Intravitreal ranibizumab and bevacizumab in combination with full-fluence verteporfin therapy and dexamethasone for exudative age-related macular degeneration.

Abstract PURPOSE: To evaluate the efficacy and safety of triple therapy with intravitreal anti-vascular-endothelial-growth-factor (VEGF) antibody, dexamethasone and verteporfin photodynamic therapy (PDT) for exudative age-related macular degeneration (AMD). METHODS: Retrospective, comparative, interventional study. Records of treatment-naïve patients who received intravitreal bevacizumab or ranibizumab in monotherapy or in combination with dexamethasone and full-fluence verteporfin PDT in triple therapy were reviewed. logMAR visual acuity, foveal thickness (FT) on optical coherence tomography, intraocular pressure and endophthalmitis occurrence were recorded. RESULTS: Sixty-one eyes were included in the triple-therapy group, 40 eyes were included in the monotherapy group. The mean follow-up was 14.1 ± 3.4 months in the triple-therapy group and 16.3 ± 4.1 months in the monotherapy group. The triple-therapy group enjoyed a lower total number of treatments (1.92 ± 0.44 vs. 3.12 ± 0.37, p < 0.001) and a longer time before first retreatment (5.4 ± 3.3 vs. 3.6 ± 2.5 months, p = 0.001). A significant improvement of visual acuity and FT was present in both groups during the 12 months following first treatment. No adverse effects were observed. CONCLUSION: The combination of intravitreal bevacizumab or ranibizumabwith dexamethasone and full-fluence PDT for exudative AMD provided visual and anatomic improvement and a good safety profile. Triple therapy may reduce the number of retreatments when compared to anti-VEGF alone

Cross Sectional and Longitudinal Associations between Cardiovascular Risk Factors and Age Related Macular Degeneration in the EPIC-Norfolk Eye Study.

PURPOSE: To examine the cross sectional and longitudinal relationship between cardiovascular risk factors and age-related macular degeneration (AMD) in a large British cohort study. METHODS: The EPIC Norfolk Eye study is nested in a larger prospective cohort study. Data on cardiovascular risk factors were collected at baseline (1993-1997) and follow up (2006-2011) via clinical examination, validated lifestyle questionnaires and serum blood samples. AMD was ascertained using standardised grading of fundus photographs at the follow up. Logistic regression was used to examine associations between baseline and follow up risk factors with AMD. RESULTS: 5,344 pairs (62.0% of total 8623) of fundus photographs were of sufficient quality for grading of AMD in participants with mean age of 67.4 years old (range 44-91) at diagnosis. There were 28 cases of late AMD (0.5%, 95% confidence interval (CI)=0.3-0.8%) and 645 cases of early AMD (12.1%, 95%CI=11.2-13.0.%). In multivariable analysis, older people with higher levels of baseline high density lipoprotein- cholesterol (HDL-C ) and C-reactive protein (CRP) were more likely to have any signs of AMD, after adjusting for sex, education, smoking, and systolic blood pressure. In cross sectional analysis, only older age and higher HDL were significantly associated with AMD. CONCLUSIONS: We have found that older age and higher levels of CRP and HDL-C were associated with increased odds of AMD in this population in the longitudinal analysis, but older age and HDL-C, not CRP was significantly associated with AMD in the cross sectional analysis. The prevalence of AMD in this cohort was low compared to other cohorts in Europe, the US and Australia, and probably reflects the some selection biases in follow up participation as well as the low rate of smoking among our healthy participants.EPIC-Norfolk infrastructure and core functions are supported by grants from the Medical Research Council (G0401527) and Cancer Research UK (C864/A8257). The clinic for the third health examination was funded by Age UK Research into Ageing grant (262). Dr Yip is a National Institute for Health Research (NIHR) Clinical Lecturer. Dr Khawaja is a Wellcome Trust Clinical Research Fellow. Michelle Chan is an MRC/RCOphth Clinical Training Fellow and has received additional support from the International Glaucoma Association. Professor Foster has received additional support from the Richard Desmond Charitable Trust (via Fight for Sight). Professor Foster and Tunde Peto received funding from the Department for Health through the award made by the NIHR to Moorfields Eye Hospital and the UCL Institute of Ophthalmology for a specialist Biomedical Research Centre for Ophthalmology.This is the final version of the article. It first appeared from PLoS via http://dx.doi.org/10.1371/journal.pone.013256

Control and Characterization of Individual Grains and Grain Boundaries in Graphene Grown by Chemical Vapor Deposition

The strong interest in graphene has motivated the scalable production of high quality graphene and graphene devices. Since large-scale graphene films synthesized to date are typically polycrystalline, it is important to characterize and control grain boundaries, generally believed to degrade graphene quality. Here we study single-crystal graphene grains synthesized by ambient CVD on polycrystalline Cu, and show how individual boundaries between coalescing grains affect graphene's electronic properties. The graphene grains show no definite epitaxial relationship with the Cu substrate, and can cross Cu grain boundaries. The edges of these grains are found to be predominantly parallel to zigzag directions. We show that grain boundaries give a significant Raman "D" peak, impede electrical transport, and induce prominent weak localization indicative of intervalley scattering in graphene. Finally, we demonstrate an approach using pre-patterned growth seeds to control graphene nucleation, opening a route towards scalable fabrication of single-crystal graphene devices without grain boundaries.Comment: New version with additional data. Accepted by Nature Material

The first determination of Generalized Polarizabilities of the proton by a Virtual Compton Scattering experiment

Absolute differential cross sections for the reaction (e+p -> e+p+gamma) have been measured at a four-momentum transfer with virtuality Q^2=0.33 GeV^2 and polarization \epsilon = 0.62 in the range 33.6 to 111.5 MeV/c for the momentum of the outgoing photon in the photon-proton center of mass frame. The experiment has been performed with the high resolution spectrometers at the Mainz Microtron MAMI. From the photon angular distributions, two structure functions which are a linear combination of the generalized polarizabilities have been determined for the first time.Comment: 4 pages, 3 figure

Toll-like receptor polymorphisms and cerebral malaria: <it>TLR2 </it>Δ22 polymorphism is associated with protection from cerebral malaria in a case control study

<p>Abstract</p> <p>Background</p> <p>In malaria endemic areas, host genetics influence whether a <it>Plasmodium falciparum</it>-infected child develops uncomplicated or severe malaria. TLR2 has been identified as a receptor for <it>P. falciparum</it>-derived glycosylphosphatidylinositol (GPI), and polymorphisms within the TLR2 gene may affect disease pathogenesis. There are two common polymorphisms in the 5' un-translated region (UTR) of TLR2, a 22 base pair deletion in the first unstranslated exon (Δ22), and a GT dinucleotide repeat in the second intron (GTn).</p> <p>Methods</p> <p>These polymorphisms were examined in a Ugandan case control study on children with either cerebral malaria or uncomplicated malaria. Serum cytokine levels were analysed by ELISA, according to genotype and disease status. In vitro TLR2 expression was measured according to genotype.</p> <p>Results</p> <p>Both Δ22 and GTn polymorphisms were highly frequent, but only Δ22 heterozygosity was associated with protection from cerebral malaria (OR 0.34, 95% confidence intervals 0.16, 0.73). In vitro, heterozygosity for Δ22 was associated with reduced pam3cys inducible TLR2 expression in human monocyte derived macrophages. In uncomplicated malaria patients, Δ22 homozygosity was associated with elevated serum IL-6 (<it>p </it>= 0.04), and long GT repeat alleles were associated with elevated TNF (<it>p </it>= 0.007).</p> <p>Conclusion</p> <p>Reduced inducible TLR2 expression may lead to attenuated pro-inflammatory responses, a potential mechanism of protection from cerebral malaria present in individuals heterozygous for the TLR2 Δ22 polymorphism.</p

From tension to compression: Asymmetric mechanical behaviour of trabecular bone's organic phase

Trabecular bone is a cellular composite material comprising primarily of mineral and organic phases with their content ratio known to change with age. Therefore, the contribution of bone constituents on bone’s mechanical behaviour, in tension and compression, at varying load levels and with changing porosity (which increases with age) is of great interest, but remains unknown. We investigated the mechanical response of demineralised bone by subjecting a set of bone samples to fully reversed cyclic tension–compression loads with varying magnitudes. We show that the tension to compression response of the organic phase of trabecular bone is asymmetric; it stiffens in tension and undergoes stiffness reduction in compression. Our results indicate that demineralised trabecular bone struts experience inelastic buckling under compression which causes irreversible damage, while irreversible strains due to microcracking are less visible in tension. We also identified that the values of this asymmetric mechanical response is associated to the original bone volume ratio (BV/TV)

The Enterovirus 71 A-particle Forms a Gateway to Allow Genome Release: A CryoEM Study of Picornavirus Uncoating

Since its discovery in 1969, enterovirus 71 (EV71) has emerged as a serious worldwide health threat. This human pathogen of the picornavirus family causes hand, foot, and mouth disease, and also has the capacity to invade the central nervous system to cause severe disease and death. Upon binding to a host receptor on the cell surface, the virus begins a two-step uncoating process, first forming an expanded, altered "A-particle", which is primed for genome release. In a second step after endocytosis, an unknown trigger leads to RNA expulsion, generating an intact, empty capsid. Cryo-electron microscopy reconstructions of these two capsid states provide insight into the mechanics of genome release. The EV71 A-particle capsid interacts with the genome near the icosahedral two-fold axis of symmetry, which opens to the external environment via a channel ~10 Å in diameter that is lined with patches of negatively charged residues. After the EV71 genome has been released, the two-fold channel shrinks, though the overall capsid dimensions are conserved. These structural characteristics identify the two-fold channel as the site where a gateway forms and regulates the process of genome release. © 2013 Shingler et al

Bone marrow stromal cells attenuate sepsis via prostaglandin E2— dependent reprogramming of host macrophages to increase their interleukin-10 production

Sepsis causes over 200,000 deaths yearly in the US; better treatments are urgently needed. Administering bone marrow stromal cells (BMSCs—also known as mesenchymal stem cells) to mice before or shortly after inducing sepsis by cecal ligation and puncture reduced mortality and improved organ function. The beneficial effect of BMSCs was eliminated by macrophage depletion or pretreatment with antibodies specific for interleukin-10 (IL-10) or IL-10 receptor. Monocytes and/ or macrophages from septic lungs made more IL-10 when prepared from mice treated with BMSCs versus untreated mice. Lipopolysaccharide (LPS)-stimulated macrophages produced more IL-10 when cultured with BMSCs, but this effect was eliminated if the BMSCs lacked the genes encoding Toll-like receptor 4, myeloid differentiation primary response gene-88, tumor necrosis factor (TNF) receptor-1a or cyclooxygenase-2. Our results suggest that BMSCs (activated by LPS or TNF-α) reprogram macrophages by releasing prostaglandin E2 that acts on the macrophages through the prostaglandin EP2 and EP4 receptors. Because BMSCs have been successfully given to humans and can easily be cultured and might be used without human leukocyte antigen matching, we suggest that cultured, banked human BMSCs may be effective in treating sepsis in high-risk patient groups.Sepsis, a serious medical condition that affects 18 million people per year worldwide, is characterized by a generalized inflammatory state caused by infection. Widespread activation of inflammation and coagulation pathways progresses to multiple organ dysfunction, collapse of the circulatory system (septic shock) and death. Because as many people die of sepsis annually as from acute myocardial infarction1, a new treatment regimen is desperately needed. In the last few years, it has been discovered that BMSCs are potent modulators of immune responses2-5. We wondered whether such cells could bring the immune response back into balance, thus attenuating the underlying pathophysiology that eventually leads to severe sepsis, septic shock and death6,7. As a model of sepsis, we chose cecal ligation and puncture (CLP), a procedure that has been used for more than two decades8. This mouse model closely resembles the human disease: it has a focal origin (cecum), is caused by multiple intestinal organisms, and results in septicemia with release of bacterial toxins into the circulation. With no treatment, the majority of the mice die 24-48 h postoperatively. Originally published Nature Medicine, Vol. 15, No. 1, Jan 200

Photography-based taxonomy is inadequate, unnecessary, and potentially harmful for biological sciences

The question whether taxonomic descriptions naming new animal species without type specimen(s) deposited in collections should be accepted for publication by scientific journals and allowed by the Code has already been discussed in Zootaxa (Dubois & Nemésio 2007; Donegan 2008, 2009; Nemésio 2009a–b; Dubois 2009; Gentile & Snell 2009; Minelli 2009; Cianferoni & Bartolozzi 2016; Amorim et al. 2016). This question was again raised in a letter supported by 35 signatories published in the journal Nature (Pape et al. 2016) on 15 September 2016. On 25 September 2016, the following rebuttal (strictly limited to 300 words as per the editorial rules of Nature) was submitted to Nature, which on 18 October 2016 refused to publish it. As we think this problem is a very important one for zoological taxonomy, this text is published here exactly as submitted to Nature, followed by the list of the 493 taxonomists and collection-based researchers who signed it in the short time span from 20 September to 6 October 2016