Same-day administration of verteporfin and ranibizumab 0.5 mg in patients with choroidal neovascularisation due to age-related macular degeneration

OBJECTIVE: To evaluate safety of same-day administration of verteporfin and ranibizumab. METHODS: Prospective, open-label, multicentre study; patients with predominantly classic (n = 13) or occult (n = 19) choroidal neovascularisation secondary to age-related macular degeneration received standard-fluence verteporfin at baseline and months 3, 6 and 9, based on fluorescein angiography (FA). Ranibizumab 0.5 mg was administered at baseline and months 1, 2 and 3. MAIN OUTCOME MEASURE: The incidence of severe vision loss (best-corrected visual acuity (BCVA) loss > or = 30 letters; primary safety assessment). RESULTS: No severe vision loss due to ocular inflammation or uveitis occurred. One patient had moderate vision loss (BCVA loss > or = 15 letters). Three patients had mild/moderate uveitis. Two serious ocular adverse events occurred (retinal pigment epithelial tear and moderate BCVA decrease). No systemic adverse events occurred. At 9 months, all lesions were inactive with no recurrent leakage on FA and optical coherence tomography; macular oedema and subretinal fluid resolved. The mean BCVA measured at 2 m improved by 6.9 letters at 4 months and 2.4 letters at 9 months. CONCLUSIONS/APPLICATION TO CLINICAL PRACTICE: Same-day verteporfin and ranibizumab was safe and not associated with severe vision loss or severe ocular inflammation. Lesions stabilized, with minimal treatment required after month 3.

Effect of once-yearly zoledronic acid 5 mg on fracture risk and change in femoral neck bone mineral density

Context: In the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly - Pivotal Fracture Trial (HORIZON-PFT), zoledronic acid (ZOL) 5 mg significantly reduced fracture risk. Objective: To identify factors associated with greater efficacy during ZOL 5 mg treatment. Design, Setting and Patients: Subgroup analysis (preplanned and post hoc) of a multicenter, double-blind, placebo-controlled, 36-month trial in 7765 women with postmenopausal osteoporosis. Intervention: Single infusion of ZOL 5 mg or placebo at baseline, 12 and 24 months. Main Outcome Measures: Primary endpoints: new vertebral fracture and hip fracture. Secondary endpoints: non-vertebral fracture, change in femoral neck bone mineral density (BMD). Baseline risk factor subgroups: age, BMD T-score and vertebral fracture status, total hip BMD, race, weight, geographical region, smoking, height loss, history of falls, physical activity, prior bisphosphonates, creatinine clearance, body mass index (BMI), concomitant osteoporosis medications. Results: Greater ZOL induced effects on vertebral fracture risk with younger age (treatment-by-subgroup interaction P=0.05), normal creatinine clearance (P=0.04), and BMI >/=25 kg/m(2) (P=0.02). There were no significant treatment-factor interactions for hip or non-vertebral fracture or for change in BMD. Conclusions: ZOL appeared more effective in preventing vertebral fracture in younger women, overweight/obese women and women with normal renal function. ZOL had similar effects irrespective of fracture risk factors or femoral neck BMD.

Rationale and design of a randomized, double-blind, parallel-group study of terutroban 30 mg/day versus aspirin 100 mg/day in stroke patients: the prevention of cerebrovascular and cardiovascular events of ischemic origin with terutroban in patients with a history of ischemic stroke or transient ischemic attack (PERFORM) study

BACKGROUND: Ischemic stroke is the leading cause of mortality worldwide and a major contributor to neurological disability and dementia. Terutroban is a specific TP receptor antagonist with antithrombotic, antivasoconstrictive, and antiatherosclerotic properties, which may be of interest for the secondary prevention of ischemic stroke. This article describes the rationale and design of the Prevention of cerebrovascular and cardiovascular Events of ischemic origin with teRutroban in patients with a history oF ischemic strOke or tRansient ischeMic Attack (PERFORM) Study, which aims to demonstrate the superiority of the efficacy of terutroban versus aspirin in secondary prevention of cerebrovascular and cardiovascular events. METHODS AND RESULTS: The PERFORM Study is a multicenter, randomized, double-blind, parallel-group study being carried out in 802 centers in 46 countries. The study population includes patients aged > or =55 years, having suffered an ischemic stroke (< or =3 months) or a transient ischemic attack (< or =8 days). Participants are randomly allocated to terutroban (30 mg/day) or aspirin (100 mg/day). The primary efficacy endpoint is a composite of ischemic stroke (fatal or nonfatal), myocardial infarction (fatal or nonfatal), or other vascular death (excluding hemorrhagic death of any origin). Safety is being evaluated by assessing hemorrhagic events. Follow-up is expected to last for 2-4 years. Assuming a relative risk reduction of 13%, the expected number of primary events is 2,340. To obtain statistical power of 90%, this requires inclusion of at least 18,000 patients in this event-driven trial. The first patient was randomized in February 2006. CONCLUSIONS: The PERFORM Study will explore the benefits and safety of terutroban in secondary cardiovascular prevention after a cerebral ischemic event.

Superspace description of wagnerite-group minerals (Mg,Fe,Mn) 2 (PO 4 )(F,OH)

Reinvestigation of more than 40 samples of minerals belonging to the wagnerite group (Mg, Fe, Mn)2(PO4)(F,OH) from diverse geological environments worldwide, using single-crystal X-ray diffraction analysis, showed that most crystals have incommensurate structures and, as such, are not adequately described with known polytype models (2b), (3b), (5b), (7b) and (9b). Therefore, we present here a unified superspace model for the structural description of periodically and aperiodically modulated wagnerite with the (3+1)-dimensional superspace group C2/c(0[beta]0)s0 based on the average triplite structure with cell parameters a [asymptotically equal to] 12.8, b [asymptotically equal to] 6.4, c [asymptotically equal to] 9.6 Å, [beta] [asymptotically equal to] 117° and the modulation vectors q = [beta]b*. The superspace approach provides a way of simple modelling of the positional and occupational modulation of Mg/Fe and F/OH in wagnerite. This allows direct comparison of crystal properties.

Atomistic Modeling of Effect of Mg on Oxygen Vacancy Diffusion in α-Alumina

Oxygen diffusion plays an important role in grain growth and densification during the sintering of alumina ceramics and governs high-temperature processes such as creep. The atomistic mechanism for oxygen diffusion in alumina is, however, still debated; atomistic calculations not being able to match experimentally determined activation energies for oxygen vacancy diffusion. These calculations are, however, usually performed for perfectly pure crystals, whereas virtually every experimental alumina sample contains a significant fraction of impurity/dopants ions. In this study, we use atomistic defect cluster and nudged elastic band (NEB) calculations to model the effect of Mg impurities/dopants on defect binding energies and migration barriers. We find that oxygen vacancies can form energetically favorable clusters with Mg, which reduces the number of mobile species and leads to an additional 1.5 eV energy barrier for the detachment of a single vacancy from Mg. The migration barriers of diffusive jumps change such that an enhanced concentration of oxygen vacancies is expected around Mg ions. Mg impurities were also found to cause destabilization of certain vacancy configurations as well as enhanced vacancy–vacancy interaction.

Variations of clinopyroxene/melt element partitioning during assimilation of olivine/peridotite by low-Mg diorite magma

The effects of crystal chemistry and melt composition on the control of clinopyroxene/melt element partitioning (D) during the assimilation of olivine/peridotite by felsic magma have been investigated in Mesozoic high-Mg diorites from North China. The assimilation resulted in significant increase of Mg, Cr and Ni and only slight (< 30%) decrease of incompatible elements of the magma, and the compositional variations have been mirrored by the normally and reversely zoned clinopyroxene microphenocrysts formed at the early stage of the magma evolution. The Mg# [100 × Mg / (Mg + Fe)] values of the reversely zoned clinopyroxenes increase from 65 to 75 in the core to 85–90 in the high-Mg midsection, and reduce back to 73–79 at the rim. Trace element profiles across all these clinopyroxene domains have been measured by LA-ICP-MS. The melt trace element composition has been constrained from bulk rock analyses of the fine-grained low- and high-Mg diorites. Clinopyroxene/melt partition coefficients for rare earth elements (REE) and Y in the high-Mg group zonings (Mg# > 73–79, DDy < 1.2) are positively correlated with tetrahedral IVAl and increase by a factor of 3–4 as tetrahedral IVAl increases from 0.01 to 0.1 per formula unit (pfu). These systematic variations are interpreted to be controlled by the clinopyroxene composition. In contrast, partition coefficients for low-Mg group zonings (Mg# < 75–79, DDy > 1.2) are elevated by up to an order of magnitude (for REE and Y) or more (for Zr and Hf) at similar IVAl, indicating dominant control of melt composition/structure. DZr and DHf show a larger sensitivity to the compositional change of crystal and melt than DREE. DTi values for the low- and high-Mg zonings show a uniform dependence on IVAl. DSr and DLi are insensitive to the compositional change of clinopyroxene and melt, resulting in Sr depletions in the clinopyroxene zonings with elevated REE without crystallization of plagioclase. Our observations show that crystal chemistry and melt composition/structure may alternatively control clinopyroxene/melt partitioning during the assimilation of peridotite by felsic magma, and may be useful for deciphering clinopyroxene compositions and related crust–mantle processes.

From stellar to planetary composition: Galactic chemical evolution of Mg/Si mineralogical ratio

Aims. The main goal of this work is to study element ratios that are important for the formation of planets of different masses. Methods. We study potential correlations between the existence of planetary companions and the relative elemental abundances of their host stars. We use a large sample of FGK-type dwarf stars for which precise Mg, Si, and Fe abundances have been derived using HARPS high-resolution and high-quality data. Results. A first analysis of the data suggests that low-mass planet host stars show higher [Mg/Si] ratios, while giant planet hosts present [Mg/Si] that is lower than field stars. However, we found that the [Mg/Si] ratio significantly depends on metallicity through Galactic chemical evolution. After removing the Galactic evolution trend only the difference in the [Mg/Si] elemental ratio between low-mass planet hosts and non-hosts was present in a significant way. These results suggest that low-mass planets are more prevalent around stars with high [Mg/Si]. Conclusions. Our results demonstrate the importance of Galactic chemical evolution and indicate that it may play an important role in the planetary internal structure and composition. The results also show that abundance ratios may be a very relevant issue for our understanding of planet formation and evolution.

Rast in der Wüste : (Gedicht)

Josefa Metz

Rast im Felde bei jüdischen Bauern in Dzygowka, Podolien [Illustration] : (Fotografie)

Scan von Monochrom-Mikroform