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Abstract Plasma metabolomics holds potential for precision medicine, but limited information is available to compare the performance of such methods across multiple cohorts. We compared plasma metabolite profiles after an overnight fast in 11,309 participants of five population-based Swedish cohorts (50–80 years, 52% women). Metabolite profiles were uniformly generated at a core laboratory (Metabolon Inc.) with untargeted liquid chromatography mass spectrometry and a comprehensive reference library. Analysis of a second sample obtained one year later was conducted in a subset. Of 1629 detected metabolites, 1074 (66%) were detected in all cohorts while only 10% were unique to one cohort, most of which were xenobiotics or uncharacterized. The major classes were lipids (28%), xenobiotics (22%), amino acids (14%), and uncharacterized (19%). The most abundant plasma metabolome components were the major dietary fatty acids and amino acids, glucose, lactate and creatinine. Most metabolites displayed a log-normal distribution. Temporal variability was generally similar to clinical chemistry analytes but more pronounced for xenobiotics. Extensive metabolite-metabolite correlations were observed but mainly restricted to within each class. Metabolites were broadly associated with clinical factors, particularly body mass index, sex and renal function. Collectively, our findings inform the conduct and interpretation of metabolite association and precision medicine studies.

The introduction of the biological control agent Torymus sinensis Kamijo (Hymenoptera, Chalcidoidea, Torymidae) to control the populations of the chestnut gall wasp Dryocosmus kuriphilus Yasumatsu (Hymenoptera, Cynipidae) is considered one of the successful programs in biological control. The species was involved in interspecific hybridisation in Japan and the specimens imported into Europe were derived from this hybrid lineage, showing signs of introgression. The discovery of mitochondrial haplotypes or possible Enolase haplotypes from T. beneficus or of specimens with shorter ovipositor does not necessarily imply that T. beneficus is present in Europe, only that the European specimens are of hybrid origin. Of the native European Torymus species associated with D. kuriphilus, the molecular and morphometric results indicate Torymus notatus (Walker) as the closest species to T. sinensis. The two are part of the same species-group (cyaneus group), are nested together in the multivariate ratio analysis and are the closest genetically based on all three nuclear markers: Enolase (1.5% divergence), Wingless (2%) and ITS2 (13%). However, on the mitochondrial marker COI the closest species is Torymus rubi (Schrank) at 9.9% divergence. As such, T. notatus is the most likely candidate for accidental interspecific hybridisation if this is to happen in Europe. We provide an illustrated identification key for the European species of Torymus associated with D. kuriphilus, an important but lacking tool for biological control programs.

Despite increasing attention to the potential benefits of infusing computational thinking into content area classrooms, more research is needed to examine how teachers integrate disciplinary content and CT as part of their pedagogical practices. This study traces how middle and high school teachers (n = 24) drew on their existing knowledge and their experiences in a STEM professional development program to infuse CT into their teaching. Our work is grounded in theories of TPACK and TPACK-CT, which leverage teachers’ knowledge of technology for computational thinking (CT), CT as a disciplinary pedagogical practice, and STEM content knowledge. Findings identify three key pedagogical supports that teachers utilized and transformed as they taught CT-infused lessons (articulating a key purpose for CT infusion, scaffolding, and collaborative contexts), as well as barriers that caused teachers to adapt or abandon their lessons. Implications include suggestions for future research on CT infusion into secondary classrooms, as well as broader recommendations to support teachers in applying STEM professional development content to classroom practice.

BACKGROUND:The emergence of pre-extensively and extensively drug-resistant tuberculosis (Pre-XDR/XDR-TB) is the major hurdle for TB prevention and care programs especially in developing countries like Ethiopia. The less emphasis on universal access to laboratory techniques for the rapid diagnosis of TB and drug susceptibility testing (DST) makes the management of MDR-TB a challenge. Early detection of second line anti-TB drugs resistance is essential to reduce transmission of Pre-XDR/XDR-TB strains and adjusting the treatment regimen in MDR-TB. OBJECTIVE:To determine the prevalence and resistance pattern of Pre-XDR- and XDR-TB among MDR-TB patients in the Amhara region, Ethiopia. METHODS:A cross sectional study was carried out in nine MDR-TB treatment centers in the Amhara region. Sputum samples were collected from all pulmonary rifampicin resistant (RR) or MDR-TB patients prior to anti-TB treatment. Lӧwenstein-Jensen (LJ) culture, Ziehl Neelsen (ZN) smear, MTBDRplus and MTBDRsl assays were performed according to the standard procedures. Data were analyzed using SPSS 20 software. Chi-square and/or Fishers exact test was employed. RESULTS:Overall, 6.3% of MDR-TB isolates were resistant to at least one second line drugs. Pre-XDR-TB and XDR-TB isolates accounted 5.7% and 0.6% respectively. Moreover, 3.4% were resistant to FQs and 3.4% were resistant to second line injectable drugs. All isolates were susceptible for low level kanamycin. Almost all pre-XDR-TB strains (90%) were previously treated with anti-TB drugs. Drug resistant Mycobacterium tuberculosis isolates were disproportionately distributed in districts of the Amhara region and the majorities were concentrated in urban areas. CONCLUSIONS:The high proportion of MDR-TB patients resistant to at least one second line drug is alarming. Strengthening the laboratory facilities to monitor pre-XDR and XDR-TB patients is crucial. The TB programs need to give emphasis on the effective and rational use of second line drugs for newly diagnosed MDR-TB patients to prevent the emergence of pre-XDR/XDR-TB strains.

Abstract The PREDICTS project—Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (https://www.nhm.ac.uk/our-science/our-work/biodiversity/predicts.html)—has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.

Background and Context: Using a transformative learning framework, this qualitative study examines the perspectives and practices of 70 middle and high school content area teachers who attended two or more summer professional development workshops. Objective: This study describes how teachers' disciplinary perspectives and backgrounds influence their understanding of CT infusion and their implementation of CT-infused lessons. Method: Data sources for this qualitative comparative case study analysis included: retrospective video reflections, implementation surveys, post-PD surveys, and instructional materials. Findings: Analysis revealed differences in terms of disorienting dilemmas teachers faced, shifts in their frames of reference, the form of classroom CT infusion, and their integration of specific CT concepts. Implications: This study contributes a comparative analysis of how teachers from different content areas come to understand CT infusion and implement CT-infused pedagogical practices to support their disciplinary teaching. Findings indicate the importance of including all teachers, STEM and non-STEM, in CT infusion efforts.

In response to the financial crisis of 2008, the Federal Reserve radically increased the monetary base. Banks responded by increasing excess reserves rather than increasing bank loans, and the public responded with a substantial flight to liquidity in the form of currency and demand deposits. As a result, the money-supply multipliers substantially decreased, so that the actual money supply measures grew more moderately than the base. The sustained multiplier-collapse spawned reexamination of monetary versus fiscal theories of price-level determination. This paper, however, presents decompositions of the money-multiplier collapse into changes in the currency-to-deposit ratios, and changes in the reserve-to-deposit ratio. By doing so, possible near-term increases in the multipliers are simulated so that the possibility of either full or partial restoration to their pre-crisis levels is assessed. Policy possibilities for controlling the money supply over various horizons follow. This analysis illustrates the Federal Reserve’s exit dilemma that results from its financial-crisis policy.

How does the body's immune system strike the delicate balance between under- and over-response? A new study shows that glucocorticoids limit the production of the proinflammatory cytokine interleukin-12 by dendritic cells in response to invading bacteria, thereby helping to avoid sepsis. Read the Research Article.

Work on rats and humans reveals a role for reduction in the levels of the stress-regulated protein kinase SGK1 in the development of post-traumatic stress disorder. Read the Research Article.

A new study shows that synaptotagmins, known to regulate the fusion of neurotransmitter vesicles with synaptic membranes, are also needed for the prior tethering and priming of vesicles. Read the Research Article.

HIV-1 is already known to have an extremely fast mutation rate, but a new study shows it to be more than two orders of magnitude higher than previously believed, and that this is largely due to host cytidine deaminases. Read the Research Article.

A new study shows that during repair of DNA, the effect of a single-strand annealing protein is to destabilize DNA duplex formation so that annealing only occurs between perfectly matched strands; the protein then clamps the strands together for repair. Read the Research Article.

To what extent does the spinal cord play a role in the learning of motor tasks? A new study that simultaneously images the brain and spinal cord shows that the spinal cord is actively and independently involved in the earliest stages of motor learning.

A new study identifies an unexpected role for lysophosphatidic acid in modulating the strength of both excitatory and inhibitory synapses in the brain, but by different mechanisms. Read the accompanying Research Article.

The protein P0 has long been known to play a crucial role in holding together the myelin sheath that insulates peripheral nerves. A new study reveals that P0 is also important for organizing the nodes of Ranvier that occupy the gaps in the insulation. Read the Research Article.

A new study adds further complexity to the mammalian circadian clock by revealing that the CRY protein has an additional unsuspected feedback role in facilitating a crucial regulatory phosphorylation event. Read the Research Article.