Treatment of optic neuritis with erythropoietin (TONE): a randomised, double-blind, placebo-controlled trial-study protocol.

INTRODUCTION Optic neuritis leads to degeneration of retinal ganglion cells whose axons form the optic nerve. The standard treatment is a methylprednisolone pulse therapy. This treatment slightly shortens the time of recovery but does not prevent neurodegeneration and persistent visual impairment. In a phase II trial performed in preparation of this study, we have shown that erythropoietin protects global retinal nerve fibre layer thickness (RNFLT-G) in acute optic neuritis; however, the preparatory trial was not powered to show effects on visual function. METHODS AND ANALYSIS Treatment of Optic Neuritis with Erythropoietin (TONE) is a national, randomised, double-blind, placebo-controlled, multicentre trial with two parallel arms. The primary objective is to determine the efficacy of erythropoietin compared to placebo given add-on to methylprednisolone as assessed by measurements of RNFLT-G and low-contrast visual acuity in the affected eye 6 months after randomisation. Inclusion criteria are a first episode of optic neuritis with decreased visual acuity to ≤0.5 (decimal system) and an onset of symptoms within 10 days prior to inclusion. The most important exclusion criteria are history of optic neuritis or multiple sclerosis or any ocular disease (affected or non-affected eye), significant hyperopia, myopia or astigmatism, elevated blood pressure, thrombotic events or malignancy. After randomisation, patients either receive 33 000 international units human recombinant erythropoietin intravenously for 3 consecutive days or placebo (0.9% saline) administered intravenously. With an estimated power of 80%, the calculated sample size is 100 patients. The trial started in September 2014 with a planned recruitment period of 30 months. ETHICS AND DISSEMINATION TONE has been approved by the Central Ethics Commission in Freiburg (194/14) and the German Federal Institute for Drugs and Medical Devices (61-3910-4039831). It complies with the Declaration of Helsinki, local laws and ICH-GCP. TRIAL REGISTRATION NUMBER NCT01962571.

Comparison of health behaviors of Mexican American and non -Hispanic White females: Implications for health promotion programs

Hispanics form the second-largest minority group in the United States totaling 22 million people. Health data on this population are sparse and inconsistent. This study seeks to determine use of preventative services and risk factor behaviors of Mexican American and non-Hispanic White females residing in South Texas.^ Baseline data from female respondents in household surveys in six South Texas counties (Ramirez and McAlister, 1988; McAlister et al., 1992) were analyzed to test the following hypotheses: (1) Mexican American and Non-Hispanic White females exhibit different patterns of health behaviors; (2) Mexican American females will exhibit different health behaviors regardless of age; and (3) the differences between Mexican American women and non-Hispanic White females are due to education and acculturation factors.^ Over the past decade, the traditional behaviors of Mexican American females have begun to change due to education, acculturation, and their participation in the labor force. The results from this study identify some of the changes that will require immediate attention from health care providers. Results revealed that regardless of ethnicity, age, education, and language preference, non-Hispanic White females were significantly more likely to participate in preventive screening practices than were Mexican American females. Risk factor analysis revealed a different pattern with Mexican American females significantly more likely to be non-smokers, non-alcoholic drinkers, and to have good fat avoidance practices compared to non-Hispanic White females. However, compared to those who are less-educated or Spanish-speaking, Mexican American females with higher levels of education and preference for speaking English only showed positive and negative health behaviors that were more similar to the non-Hispanic White females. The positive health behaviors that come with acculturation, e.g., more participation in preventive care and more physical activity, are welcome changes. But this study has implications for global health development and reinforces a need for "primordial" prevention strategies to deter the unwanted concomitants of economic development and acculturation. Smoking and drinking behaviors among Mexican American females need to be kept at low levels to prevent increased morbidity and premature deaths in this population. ^

Sedimentological and clay mineralogical analysis of ODP sites in the central Fram Strait

This study presents the results of high-resolution sedimentological and clay mineralogical investigations on sediments from ODP Sites 908A and 909AlC located in the central Fram Strait. The objective was to reconstruct the paleoclimate and paleoceanography of the high northern latitudes since the middle Miocene. The sediments are characterised in particular by a distinctive input of ice-rafted material, which most probably occurs since 6 Ma and very likely since 15 Ma. A change in the source area at 1 1.2 Ma is clearly marked by variations within clay mineral composition and increasing accumulation rates. This is interpreted as a result of an increase in water mass exchange through the Fram Strait. A further period of increasing exchange between 4-3 Ma is identified by granulometric investigations and points to a synchronous intensification of deep water production in the North Atlantic during this time interval. A comparison of the components of coarse and clay fraction clearly shows that both are not delivered by the Same transport process. The input of the clay fraction can be related to transport mechanisms through sea ice and glaciers and very likely also through oceanic currents. A reconstruction of source areas for clay minerals is possible only with some restrictions. High smectite contents in middle and late Miocene sediments indicate a background signal produced by soil formation together with sediment input, possibly originating from the Greenland- Scotland Ridge. The applicability of clay mineral distribution as a climate proxy for the high northern latitudes can be confirmed. Based on a comparison of sediments from Site 909C, characterised by the smectite/illite and chlorite ratio, with regional and global climatic records (oxygen isotopes), a middle Miocene cooling phase between 14.8-14.6 Ma can be proposed. A further cooling phase between 10-9 Ma clearly shows similarities in its Progress toward drastic decrease in carbonate sedimentation and preservation in the eastern equatorial Pacific. The modification in sea water and atmosphere chemistry may represent a possible link due to the built-up of equatorial carbonate platforms. Between 4.8-4.6 Ma clay mineral distribution indicates a distinct cooling trend in the Fram Strait region. This is not accompanied by relevant glaciation, which would otherwise be indicated by the coarse fraction. The intensification of glaciation in the northern hemisphere is distinctly documented by a rapid increase of illite and chlorite starting from 3.3 Ma, which corresponds to oxygen isotope data trends from North Atlantic.

Accumulation rate, carbon geochemistry and clay mineralogy of ODP Site 181-1123 sediments, southwest Pacific

Site 1123 is located on the northeastern flank of the Chatham Rise. Sedimentological and clay mineralogical analyses indicate a very fine grained carbonate-rich sediment. Smectite and illite are the main constituents of the clay mineral assemblage. High smectite values in the Eocene decrease in younger sediment sequences. Illite and chlorite concentrations increase in younger sediments with significant steps at 13.5, 9, and 6.4 Ma. The kaolinite content is near the detection limit and not significant. We observed only small fluctuations of the clay mineral composition, which indicates a uniform sedimentation process, probably driven by long-term processes. Good correspondence is shown between increasing illite and chlorite values and the tectonic uplift history of the Southern Alps.

Age determination and planktonic foraminifera og ODP Site 159-958

Site 958 was drilled to monitor the late Neogene history of both continental aridity in northwestern Africa and the Canary Current distant from nearshore upwelling. Based on magnetostratigraphy, biostratigraphic datums, variations in carbonate, coarse fraction components, and the species composition of planktonic foraminifers, as well as using the d18O records of Globigerinoides ruber (white), we established a splice between Holes 958A and 958B and a stratigraphic age scale deciphering Milankovitch cycles. Over the last 630 k.y., sedimentation rates amount to 2.9 cm/k.y., and to 2.05-2.53 cm/k.y. back to the base of the Pleistocene. Extremely low rates of 0.4 cm/k.y. and a reworking of fossils mark the late Pliocene. The first continuous, long, sea-surface temperature (SST) record from the center of the Canary Current, which is based on foraminifer species census data, depicts a general temperature decrease in the late Pliocene, lower SST and high seasonalities of up to 6°C ~2.0-1.6 Ma, a warmer interval from 1.6 Ma to ~0.85 Ma, again lower SST and higher seasonalities until 0.33 or 0.26 Ma, and a final warmer interval, lasting until at least 50 ka, possibly reflecting the attenuated dynamics of the Canary Current. Especially over the last 400 k.y., since Stage 11, glacial stages are hardly reflected by cold SST cycles, except for various abrupt and extremely short cooling events amounting to D6°C, which possibly result from North Atlantic Heinrich events. Similar, but not necessarily synchronous, events of short-term, extremely high values occur in the paleoproductivity and (d13Cbased) paleonutrient records, which indicate a generally low primary production averaging to 180 g C m**-2 yr**-1 at 50-330 ka and about 300 g C m**-2 yr**-1 back to the base of the Pleistocene. Near 1.2-1.6 Ma, the grain-size and magnetic susceptibility records document a significant increase in the discharge of south Saharan/Sahelian dust, possibly linked to increasing aridity.