Live Attenuated Chimeric Yellow Fever Dengue Type 2 (Chimeri Vax -DEN2) Vaccine: Phase 1 clinical trial for safety and immunogenicity

A randomized double-blind Phase I Trial was conducted to evaluate safety, tolerability, and immunogenicity of a yellow fever (YF)-dengue 2 (DEN2) chimera (ChimeriVax™-DEN2) in comparison to that of YF vaccine (YF-VAX®). Forty-two healthy YF naïve adults randomly received a single dose of either ChimeriVax™-DEN2 (high dose, 5 log plaque forming units [PFU] or low dose, 3 log PFU) or YF-VAXâ by the subcutaneous route (SC). To determine the effect of YF pre-immunity on the ChimeriVaxTM-DEN2 vaccine, 14 subjects previously vaccinated against YF received a high dose of ChimeriVax™-DEN2 as an open-label vaccine. Most adverse events were similar to YF-VAX® and of mild to moderate intensity, with no serious side-effects. One hundred percent and 92.3% of YF naïve subjects inoculated with 5.0 and 3.0 log10 PFU of ChimeriVaxTM-DEN2, respectively, seroconverted to wt DEN2 (strain 16681); 92% of subjects inoculated with YF-VAX® seroconverted to YF 17D virus but none of YF naïve subjects inoculated with ChimeriVax-DEN2 seroconverted to YF 17D virus. Low seroconversion rates to heterologous DEN serotypes 1, 3, and 4 were observed in YF naïve subjects inoculated with either ChimeriVax™-DEN2 or YF-VAX®. In contrast, 100% of YF immune subjects inoculated with ChimeriVax™-DEN2 seroconverted to all 4 DEN serotypes. Surprisingly, levels of neutralizing antibodies to DEN 1, 2, and 3 viruses in YF immune subjects persisted after 1 year. These data demonstrated that 1) the safety and immunogenicity profile of the ChimeriVax™-DEN2 vaccine is consistent with that of YF-VAX®, and 2) pre-immunity to YF virus does not interfere with ChimeriVaxTM-DEN2 immunization, but induces a long lasting and cross neutralizing antibody response to all 4 DEN serotypes. The latter observation can have practical implications toward development of a dengue vaccine.

Mice lacking the vascular endothelial growth factor-B gene (Vegfb) have smaller hearts, dysfunctional coronary vasculature, and impaired recovery from cardiac ischemia

Vascular endothelial growth factor-B (VEGF-B) is closely related to VEGF-A, an effector of blood vessel growth during development and disease and a strong candidate for angiogenic therapies. To further study the in vivo function of VEGF-B, we have generated Vegfb knockout mice (Vegfb(-/-)). Unlike Vegfa knockout mice, which die during embryogenesis, Vegfb(-/-) mice are healthy and fertile. Despite appearing overtly normal, Vegfb(-/-) hearts are reduced in size and display vascular dysfunction after coronary occlusion and impaired recovery from experimentally induced myocardial ischemia. These findings reveal a role for VEGF-B in the development or function of coronary vasculature and suggest potential clinical use in therapeutic angiogenesis. The full text of this article is available at http://www.circresaha.org.

Induction of lipolysis in vitro and loss of body fat in vivo by zinc-alpha(2)-glycoprotein

Loss of adipose tissue in cancer cachexia has been associated with tumour production of a lipid-mobilizing factor (LMF) which has been shown to be homologous with the plasma protein zinc-a2-glycoprotein (ZAG). The aim of this study was to compare the ability of human ZAG with LMF to stimulate lipolysis in vitro and induce loss of body fat in vivo, and to determine the mechanisms involved. ZAG was purified from human plasma using a combination of Q Sepharose and Superdex 75 chromatography, and was shown to stimulate glycerol release from isolated murine epididymal adipocytes in a dose-dependent manner. The effect was enhanced by the cyclic AMP phosphodiesterase inhibitor Ro20-1724, and attenuated by freeze/thawing and the specific ß3-adrenoreceptor antagonist SR59230A. In vivo ZAG caused highly significant, time-dependent, decreases in body weight without a reduction in food and water intake. Body composition analysis showed that loss of body weight could be attributed entirely to the loss of body fat. Loss of adipose tissue may have been due to the lipolytic effect of ZAG coupled with an increase in energy expenditure, since there was a dose-dependent increase in expression of uncoupling protein-1 (UCP-1) in brown adipose tissue. These results suggest that ZAG may be effective in the treatment of obesity.

(Table 2) Radiocarbon dates from lakes on Fildes Peninsula, King George Island

Precise relative sea level (RSL) data are important for inferring regional ice sheet histories, as well as helping to validate numerical models of ice sheet evolution and glacial isostatic adjustment. Here we develop a new RSL curve for Fildes Peninsula, South Shetland Islands (SSIs), a sub-Antarctic archipelago peripheral to the northern Antarctic Peninsula ice sheet, by integrating sedimentary evidence from isolation basins with geomorphological evidence from raised beaches. This combined approach yields not only a Holocene RSL curve, but also the spatial pattern of how RSL change varied across the archipelago. The curve shows a mid-Holocene RSL highstand on Fildes Peninsula at 15.5 m above mean sea level between 8000 and 7000 cal a BP. Subsequently RSL gradually fell as a consequence of isostatic uplift in response to regional deglaciation. We propose that isostatic uplift occurred at a non-steady rate, with a temporary pause in ice retreat ca. 7200 cal a BP, leading to a short-lived RSL rise of ~1 m and forming a second peak to the mid-Holocene highstand. Two independent approaches were taken to constrain the long-term tectonic uplift rate of the SSIs at 0.22-0.48 m/ka, placing the tectonic contribution to the reconstructed RSL highstand between 1.4 and 2.9 m. Finally, we make comparisons to predictions from three global sea level models.

(Table S1) Age determination of Atlantic Ocean sediment cores

Well-dated benthic foraminifer oxygen isotopic records (d18O) from different water depths and locations within the Atlantic Ocean exhibit distinct patterns and significant differences in timing over the last deglaciation. This has two implications: on the one hand, it confirms that benthic d18O cannot be used as a global correlation tool with millennial-scale precision, but on the other hand, the combination of benthic isotopic records with independent dating provides a wealth of information on past circulation changes. Comparing new South Atlantic benthic isotopic data with published benthic isotopic records, we show that (1) circulation changes first affected benthic d18O in the 1000-2200 m range, with marked decreases in benthic d18O taking place at ~17.5 cal. kyr B.P. (ka) due to the southward propagation of brine waters generated in the Nordic Seas during Heinrich Stadial 1 (HS1) cold period; (2) the arrival of d18O-depleted deglacial meltwater took place later at deeper North Atlantic sites; (3) hydrographic changes recorded in North Atlantic cores below 3000 m during HS1 do not correspond to simple alternations between northern- and southern-sourced water but likely reflect instead the incursion of brine-generated deep water of northern as well as southern origin; and (4) South Atlantic waters at ~44°S and ~3800 m depth remained isolated from better-ventilated northern-sourced water masses until after the resumption of North Atlantic Deep Water (NADW) formation at the onset of the Bølling-Allerod, which led to the propagation of NADW into the South Atlantic.

Nutritional status of lactating mothers and their children 6-23 months of age in pre- and post-harvest seasons in two agro-ecological zones of rural Ethiopia

The objective of this study was to assess seasonal variation in nutritional status and feeding practices among lactating mothers and their children 6-23 months of age in two different agro-ecological zones of rural Ethiopia (lowland zone and midland zone). Food availability and access are strongly affected by seasonality in Ethiopia. However, there are few published data on the effects of seasonal food fluctuations on nutritional status and dietary diversity patterns of mothers and children in rural Ethiopia. A longitudinal study was conducted among 216 mothers in two agro-ecological zones of rural Ethiopia during pre and post-harvest seasons. Data were collected on many parameters including anthropometry, blood levels of haemoglobin and ferritin and zinc, urinary iodine levels, questionnaire data regarding demographic and household parameters and health issues, and infant and young child feeding practices, 24 h food recall to determine dietary diversity scores, and household use of iodized salt. Chi-square and multivariable regression models were used to identify independent predictors of nutritional status. A wide variety of results were generated including the following highlights. It was found that 95.4% of children were breastfed, of whom 59.7% were initially breastfed within one hour of birth, 22.2% received pre-lacteal feeds, and 50.9% of children received complementary feedings by 6 months of age. Iron deficiency was found in 44.4% of children and 19.8% of mothers. Low Zinc status was found in 72.2% of children and 67.3% of mothers. Of the study subjects, 52.5% of the children and 19.1% of the mothers were anaemic, and 29.6% of children and 10.5% of mothers had iron deficiency anaemia. Among the mothers with low serum iron status, 81.2% and 56.2% of their children had low serum zinc and iron, respectively. Similarly, among the low serum zinc status mothers, 75.2% and 45.3% of their children had low serum in zinc and iron, respectively. There was a strong correlation between the micronutrient status of the mothers and the children for ferritin, zinc and haemoglobin (P <0.001). There was also statistically significant difference between agro-ecological zones for micronutrient deficiencies among the mothers (p<0.001) but not for their children. The majority (97.6%) of mothers in the lowland zone were deficient in at least one micronutrient biomarker (zinc or ferritin or haemoglobin). Deficiencies in one, two, or all three biomarkers of micronutrient status were observed in 48.1%, 16.7% and 9.9% of mothers and 35.8%, 29.0%, and 23.5%, of children, respectively. Additionally, about 42.6% of mothers had low levels of urinary iodine and 35.2% of lactating mothers had goitre. Total goitre prevalence rates and urinary iodine levels of lactating mothers were not significantly different across agro-ecological zones. Adequately iodised salt was available in 36.6% of households. The prevalence of anaemia increased from post-harvest (21.8%) to pre-harvest seasons (40.9%) among lactating mothers. Increases were from 8.6% to 34.4% in midland and from 34.2% to 46.3% in lowland agro-ecological zones. Fifteen percent of mothers were anaemic during both seasons. Predictors of anaemia were high parity of mother and low dietary diversity. The proportion of stunted and underweight children increased from 39.8% and 27% in post-harvest season to 46.0% and 31.8% in pre-harvest season, respectively. However, wasting in children decreased from 11.6% to 8.5%. Major variations in stunting and underweight were noted in midland compared to lowland agroecological zones. Anthropometric measurements in mothers indicated high levels of undernutrition. The prevalence of undernutrition in mothers (BMI <18.5kg/m2) increased from 41.7 to 54.7% between post- and pre-harvest seasons. The seasonal effect was generally higher in the midland community for all forms of malnutrition. Parity, number of children under five years and regional variation were predictors of low BMI among lactating mothers. There were differences in minimum meal frequency, minimum acceptable diet and dietary diversity in children in pre-harvest and post-harvest seasons and these parameters were poor in both seasons. Dietary diversity among mothers was higher in lowland zone but was poor in both zones across the seasons. In conclusion, malnutrition and micronutrient deficiencies are very prevalent among lactating mothers and their children 6-23 months old in the study areas. There are significant seasonal variations in malnutrition and dietary diversity, in addition to significant differences between lowland and midland agro-ecological zones. These findings suggest a need to design effective preventive public health nutrition programs to address both the mothers’ and children’s needs particularly in the preharvest season.

The Kyoto School and Confucianism: a Confucian reading of the philosophy of history and political thought of Masaaki Kosaka

This dissertation examines the philosophy of Masaaki Kōsaka (1900-1969) from the East Asian perspective of Confucianism, which I believe is the most appropriate moral paradigm for comprehending his political speculations. Although largely neglected in post-war scholarship, Kōsaka was a prominent member of the Kyoto School during the 1930s and 40s. This was a group of Japanese thinkers strongly associated with the philosophies of Kitarō Nishida and Hajime Tanabe. Kōsaka is now best known for his participation in the three Chūō Kōron symposia held in 1941 and 1942. These meetings have been routinely denounced by liberal historians due to the participants’ support for the Pacific War and the Co-Prosperity Sphere. However, many of these liberal portrayals have failed to take into account the full extent of the group���s resistance to the military junta of Hideki Tōjō. Adopting the methods and techniques of the empirical disciplines of academic history and Orientalism, I develop an interpretative framework that is more receptive to the political values that mattered to Kōsaka as a Confucian inspired intellectual. This has necessitated the rejection of moral history, which typically prioritises modern liberal values brought a priori to the historical record of wartime Japan, as well as recognition of the different ontological foundations that inform the unique political theories of the East Asian intellectual tradition. Reinforced by the prior research of Michel Dalissier and Graham Parkes, as well as my own reading of the Confucian canon, I adopt David Williams’s thesis of ‘Confucian Revolution’ as my principle schema of interpretation. This, I believe, is better able to reconcile Kōsaka’s support for the war with his strong condemnation of the imperialist practices of the Japanese military. Moreover, acknowledging the importance of Confucianism allows us to fully appreciate Kōsaka’s strong affinity for Kant’s practical metaphysics, Hegel’s political philosophy and Ranke’s historiography.

(Table 1) Radiocarbon ages and different calibrated ages for sediment core HLY0503-18TC obtained during the HOTRAX expedition

A short sediment core from a local depression forming an intra basin on the Lomonosov Ridge, was retrieved during the Healy-Oden Trans-Arctic Expedition 2005 (HOTRAX). It contains a record of the Marine Isotope Stages (MIS) 1-3 showing exceptionally high abundances of calcareous microfossils during parts of MIS 3. Based on radiocarbon dating, linear sedimentation rates of 7-9 cm/ka persist during the last deglaciation. The Last Glacial Maximum (LGM) is partly characterized by a hiatus. Planktic foraminiferal abundance variations of Neogloboquadrina pachyderma sinistral and calcareous nannofossils reflect changes in Arctic Ocean summer sea ice coverage and probably inflow of subpolar North Atlantic water. Calibration of the radiocarbon ages, using modeled reservoir corrections from previous studies and the microfossil abundance record of the studied core, results in marine reservoir ages of 1400 years or more, at least during the last deglaciation. Paired benthic-planktic radiocarbon dated foraminiferal samples indicate a slow decrease in age difference between surface and bottom waters from the Lateglacial to the Holocene, suggesting circulation and ventilation changes.

Juniperus navicularis - a study of Portuguese population structure and fitness

Juniperus navicularis Gand. is a dioecious endemic conifer that constitutes the understory of seaside pine forests in Portugal, areas currently threatened by increasing urban expansion. The aim of this study is to assess the conservation status of previously known populations of this species located on its core area of distribution. The study was performed in south-west coast of Portugal. Three populations varying in size and pine density were analyzed. Number of individuals, population density, spatial distribution and individual characteristics of junipers were estimated. Female cone, seed characteristics and seed viability were also evaluated. Results suggest that J. navicularis populations are vulnerable because seminal recruitment is scarce, what may lead to a reduction of genetic variability due solely to vegetative propagation. This vulnerability seems to be strongly determined by climatic constraints toward increasing aridity. Ratio between male and female shrubs did not differ from 1:1 in any population. Deviations from 1:1 between mature and non-mature plants were found in all populations, denoting population ageing. Very low seed viability was observed. A major part of described Juniperus navicularis populations have disappeared through direct habitat loss to urban development, loss of fitness in drier and warmer locations and low seed viability. This study is the first to address J. navicularis conservation, and represents a valuable first step toward this species preservation. 

How to map the diversity of the audiovisual industry in the digital era. A Methodological Proposition

This article presents a methodological proposition to map the diversity of the audiovisual industry in the digital scenario by portraying the most important interactions between those who create, produce, distribute and disseminate audiovisual productions on line, paying special attention to powerful intermediaries and to small and medium independent agents. Taking as a point of departure a flexible understanding of social network analysis, the aim is to understand the structure of the audiovisual industry on the internet so that, taking into consideration a given sector, agents, their relations and the networks they give place to – as well as the structural conditions under which they operate – are studied. The aim is to answer questions such as: what is mapping, what is of interesting to map, how can it be done and what advantages and disadvantages the results will present.

Reconsidering the Origins of Forsbergh Birefringence Patterns

In 1949, P. W. Forsbergh Jr. reported spontaneous spatial ordering in the birefringence patterns seen in flux-grown BaTiO3 crystals [1], under the transmission polarized light microscope [2]. Stunningly regular square-net arrays were often only found within a finite temperature window and could be induced on both heating and cooling, suggesting genuine thermodynamic stability. At the time, Forsbergh rationalized the patterns to have resulted from the impingement of ferroelastic domains, creating a complex tessellation of variously shaped domain packets. However, evidence for the intricate microstructural arrangement proposed by Forsbergh has never been found. Moreover, no robust thermodynamic argument has been presented to explain the region of thermal stability, its occurrence just below the Curie Temperature and the apparent increase in entropy associated with the loss of the Forsbergh pattern on cooling. As a result, despite decades of research on ferroelectrics, this ordering phenomenon and its thermodynamic origin have remained a mystery. In this paper, we re-examine the microstructure of flux-grown BaTiO3 crystals, which show Forsbergh birefringence patterns. Given an absence of any obvious arrays of domain polyhedra, or even regular shapes of domain packets, we suggest an alternative origin for the Forsbergh pattern, in which sheets of orthogonally oriented ferroelastic stripe domains simply overlay one another. We show explicitly that the Forsbergh birefringence pattern occurs if the periodicity of the stripe domains is above a critical value. Moreover, by considering well-established semiempirical models, we show that the significant domain coarsening needed to generate the Forsbergh birefringence is fully expected in a finite window below the Curie Temperature. We hence present a much more straightforward rationalization of the Forsbergh pattern than that originally proposed, in which exotic thermodynamic arguments are unnecessary.