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Background Methylene blue (MB) was the first synthetic antimalarial to be discovered and was used during the late 19th and early 20th centuries against all types of malaria. MB has been shown to be effective in inhibiting Plasmodium falciparum in culture, in the mouse model and in rhesus monkeys. MB was also shown to have a potent ex vivo activity against drug-resistant isolates of P. falciparum and P. vivax . In preclinical studies, MB acted synergistically with artemisinin derivates and demonstrated a strong effect on gametocyte reduction in P. falciparum . MB has, thus, been considered a potentially useful partner drug for artemisinin-based combination therapy (ACT), particularly when elimination is the final goal. The aim of this study was to review the scientific literature published until early 2017 to summarise existing knowledge on the efficacy and safety of MB in the treatment of malaria. Methods This systematic review followed PRISMA guidelines. Studies reporting on the efficacy and safety of MB were systematically searched for in relevant electronic databases according to a pre-designed search strategy. The search (without language restrictions) was limited to studies of humans published until February 2017. Results Out of 474 studies retrieved, a total of 22 articles reporting on 21 studies were eligible for analysis. The 21 included studies that reported data on 1504 malaria patients (2/3 were children). Older studies were case series and reports on MB monotherapy while recent studies were mainly controlled trials of combination regimens. MB was consistently shown to be highly effective in all endemic areas and demonstrated a strong effect on P. falciparum gametocyte reduction and synergy with ACT. MB treatment was associated with mild urogenital and gastrointestinal symptoms as well as blue coloration of urine. In G6PD-deficient African individuals, MB caused a slight but clinically non-significant haemoglobin reduction. Conclusions More studies are needed to define the effects of MB in P. falciparum malaria in areas outside Africa and against P. vivax malaria. Adding MB to ACT could be a valuable approach for the prevention of resistance development and for transmission reduction in control and elimination programs. Systematic review registration This study is registered at PROSPERO (registration number CRD42017062349 ).

Switching to a diet lower in red meat has the potential to reduce greenhouse gas emissions. Using a unique time series of daily sales data from three German university canteens from 2017 to 2019, we analyse the effects of a monthly Veggie Day in a food-away-from-home context. We find that the temporary ban on meat dishes did not lead to a widespread boycott – as the heated public debates might have suggested. In our setting, a Veggie Day could reduce greenhouse gas emissions by up to 66%. However, especially at the site with a higher share of meat eaters on regular days, up to 22% of customers bypassed the meat-free main dishes on Veggie Days and ate at other on-site alternatives where meat was available. However, total on-site sales did not decrease significantly. Students were less likely to switch to alternatives than staff and guests. A less stringent implementation of a Veggie Day where only beef dishes were removed from the menu, did not result in a significant shift to alternatives but could reduce emissions by up to 51%.

Metrics are a useful way to assess biocatalyst performance and, when compared to techno-economic targets, can help set goals for further enzyme and bioprocess research and development. Here, we outline some of the remaining challenges to ensure wider acceptance of this approach, both in industry and in academia.

This paper reports on a randomized control trial involving children less than 3 years old and their mothers who were regarded at risk of maltreating their children by referral agencies. Mothers’ risk status derived from a heavy trauma burden (average exposure over the first 18 years of their lives to 10 possible adverse childhood experiences [ACEs] was >5), mental health challenges (15%–28% had experienced a prior psychiatric hospitalization), and prior removal of a child to foster care (20%). Mothers were randomly assigned to either a widely used parenting class known as Systematic Training for Effective Parenting (STEP) or the Group Attachment-Based Intervention (GABI), a multifamily 26-week treatment. The resulting mother–child pairs available for consideration in this baseline versus end-of-treatment report were 35 families in the STEP arm and 43 families in the GABI arm. The focus of this paper is the outcome measure of observed parent–child relationship assessed with the Coding of Interactive Behavior (Feldman, 1998) collected at baseline and end of treatment. In comparison to STEP, results indicated that GABI was linked to significant improvements in maternal supportive presence and dyadic reciprocity, and significant declines in maternal hostility and dyadic constriction (proxies for risk of child maltreatment). These medium-to large-sized effects remained significant even after controlling for mothers’ prior ACEs in analysis of covariance procedures. In addition, two small interaction effects of ACEs by treatment type were found, underlining the need for, and value of, treatments that are sensitive to parents’ traumatic histories.

Weichselian cryogenic calcites collected in what is referred to as the Rätselhalle of the Herbstlabyrinth-Advent Cave system are structurally classified as rhombohedral crystals and spherulitic aggregates. The carbon and oxygen isotopic composition of these precipitates (δ13C = +0.6 to −7.3‰ δ18O = −6.9 to −18.0‰) corresponds to those of known slowly precipitated cryogenic cave calcites under conditions of isotopic equilibrium between water and ice of Central European caves. The carbon and oxygen isotopic composition varies between different caves which is attributed to the effects of cave air ventilation before the freezing started. By petrographic and geochemical comparisons of Weichselian cryogenic calcite with recent to sub-recent precipitates as well as Weichselian non-cryogenic calcites of the same locality, a model for the precipitation of these calcites is proposed. While the recent and sub-recent pool-calcites isotopically match the composition of interglacial speleothems (stalagmites, etc.), isotope ratios of Weichselian non-cryogenic pool-calcites reflect cooler conditions. Weichselian cryogenic calcites show a trend towards low δ18O values with higher carbon isotope ratios reflecting slow freezing of the precipitating solution. In essence, the isotope geochemistry of the Weichselian calcites reflects the climate history changing from overall initial permafrost conditions to permafrost-free and subsequently to renewed permafrost conditions. Judging from the data compiled here, the last permafrost stage in the Rätselhalle is followed by a warm period (interstadial and/or Holocene). During this warmer period, the cave ice melted and cryogenic and non-cryogenic Weichselian calcite precipitates were deposited on the cave ground or on fallen blocks, respectively.

A simple and energy-efficient photonic system to generate continuously tunable, low phase noise, sub-THz waves based on COTS components is presented. The optical scheme is based on the use of a commercial vertical cavity surface emitting laser under gain switching modulation that provides a very flat optical frequency comb generator (OFCG) with 23 modes in a 20 dB bandwidth. The laser only needs 15 dBm continuous wave radiofrequency input power and 9 mA of bias current to provide this OFCG. Two optical injection locking stages filter and amplify the two desired modes that are detected in a photodiode to produce the desired sub-THz signal at the frequency difference of these two selected modes. As an example, demonstrated is the generation of a very stable 88.2 GHz tone with lower linewidth than 10 Hz using a reference of 4.2 GHz to generate the OFCG.

Elder et al outline current knowledge of the three autosomal dominant types of porphyrias: acute intermittent porphyria, variegate porphyria, and hereditary coproporphyria.

A hands on guide to web scraping and text mining for both beginners and experienced users of R * Introduces fundamental concepts of the main architecture of the web and databases and covers HTTP, HTML, XML, JSON, SQL. * Provides basic techniques to query web documents and data sets (XPath and regular expressions). * An extensive set of exercises are presented to guide the reader through each technique. * Explores both supervised and unsupervised techniques as well as advanced techniques such as data scraping and text management. * Case studies are featured throughout along with examples for each technique presented. * R code and solutions to exercises featured in the book are provided on a supporting website.