantify the influence of ferromagnetic impurities. In this article and after a brief review of the existing data on magnetic carbon, we present and discuss recently obtained results on the ferromagnetism (or ferrimagnetism) induced by proton irradiation on pure pyrolytic graphite, which strengthen the importance of hydrogen in the formation of the magnetic ordering. The overall results indicate that room-temperature ferromagnetism in carbon-based structures containing only p- and s-electrons is a reality.

We have investigated Pb adsorption on Si(0 0 1)-2 × 1 at room temperature (RT) and 78 K, using a low temperature (LT) scanning tunneling microscope. Pb deposition at RT exhibits 1-D chain structures in good agreement with previous works at less than 0.5 ML coverage, however, we find that the buckling of Pb dimers alone cannot explain the configurations such as locally coexisting (2 × 2) and c(2 × 4) phases. At RT and LT, C-type defects existing prior to Pb deposition play an important role as nuclei for the initial adsorption of Pb ad-dimers and determine the buckling direction. For LT deposition, a high density of short Pb units are found, including single Pb monomers. The existence of single Pb adatoms was verified using tip-induced molecular dissociation to split Pb ad-dimers into two single Pb adatoms.

In this study a C60 polymer has been characterized for the first time with respect to impurity content and ferromagnetic properties by laterally resolved particle induced X-ray emission (PIXE) and magnetic force microscopy (MFM) in order to prove the existence of intrinsic ferromagnetism in this material. In the sample studied the main ferromagnetic impurity found was iron with an average concentration of 175 ± 16 μg/g within the sample volume probed by the ion beam. However, the Fe distribution is very inhomogeneous and characterized by micrometer-large impurity grains of almost pure iron surrounded by an almost pure carbon matrix. With MFM, the ferromagnetic properties have been investigated both in pure and contaminated regions of the sample as determined by PIXE. We found that ∼30% of the area of pure regions (concentration of magnetic impurities

SummaryWe developed an effective detection method for wood-decaying fungi by hybridization of immobilized Sequence-Specific Oligonucleotide Probes with florescent-labeled PCR-amplified fungal rDNA internal transcribed spacer sequences. This method takes advantage of both the sequence specificity of Southern blot hybridization and the sensitivity of the previously reported PCR-based fungal species identification methods. Bothin vitrocultured fungal strains and naturally decaying wood samples were used to demonstrate that this method is robust and practical for detection of incipient wood-decaying fungi. It can be a useful tool for microbial ecology, plant pathology, protection of wood products in service, preservation efforts for high-value furniture and wood-based art and DNA fingerprinting for tracking the source of contamination of wood decay fungi.

A C60 polymer has been characterized for the first time with respect to impurity content and ferromagnetic properties by laterally resolved particle induced X-ray emission (PIXE), superconducting quantum interference device (SQUID) and magnetic force microscopy (MFM) in order to detect intrinsic ferromagnetic domains. In parts of the pure regions (concentration of magnetic impurities

The phototransformation of bulk C60 and laser- and electron-beam treatment of C60 films in air changes their magnetic properties. Nonlinear magnetization is observed only for samples irradiated in the presence of oxygen, while, in the case of pressure-polymerized C60, oxygen adversely affects the magnetic properties. The contrasting roles of oxygen in these processes are discussed. Magnetic force microscopy shows that laser- and electron-beam irradiation of fullerene films produces magnetic images which are highly correlated with the topographic images.

To evaluate rheumatologists' adherence to a low Disease Activity Score (DAS)-steered treat-to-target (T2T) strategy in treatment of patients with rheumatoid arthritis (RA) and to assess associated conditions.Data of the BeSt study were used, a multicenter T2T strategy trial with 10-year followup. During 3 monthly visits, the physician answered questions about satisfaction with level of RA suppression, agreement with the study protocol, and agreement with the DAS. Associations between the answers and nonadherence were evaluated.Protocol adherence decreased over time from 100% to 60% per visit, with an average over time of 79%. Rheumatologists mostly agreed with the DAS (80-90% of visits over time) and were satisfied with the treatment steps (75-90%) and with the level of RA suppression (85-90%). The odds for protocol violation were higher when the rheumatologist disagreed with the DAS (odds ratio [OR] 2.3, 95% confidence interval [95% CI] 2.0-2.7 when they thought the DAS overestimated actual disease activity; OR 2.5, 95% CI 2.0-3.1 when they thought the DAS underestimated actual disease activity) or with the next required treatment step (OR 3.0, 95% CI 2.5-3.5), and when the physician was dissatisfied with disease suppression (OR 1.3, 95% CI 1.1-1.6).Rheumatologists generally agreed with and followed a 10-year followup DAS-steered T2T strategy. Disagreement with the DAS or the required treatment and dissatisfaction with the level of disease suppression were risk factors for nonadherence. These results indicate the feasibility of continued protocol-driven T2T therapy. For daily practice, adherence to T2T therapy might be improved by adopting the structure components of a clinical trial.

The low-frequency noise in epitaxial La0.7Sr0.3Mn1-xFexO3 thin films with x = 0, 0.08 and 0.12 has been studied as a function of magnetic field (up to 1500 G). At zero external magnetic field (B = 0 G), there is no appreciable peak in the normalized noise power spectral density (PSD) for x = 0 thin films; however, a peak does appear for x = 0.08 and 0.12 thin films near the metal–insulator transition temperature (Tp), which is below the Curie temperature. Unlike the resistivity, the noise PSD does not change with the doping level (x) at B = 0 G; however, at B = 1500 G the noise PSD decreases with x. At a low external magnetic field of B < 1500 G, there is no or a small thermal hysteresis in the noise PSD for all three differently doped samples; however, at B = 1500 G there appears a large thermal hysteresis for all samples. The contribution of magnetic domain fluctuations is a possible origin for the noise PSD.

The low-frequency 1/f voltage noise of epitaxial La0.7Sr0.3Mn0.92Fe0.08O3 thin films has been studied as a function of temperature (80-300 K) and magnetic field (up to 1500 G). It is found that the noise power spectral density (PSD) shows a peak at T≈238 K which coincides with the peak temperature of the resistivity, and is below the Curie temperature. When a small magnetic field of 1500 G is applied, the noise PSD shows a large thermal hysteresis and changes with the magnetic history. This thermal hysteresis, lacking at B = 0, is distinctively different from other reported results on manganites without Mn-site doping. The origin of the noise peak at B = 0 is analysed on the basis of the magnetic fluctuation, and the scaling analysis of the normalized noise PSD is consistent with a three-dimensional random-void percolation model. The thermal hysteresis of the noise PSD further supports the assertions of a contribution from magnetic fluctuations and of a spin-dependent conduction process in Fe-doped colossal-magnetoresistance materials.

The low-frequency noise power spectral density (PSD) of highly c-axis oriented YBa2Cu3O7-δ thin-film microbridges is measured in the temperature range 77-300 K. At room temperature, the value of the Hooge parameter, γ, is 1.8×10-3, which is in the range of ordinary metal films. In the normal state, the noise PSD shows the generic `1/f noise' behaviour and decreases as the temperature is decreased. The experimental data obtained in the normal state cannot be described reasonably well by Dutta-Horn's thermally activated model. Moreover, in the transition temperature (Tc) region, the noise PSD shows 1/fα behaviour with α>1 and a noise peak appears. The noise increment in the Tc region can be explained by dimensional crossover in this novel percolation noise effect.

BACKGROUND: There are still insufficient clinical reports about quality-switched Nd:YAG laser (QSNYL) in the treatment of acquired bilateral nevus of Otalike macules (ABNOMs) in Asians. OBJECTIVE: To analyze the efficacy and side-effect profiles of QSNYL treatment of ABNOMs in Korean skin. METHODS: A prospective study was designed to follow 10 Korean patients with ABNOMs through laser treatment until maximal eradication of the lesions had been achieved. RESULTS: Five patients (50%) with ABNOMs were treated with excellent or good results. The more treatments a patient underwent, the greater the possibility of improvement. There were no cases of persistent skin textural change or persistent erythema. CONCLUSION: The clinical data support QSNYL being a beneficial alternative tool for treating ABNOMs in brown skin. This is, to the best of the authors' knowledge, the first report about laser treatment of ABNOMs using QSNNL.

The tensile properties and microstructures of AA6061/SiCp composites fabricated by the pressureless infiltration method under a nitrogen atmosphere were examined. Since the spontaneous infiltration of molten AA6061 into the powder bed containing SiCp occurred at 800 °C for 1 hour under a nitrogen atmosphere, it was possible to fabricate composites reinforced with SiCp. Reaction product (Al 4 C 3 ) was formed at the interface between SiCp and Al alloy matrix. In addition, the amount and size of the Al 4 C 3 is increased significantly by increasing the infiltration temperature. The reaction product (AlN) was formed as a result of the in situ reaction in both the control alloy and the composite. A significant strengthening even in the control alloy occurred due to the formation of in situ AIN particle even without an addition of SiCp. While a further strengthening of the composite was produced by the reinforced SiCp, strain to failure of the composite fabricated at 800 °C showed the lowest value (1.3%) in the T6 condition due to the formation of the severe reaction product (Al 4 C 3 ). The grain size of the control alloy significantly decreased to about 20 μm compared to 50 μm for the commercial alloy. In addition, the grain size in the composite reinforced with SiCp further decreased to about 8.0 μm. This grain refinement contributed to strengthening of the control alloy and composite.

A recurring problem with cancer therapies is the development of drug resistance. While investigating the protein profile of cells resistant to a novel antimitotic compound (A204197), we discovered an increase in annexin IV expression. When we examined the annexin IV protein expression level in a paclitaxel-resistant cell line (H460/T800), we found that annexin IV was also overexpressed. Interestingly a closely related protein, annexin II, was not overexpressed in H460/T800 cells. Immunostaining with either annexin II or IV antibody revealed that annexin IV was primarily located in the nucleus of paclitaxel-resistant H460/T800 cells. Short-term treatment of H460 cells with 10 nMpaclitaxel for up to 4 days resulted in induction of annexin IV, but not annexin II expression. In addition, there was an increase in annexin IV staining in the nucleus starting at day 1. Furthermore, cells pretreated with 10 nMpaclitaxel for 4 days resulted in cells becoming ~fivefold more resistant to paclitaxel. Transfection of annexin IV cDNA into 293T cells revealed that there was a threefold increase in paclitaxel resistance. Thus our results indicate that annexin IV plays a role in paclitaxel resistance in this cell line and it is among one of the earliest proteins that is induced in cells in response to cytotoxic stress such as antimitotic drug treatment. © 2000 Cancer Research Campaign