Strong gametocytocidal effect of methylene blue-based combination therapy against falciparum malaria

With the availability of new preventive and curative interventions, global malaria control has been strengthened significantly in recent years. Drugs effective in reducing malaria gametocytaemia might contribute to local elimination and possible long-term eradication. We here report on the effects of methylene blue (MB)-based malaria combination therapy on gametocytaemia during a randomised-controlled trial in Burkina Faso. An open-label randomised controlled phase II study in 180 children aged 6-10 years with uncomplicated falciparum malaria was conducted in Nouna, north-western Burkina Faso. Children were randomised to MB-artesunate (AS), MB-amodiaquine (AQ), and AS-AQ (local standard of care). Overall follow-up was for 28 days, follow-up for gametocytaemia was for 14 days. The treatment groups were similar in baseline characteristics and there was only one loss to follow-up. Compared to AS-AQ, both MB-containing regimens were associated with significantly reduced gametocyte carrier rates during follow-up days 3, 7, and 14. This effect was seen both in patients with and without P. falciparum gametocytaemia at baseline. MB reveals pronounced gametocytocidal activity which appears to act against both existing and developing P. falciparum gametocytes. MB-based combination therapy thus has the potential to reduce transmission of P. falciparum malaria in endemic regions, which has important implications for future elimination and eradication strategies

Nährstoffversorgung von Ackerbohnen im Ökologischen Landbau

Inadequate nutrient supply frequently limits biological nitrogen fixation (BNF), plant growth and grain yield of legumes. Under no-till conditions, root growth may be restrained and therefore reduce nutrient uptake. Our studies were carried out to assess the nutrient status of Vicia faba L. (particularly at the onset of bloom) in Germany by using newly created DRIS (Diagnosis and Recommendation Integrated System) norm values, Critical Nutrient Levels (CNL), and the optimum nutrient range. In a field experiment in 2010 at 4 sites (Klein-Altendorf, Wiesengut & 2 organic farms) the applied fertilizers were fermentation residues, compost, pomace, meat-bone-meal, rock-phosphate, sodium-molybdate, potassium sulphate, and borax. Nutrient elements measured in leaf samples were: C, N, S, K, Ca, P, Mg, Fe, Mn, Zn, Cu, B and Mo. As S was detected to be deficient, K2SO4 (35 kg S/ha) had a significantly positive effect on plant growth, yield and symbiosis

Non-Gaussianity Consistency Relation for Multi-field Inflation

While detection of the "local form" bispectrum of primordial perturbations would rule out all single-field inflation models, multi-field models would still be allowed. We show that multi-field models described by the $\delta N$ formalism obey an inequality between $f_{\rm NL}$ and one of the local-form {\it trispectrum} amplitudes, $\tau_{\rm NL}$, such that $\tau_{\rm NL}>\frac12(\frac65f_{\rm NL})^2$ with a possible logarithmic scale dependence, provided that 2-loop terms are small. Detection of a violation of this inequality would rule out most of multi-field models, challenging inflation as a mechanism for generating the primoridal perturbations.Comment: 5 pages. Accepted for publication in Physical Review Letter

Physics Exams that Promote Collaborative Learning

The two-stage exam is a relatively simple way to introduce collaborative learning and formative assessment into an exam. Their use is rapidly growing in the physics department at the University of British Columbia, as both students and faculty find them rewarding. In a two-stage exam students first complete and turn in the exam individually, and then, working in small groups, answer the exam questions again. During the second stage, the room is filled with spirited and effective debate with nearly every student participating. This provides students with immediate targeted feedback supplied by discussions with their peers. Furthermore, we see indications that the use of this exam format not only ensures consistency across interactive course components, but it also positively impacts how students approach the other collaborative course components. This is accomplished without losing the summative assessment of individual performance that is the expectation of exams for most instructors. In this paper we describe how to implement two- stage exams and provide arguments why they should be part of physics courses that use interactive engagement and social/collaborative learning methods

Multiple packets of neutral molecules revolving for over a mile

The level of control that one has over neutral molecules in beams dictates their possible applications. Here we experimentally demonstrate that state-selected, neutral molecules can be kept together in a few mm long packet for a distance of over one mile. This is accomplished in a circular arrangement of 40 straight electrostatic hexapoles through which the molecules propagate over 1000 times. Up to 19 packets of molecules have simultaneously been stored in this ring structure. This brings the realization of a molecular low-energy collider within reach

Neue Methoden zur Bekämpfung des Echten Mehltaus im Ökologischen Landbau

Blattoberflächen-modifizierende Salzapplikationen sollten als Bekämpfungsmittel gegen Echten Mehltau an Tomaten und Gurken getestet werden hinsichtlich folgender Eigenschaften: - Wirkung verschiedener Salze - Blattverträglichkeit - Untersuchung der unterschiedlichen Wirkungsmechanismen mittels REM - Übertragbarkeit in praxisnahe Versuche. Die verschiedenen Salzlösungen und Kombinationen aus diesen Salzen unterschieden sich deutlich in ihrer Wirkung auf Gurkenmehltau. Die beste Wirkung ergab sich mit allenfalls geringer Schädigung des Blattes mit 0,1% MnCl2, 1 % Patentkali (K2SO4/MgSO4) und 1% Knöterichextrakt. MnCl2 liegt auf Grund seines niedrigen Deliqueszenzpunktes ständig gelöst auf der Blattoberfläche vor, wogegen sich Knöterichextrakt und Patentkali auf der Blattoberfläche in einer Art „Salzkriechen“ verteilen durch häufigen Wechsel zwischen Trocknen und Wiederverflüssigung. Salzschäden ließen sich verringern durch Zusatz von Netzmitteln zur Sprühlösung. Rasterelektronische Visualisierung zeigte für alle untersuchten Lösungen einen direkt toxischen Effekt auf die Mehltausporen und ihre Hyphen in jeder Entwicklungsphase des Pilzes. Eine Verbesserung des Nährstoffstatus der Pflanzen scheidet als Wirkungsmechanismus aus, da alle Pflanzen optimal ernährt waren und die Behandlungen zu keinen signifikanten Veränderungen der Nährstoffgehalte in den Blättern führten. Besonders chloridische Salze führten z.T. zu erheblicher Nekrotisierung der Blätter. Da diese Salzlösungen jedoch auch in geringer Konzentration in der Lage waren, die Ausbreitung des Echten Mehltau effektiv zu verhindern, sollten Möglichkeiten zur Mikrodosierung dieser Salze geprüft werden. Extreme Witterungsbedingungen im Sommer 2003 führten dazu, dass Praxistests nicht ausgeführt oder normal beendet werden konnten. Es gilt jedoch als sicher, dass einige der untersuchten Salzmischungen in geringen Konzentrationen (zw. 0,1 und 1%) den Befall mit Echten Mehltaupilzen effektiv reduzieren können, ohne Blattoberflächen zu schädigen

Safety and efficacy of methylene blue combined with artesunate or amodiaquine for uncomplicated falciparum malaria

Besides existing artemisinin-based combination therapies, alternative safe, effective and affordable drug combinations against falciparum malaria are needed. Methylene blue (MB) was the first synthetic antimalarial drug ever used, and recent studies have been promising with regard to its revival in malaria therapy. The objective of this study was to assess the safety and efficacy of two MB-based malaria combination therapies, MB-artesunate (AS) and MB-amodiaquine (AQ), compared to the local standard of care, AS-AQ, in Burkina Faso. Open-label randomised controlled phase II study in 180 children aged 6-10 years with uncomplicated falciparum malaria in Nouna, north-western Burkina Faso. Follow-up was for 28 days and analysis by intention-to-treat. The treatment groups were similar in baseline characteristics and there was only one loss to follow-up. No drug-related serious adverse events and no deaths occurred. MB-containing regimens were associated with mild vomiting and dysuria. No early treatment failures were observed. Parasite clearance time differed significantly among groups and was the shortest with MB-AS. By day 14, the rates of adequate clinical and parasitological response after PCR-based correction for recrudescence were 87% for MB-AS, 100% for MB-AQ (p = 0.004), and 100% for AS-AQ (p = 0.003). By day 28, the respective figure was lowest for MB-AS (62%), intermediate for the standard treatment AS-AQ (82%; p = 0.015), and highest for MB-AQ (95%; p<0.001; p = 0.03). MB-AQ is a promising alternative drug combination against malaria in Africa. Moreover, MB has the potential to further accelerate the rapid parasite clearance of artemisinin-based combination therapies. More than a century after the antimalarial properties of MB had been described, its role in malaria control deserves closer attention. ClinicalTrials.gov NCT00354380

The k-Point Random Matrix Kernels Obtained from One-Point Supermatrix Models

The k-point correlation functions of the Gaussian Random Matrix Ensembles are certain determinants of functions which depend on only two arguments. They are referred to as kernels, since they are the building blocks of all correlations. We show that the kernels are obtained, for arbitrary level number, directly from supermatrix models for one-point functions. More precisely, the generating functions of the one-point functions are equivalent to the kernels. This is surprising, because it implies that already the one-point generating function holds essential information about the k-point correlations. This also establishes a link to the averaged ratios of spectral determinants, i.e. of characteristic polynomials

The promoter of human p22/PACAP response gene 1 (PRG1) contains functional binding sites for the p53 tumor suppressor and for NFκB

AbstractWe describe functional binding sites for the tumor suppressor p53 and for NFκB residing in the promoter of the novel human early response gene p22/PRG1 (IEX-1/DIF-2). Gel shift and supershift assays demonstrate binding of p53 and NFκB to their corresponding sites in vitro. CAT-reporter gene assays show transactivation of the human p22/PRG1 promoter by p53 in Hep3B cells stably transfected with a temperature-sensitive mutant p53, but not in p53-deficient Hep3B cells. TNFα induced NFκB dependent transactivation was shown in HepG2 cells or in 818-4 pancreatic cancer cells. These data imply that human p22/PRG1 is a target gene for p53 and NFκB involved in growth regulation and stress response