Addition of histamine to subcutaneously injected Plasmodium berghei sporozoites increases the parasite liver load and could facilitate whole-parasite vaccination

Background: Whole-parasite immunization remains the benchmark in malaria vaccine development. A major bottleneck in the translation of whole-parasite immunization towards routine vaccination is the mode of administration, since high degrees of protection are currently only achieved by intravenous, and not by intradermal or subcutaneous injection of viable parasites. It is known that only a small proportion of subcutaneously administered parasites reach the subsequent liver stage and low parasite liver load was shown to be associated with low protective efficacy. The objective of this analysis was to evaluate whether the liver load following subcutaneous parasite injection could be augmented by co-administration of pro-inflammatory or anti-coagulatory drugs. Methods: In the C57BL/6 Plasmodium berghei ANKA model, the clinical outcome (time to patent blood stage infection and survival) and relative parasite liver load was assessed in mice infected by subcutaneous or intramuscular sporozoite (SPZ) administration in the presence or absence of histamine and heparin supplementation in comparison to intravenously administered SPZ. In addition, a vaccination experiment was carried out to assess the protective efficacy of an improved, histamine-supplemented subcutaneous immunization regimen. Results: The parasite liver load following subcutaneous SPZ administration can be significantly increased by co-administration of histamine and heparin. A dose-dependent relation between parasite liver load and histamine dosage was observed. However, despite a relatively high parasite liver load, the protective efficacy of histamine-supplemented subcutaneous immunization remains inferior as compared to intravenous SPZ administration. Conclusions: Histamine supplementation might facilitate the future development of a non-intravenous whole-parasite vaccine. Further investigations are needed to reveal the effect of histamine supplementation and subcutaneous SPZ administration on the acquisition of protective immunity

Videnledelsens 2. bølge: en recentrering af videnledelsen gennem videnregnskabet

Knowledge Management – eller på dansk videnledelse – har været en af de hotteste management-begrebet op gennem 1990’erne. Den 1ste bølge centrerer diskussionen om det ‘kreative’ individ og har dermed en teori om, at viden er individuel og personlig. Den 2den bølge baserer sig på intellektuel kapital og videnregnskab og er rettet ind mod virksomheden som kollektiv. I de to bølger er ikke blot viden to helt forskellige ting. Ledelse af viden er også to helt forskellige ting. Ikke mindst er i-tal-sættelsen af videnressourcer for den 2den bølge en betingelse for, at videnledelse overhovedet kan praktiseres

What's in a word graph evaluation and enhancement of word lattices

During the last few years, word graphs have been gaining increasing interest within the speech community as the primary interface between speech recognizers and language processing modules. Both development and evaluation of graph-producing speech decoders require generally accepted measures of word graph quality. While the notion of recognition accuracy can easily be extended to word graphs, a meaningful measure of word graph size has not yet surfaced. We argue, that the number of derivation steps a theoretical parser would need to process all unique sub-paths in a graph could provide a measure that is both application oriented enough to be meaningful and general enough to allow a useful comparison of word recognizers across different applications. This paper discusses various measures that are used, or could be used, to measure word graph quality. Using real-life data (word graphs evaluated in the 1996 Verbmobil acoustic evaluation), it is demonstrated how different measures can affect evaluation results. Finally, some algorithms are presented that can significantly improve word graph quality with respect to specific quality measures

Shaping the spectral correlation of bi-photon quantum frequency combs by multi-frequency excitation of an SOI integrated nonlinear resonator

: We reveal the generation of a broadband (> 1.9 THz) bi-photon quantum frequency comb (QFC) in a silicon-on-insulator (SOI) Fabry-Pérot micro-cavity and the control of its spectral correlation properties. Correlated photon pairs are generated through three spontaneous four-wave mixing (SFWM) processes by using a co-polarized bi-chromatic coherent input with power P1 and P2 on adjacent resonances of the nonlinear cavity. Adjusting the spectral power ratio r = P1/(P1 + P2) allows control over the influence of each process leading to an enhancement of the overall photon pair generation rate (PGR) μ(r) by a maximal factor of μ(r = 0.5)/μ(r = 0) ≈ 1.5, compared to the overall PGR provided by a single-pump configuration with the same power budget. We demonstrate that the efficiency aND of the non-degenerate excitation SFWM process (NDP) doubles the efficiency a1 ≈ a2 of the degenerate excitation SFWM processes (DP), showing a good agreement with the provided model

Screening for type 2 diabetes in a high-risk population: Study design and feasibility of a population-based randomized controlled trial

Background: We describe the design and present the results of the first year of a population-based study of screening for type 2 diabetes in individuals at high risk of developing the disease. High risk is defined as having abdominal obesity. Methods. Between 2006 and 2007, 79,142 inhabitants of two Dutch municipalities aged 40-74 years were approached to participate in screening. Eligible participants had a self-reported waist circumference of 80 cm for women and 94 cm for men, and no known pre-existing diabetes. Of the respondents (n=20,578; response rate 26%), 16,135 were abdominally obese. In total, 10,609 individuals gave written informed consent for participation and were randomized into either the screening (n=5305) or the control arm (n=5304). Participants in the screening arm were invited to have their fasting plasma glucose (FPG) measured and were referred to their general practitioner (GP) if it was 6.1 mmol/L. In addition, blood lipids were determined in the screening arm, because abdominal obesity is often associated with cardiovascular risk factors. Participants in both arms received written healthy lifestyle information. Between-group differences were analyzed with Chi-square tests and logistic regression (categorical variables) and unpaired t-tests (continuous variables). Results: The screening attendance rate was 84.1%. Attending screening was associated with age at randomization (OR=1.03, 95% CI 1.02-1.04), being married (OR=1.57, 95% CI 1.33-1.83) and not-smoking currently (OR=0.52, 95% CI 0.44-0.62). Of the individuals screened, 5.6% had hyperglycemia, and a further 11.6% had an estimated absolute cardiovascular disease risk of 5% or higher, according to the Systematic Coronary Risk Evaluation risk model. These participants were referred to their GP. Conclusions: Self-reported home-assessed waist circumference could feasibly detect persons at high risk of hyperglycemia or cardiovascular disease. Continuation of the large-scale RCT is warranted to test the hypothesis that targeted population-based screening for type 2 diabetes leads to a significant reduction in cardiovascular morbidity and mortality