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This study compared the general and ocular biometric characteristics of normal, primary angle closure (PAC), and primary angle-closure glaucoma (PACG) patients to better understand the possible relationship between differences in ocular parameters that might predict risk for PACG in PAC patients. One hundred normal, 90 PAC, and 90 PACG eyes were retrospectively reviewed. General characteristics such as age, gender, body height, body weight, blood pressure, pulse, systemic diseases, and education level were recorded. Ocular findings included visual acuity, intraocular pressure, refraction, cup to disc ratio, and ocular biometry. Ocular biometry was obtained by A-scan ultrasonography (Digital A/B scan 5500; Sonomed Inc., Lake Success, NY, USA). The parameters recorded were anterior chamber depth (ACD), lens thickness (LT), axial length (AXL), lens/axial length factor (LAF), and relative lens position (RLP). Although the controls, PAC group, and PACG group were found to be significantly different in age (62.7±9.8; 65.3±7.5; and 66.0±7.4, respectively), there were no gender differences. With regard to ocular parameters, the ACD tended to decrease and the LT and LAF tended to increase from normal to PAC to PACG. The eyes of the PACG group had significantly shallower ACD (P

The low hilly topography of Green Island, a volcanic island off southeastern Taiwan, includes an altitudinal sequence of sub-horizontal benches. We examined eight profiles along this sequence, ranging from pale brown loamy coral sand on the lowest bench that fringes the coast at an elevation of about 10 m to deep, intensely red and acid clay on the highest bench at about 240 m. Chemical analyses, differential Fe extractions, thin sections, X-ray diffraction of the clay minerals and indices of pedochemical weathering and strain indicated that soil development progressed by weathering of primary and secondary phyllosilicates through argilluviation in the intermediate stages to the generation of increasing quantities of free Fe. The Fe accumulates as free sesquioxides, which crystallize with age. Taxonomically the soil types progress from sandy coral Arenosol, through Eutric Cambisol, Hypereutric Lixisol and Acrisol to incipient Ferralsol (Udipsamment → Eutrudept → Udalf → Udultisol → Udox in Soil Taxonomy). The profiles are interpreted as a chronosequence, although this is complicated by minor and upwardly diminishing contributions of reef coral to the mainly igneous parent materials. There are also variations in the andesitic-basaltic bedrock, and minor aeolian inputs in the higher and older soil types. Regional eustatic sea-level correlations, 14C dating of carbonates on the two lowest benches and estimates of local tectonic uplift indicate that the incipient Ferralsols on the upper bench might date from about 150 ka. The transition through argilluvial Acrisols to incipient sesquioxide-dominated Ferralsols appears, therefore, to develop within 100–200 ka on Green Island, which is faster than usual.

Source: ICHE Conference Archive - https://mdi-de.baw.de/icheArchive/

Effective systemic therapies for patients with advanced, progressive neuroendocrine tumours of the lung or gastrointestinal tract are scarce. We aimed to assess the efficacy and safety of everolimus compared with placebo in this patient population.In the randomised, double-blind, placebo-controlled, phase 3 RADIANT-4 trial, adult patients (aged ≥18 years) with advanced, progressive, well-differentiated, non-functional neuroendocrine tumours of lung or gastrointestinal origin were enrolled from 97 centres in 25 countries worldwide. Eligible patients were randomly assigned in a 2:1 ratio by an interactive voice response system to receive everolimus 10 mg per day orally or identical placebo, both with supportive care. Patients were stratified by tumour origin, performance status, and previous somatostatin analogue treatment. Patients, investigators, and the study sponsor were masked to treatment assignment. The primary endpoint was progression-free survival assessed by central radiology review, analysed by intention to treat. Overall survival was a key secondary endpoint. This trial is registered with ClinicalTrials.gov, number NCT01524783.Between April 3, 2012, and Aug 23, 2013, a total of 302 patients were enrolled, of whom 205 were allocated to everolimus 10 mg per day and 97 to placebo. Median progression-free survival was 11·0 months (95% CI 9·2-13·3) in the everolimus group and 3·9 months (3·6-7·4) in the placebo group. Everolimus was associated with a 52% reduction in the estimated risk of progression or death (hazard ratio [HR] 0·48 [95% CI 0·35-0·67], p0·00001). Although not statistically significant, the results of the first pre-planned interim overall survival analysis indicated that everolimus might be associated with a reduction in the risk of death (HR 0·64 [95% CI 0·40-1·05], one-sided p=0·037, whereas the boundary for statistical significance was 0·0002). Grade 3 or 4 drug-related adverse events were infrequent and included stomatitis (in 18 [9%] of 202 patients in the everolimus group vs 0 of 98 in the placebo group), diarrhoea (15 [7%] vs 2 [2%]), infections (14 [7%] vs 0), anaemia (8 [4%] vs 1 [1%]), fatigue (7 [3%] vs 1 [1%]), and hyperglycaemia (7 [3%] vs 0).Treatment with everolimus was associated with significant improvement in progression-free survival in patients with progressive lung or gastrointestinal neuroendocrine tumours. The safety findings were consistent with the known side-effect profile of everolimus. Everolimus is the first targeted agent to show robust anti-tumour activity with acceptable tolerability across a broad range of neuroendocrine tumours, including those arising from the pancreas, lung, and gastrointestinal tract.Novartis Pharmaceuticals Corporation.

The present investigation was carried out to evaluate the effect of greater immunomodulatory effects of human peripheral blood mononuclear cells against proliferation in human leukemia cells. To achieve this, cells U937 in junior elderly (with cool environmental physical activities) subjects with habitual morning swimming and sedentary lifestyle were recruited in relatively cool season in Taiwan; the isolated human peripheral blood mononuclear cells were stimulated by phytohemagglutinin to obtain the conditioned medium which contains various cytokines. However, the differential effects of the conditioned medium on growth inhibition in U937 leukemia cells were observed. The cytokines, including interferon-gamma, tumor necrosis factors-alpha and interleukine-2 secreted into conditioned medium were higher in the morning-swimming subjects than in the sedentary-lifestyle ones. Similarly, serum white blood cell, creatine phosphokinase, immunoglobulin G and immunoglobulin A in the morning-swimming and sedentary-lifestyle groups indicated that no further inflammatory status existed in the morning-swimming group. In summary, greater immunomodulatory effects of human peripheral blood mononuclear cells against proliferation in human leukemia cells U937 in junior elderly subjects came from the effects of regular moderate exercise in cool temperature rather than of inflammatory effects.Keywords: Immunomodulatory, junior elderly, morning swimming, leukemia, U937, human peripheral blood mononuclear cells

We report on the ineffectiveness of programming oxide-based resistive random access memory (OxRAM) at low current with a program and verify algorithm due to intrinsic relaxation of the verified distribution to the natural state distribution obtained by single-pulse programming without verify process. Based on oxygen defect formation thermodynamics and on their diffusion barriers in amorphous HfOx and TaOx, we describe the intrinsic nature of tailing of the verified low resistive state and high resistive state distributions. We introduce different scenarios to explain fast distribution widening phenomenon, which is a fundamental limitation for OxRAM current scaling and device reliability.

The binding of vascular endothelial growth factor (VEGF) to VEGF receptor-2 (VEGFR-2) on the surface of vascular endothelial cells stimulates many steps in the angiogenic pathway. Inhibition of this interaction is proving of value in moderating the neovascularization accompanying age-related macular degeneration and in the treatment of cancer. Tissue inhibitor of metalloproteinases-3 (TIMP-3) has been shown to be a natural VEGFR-2 specific antagonist—an activity that is independent of its ability to inhibit metalloproteinases. In this investigation we localize this activity to the C-terminal domain of the TIMP-3 molecule and characterize a short peptide, corresponding to part of this domain, that not only inhibits all three VEGF-family receptors, but also fibroblast growth factor and platelet-derived growth factor receptors. This multiple-receptor inhibition may explain why the peptide was also seen to be a powerful inhibitor of tumour growth and also a partial inhibitor of arthritic joint inflammation in vivo.

Several spirocyclic piperidine derivatives were designed and synthesized as σ1 receptor ligands. In vitro competition binding assays showed that the fluoroalkoxy analogues with small substituents possessed high affinity towards σ1 receptors and subtype selectivity. Particularly for ligand 1'-((6-(2-fluoro-ethoxy)pyridin-3-yl)methyl)-3H-spiro[2-benzofuran-1,4'-piperidine] (2), high σ1 receptor affinity (Ki = 2.30 nM) and high σ1/σ2 subtype selectivity (142-fold) as well as high σ1/VAChT selectivity (234-fold) were observed. [18F]2 was synthesized using an efficient one-pot, two-step reaction method in a home-made automated synthesis module, with an overall isolated radiochemical yield of 8-10%, a radiochemical purity of higher than 99%, and specific activity of 56-78 GBq/µmol. Biodistribution studies of [18F]2 in ICR mice indicated high initial brain uptake and a relatively fast washout. Administration of haloperidol, compound 1 and different concentrations of SA4503 (3, 5, or 10 µmol/kg) 5 min prior to injection of [18F]2 significantly decreased the accumulation of radiotracer in organs known to contain σ1 receptors. Ex vivo autoradiography in Sprague-Dawley rats demonstrated high accumulation of radiotracer in brain areas with high expression of σ1 receptors. These encouraging results prove that [18F]2 is a suitable candidate for σ1 receptor imaging with PET in humans.

Background: We have previously reported in Xishuangbanna (Banna) Dai Autonomous Prefecture, a well-developed tourist destination in the southwest border of China, that HIV-1 transmitted dominantly through heterosexual contact with less divergent genotypes and few drug resistant mutations [1]. Due to the rapid increase of newly diagnosed HIV-1 cases per year in Banna in recent years, it's important to evaluate the evolution of HIV-1 molecular epidemiology for the better understanding of ongoing HIV-1 outbreak in this region. Methodology/Principal Findings: By sequencing of HIV-1 pol genes and phylogenetic analysis, we conducted a molecular epidemiologic study in 352 HIV-1-seropositive highly active antiretroviral treatment (HAART)-naive individuals newly diagnosed at the Banna Center for Disease Control and Prevention between 2009 and 2011. Of 283 samples (84.1% taken from heterosexually acquired adults, 10.6% from needle-sharing drug users, 2.8% from men who have sex with men, 0.4% from children born from HIV-1-infected mothers, and 2.1% remained unknown) with successful sequencing for pol gene, we identified 108 (38.2%) HIV-1 subtype CRF08_BC, 101 (35.7%) CRF01_AE, 49 (17.3%) CRF07_BC, 5 (1.8%) C/CRF57_BC, 3 (1.1%) B', 1 (0.4%) B/CRF51_01B, and 16 (5.7%) unique recombinants forms. Among these infected individuals, 104 (36.7%) cases showed drug resistant or resistance-relevant mutations, and 4 of them conferring high-level resistance to 3TC/FTC, EFV/NVP or NFV. Phylogenetic analysis revealed 21 clusters (2-7 sequences) with only 21.2% (60/283) sequences involved. Conclusion/Significance: In contrast to our previous findings, CRF08_BC, replaced CRF01_AE, became the dominant genotype of HIV-1 in Banna prefecture. The viral strains with drug resistance mutations were detected frequently in newly diagnosed HIV-1-infected individuals in this region.