Rapid assessment of antibiotic susceptibility using a fully 3D-printed impedance- based biosensor

The sustained misuse and overuse of antibacterial agents is accelerating the emergence of antimicrobial resistance (AMR), which is becoming one of the major threats to public health. Abuse of antibiotics drives spontaneous evolution, bacterial mutation, and exchange of resistant genes through lateral gene transfer. Mitigating the worldwide impact of AMR requires enhanced antibiotic stewardship through faster diagnostic testing. In this work, we aim to tackle this issue via development of a fully 3D-printed electrochemical, gel-modified biosensor for rapid bacterial growth monitoring. By using electrochemical impedance spectroscopy, we have successfully identified growth profiles and confirmed antibiotic susceptibility of two ESKAPE pathogens, Escherichia coli and Pseudomonas aeruginosa, following overnight culture it was possible to determine antibiotic sensitivity in 90 min, altogether faster than the 24–48 h current gold standard of culture-based antimicrobial susceptibility testing with significant scope for optimisation. Results show a clear distinction between growth profiles in the presence and absence of amoxicillin, gentamicin, and fosfomycin, therefore demonstrating a rapid, cost-efficient platform for phenotypic antibiotic susceptibility testing within clinically relevant concentration ranges for conditions such as urinary tract infections and pneumonia

The Kuiper Belt and Other Debris Disks

We discuss the current knowledge of the Solar system, focusing on bodies in the outer regions, on the information they provide concerning Solar system formation, and on the possible relationships that may exist between our system and the debris disks of other stars. Beyond the domains of the Terrestrial and giant planets, the comets in the Kuiper belt and the Oort cloud preserve some of our most pristine materials. The Kuiper belt, in particular, is a collisional dust source and a scientific bridge to the dusty "debris disks" observed around many nearby main-sequence stars. Study of the Solar system provides a level of detail that we cannot discern in the distant disks while observations of the disks may help to set the Solar system in proper context.Comment: 50 pages, 25 Figures. To appear in conference proceedings book "Astrophysics in the Next Decade

Softening the Supersymmetric Flavor Problem in Orbifold GUTs

The infra-red attractive force of the bulk gauge interactions is applied to soften the supersymmetric flavor problem in the orbifold SU(5) GUT of Kawamura. Then this force aligns in the infra-red regime the soft supersymmetry breaking terms out of their anarchical disorder at a fundamental scale, in such a way that flavor-changing neutral currents as well as dangerous CP-violating phases are suppressed at low energies. It is found that this dynamical alignment is sufficiently good compared with the current experimental bounds, as long as the diagonalization matrices of the Yukawa couplings are CKM-like.Comment: 15 pages,4 figure

Model-based analyses: Promises, pitfalls, and example applications to the study of cognitive control

We discuss a recent approach to investigating cognitive control, which has the potential to deal with some of the challenges inherent in this endeavour. In a model-based approach, the researcher defines a formal, computational model that performs the task at hand and whose performance matches that of a research participant. The internal variables in such a model might then be taken as proxies for latent variables computed in the brain. We discuss the potential advantages of such an approach for the study of the neural underpinnings of cognitive control and its pitfalls, and we make explicit the assumptions underlying the interpretation of data obtained using this approach

Modification of forests by people means only 40% of remaining forests have high ecosystem integrity

Many global environmental agendas, including halting biodiversity loss, reversing land degradation, and limiting climate change, depend upon retaining forests with high ecological integrity, yet the scale and degree of forest modification remain poorly quantified and mapped. By integrating data on observed and inferred human pressures and an index of lost connectivity, we generate a globally consistent, continuous index of forest condition as determined by the degree of anthropogenic modification. Globally, only 17.4 million km2 of forest (40.5%) has high landscape-level integrity (mostly found in Canada, Russia, the Amazon, Central Africa, and New Guinea) and only 27% of this area is found in nationally designated protected areas. Of the forest inside protected areas, only 56% has high landscape-level integrity. Ambitious policies that prioritize the retention of forest integrity, especially in the most intact areas, are now urgently needed alongside current efforts aimed at halting deforestation and restoring the integrity of forests globally

Understanding the political motivations that shape Rwanda’s emergent developmental state

Twenty years after its horrific genocide, Rwanda has become a model for economic development. At the same time, its government has been criticized for its authoritarian tactics and use of violence. Missing from the often-polarized debate are the connections between these two perspectives. Synthesizing existing literature on Rwanda in light of a combined year of fieldwork, we argue that the GoR is using the developmental infrastructure to deepen state power and expand political control. We first identify the historical pressures that have motivated the Rwanda Patriotic Front (RPF) to re-imagine the political landscape. Sectarian unrest, political rivalry, wider regional insecurity, and aid withdrawal have all pressured the RPF to identify growth as strategic. However, the country’s political transformation extends beyond a prioritisation of growth and encompasses the reordering of the social and physical layout of the territory, the articulation of new ideologies and mindsets, and the provision of social services and surveillance infrastructure. Growth and social control go hand in hand. As such, the paper’s main contribution is to bring together the two sides of the Rwandan debate and place the country in a broader sociological literature about the parallel development of capitalist relations and transformations in state power

The Drosophila melanogaster Genetic Reference Panel

A major challenge of biology is understanding the relationship between molecular genetic variation and variation in quantitative traits, including fitness. This relationship determines our ability to predict phenotypes from genotypes and to understand how evolutionary forces shape variation within and between species. Previous efforts to dissect the genotype-phenotype map were based on incomplete genotypic information. Here, we describe the Drosophila melanogaster Genetic Reference Panel (DGRP), a community resource for analysis of population genomics and quantitative traits. The DGRP consists of fully sequenced inbred lines derived from a natural population. Population genomic analyses reveal reduced polymorphism in centromeric autosomal regions and the X chromosome, evidence for positive and negative selection, and rapid evolution of the X chromosome. Many variants in novel genes, most at low frequency, are associated with quantitative traits and explain a large fraction of the phenotypic variance. The DGRP facilitates genotype-phenotype mapping using the power of Drosophila genetics

Sequential targeted exome sequencing of 1001 patients affected by unexplained limb-girdle weakness

Several hundred genetic muscle diseases have been described, all of which are rare. Their clinical and genetic heterogeneity means that a genetic diagnosis is challenging. We established an international consortium, MYO-SEQ, to aid the work-ups of muscle disease patients and to better understand disease etiology. Exome sequencing was applied to 1001 undiagnosed patients recruited from more than 40 neuromuscular disease referral centers; standardized phenotypic information was collected for each patient. Exomes were examined for variants in 429 genes associated with muscle conditions. We identified suspected pathogenic variants in 52% of patients across 87 genes. We detected 401 novel variants, 116 of which were recurrent. Variants in CAPN3, DYSF, ANO5, DMD, RYR1, TTN, COL6A2, and SGCA collectively accounted for over half of the solved cases; while variants in newer disease genes, such as BVES and POGLUT1, were also found. The remaining well-characterized unsolved patients (48%) need further investigation. Using our unique infrastructure, we developed a pathway to expedite muscle disease diagnoses. Our data suggest that exome sequencing should be used for pathogenic variant detection in patients with suspected genetic muscle diseases, focusing first on the most common disease genes described here, and subsequently in rarer and newly characterized disease genes

Tides in colliding galaxies

Long tails and streams of stars are the most noticeable upshots of galaxy collisions. Their origin as gravitational, tidal, disturbances has however been recognized only less than fifty years ago and more than ten years after their first observations. This Review describes how the idea of galactic tides emerged, in particular thanks to the advances in numerical simulations, from the first ones that included tens of particles to the most sophisticated ones with tens of millions of them and state-of-the-art hydrodynamical prescriptions. Theoretical aspects pertaining to the formation of tidal tails are then presented. The third part of the review turns to observations and underlines the need for collecting deep multi-wavelength data to tackle the variety of physical processes exhibited by collisional debris. Tidal tails are not just stellar structures, but turn out to contain all the components usually found in galactic disks, in particular atomic / molecular gas and dust. They host star-forming complexes and are able to form star-clusters or even second-generation dwarf galaxies. The final part of the review discusses what tidal tails can tell us (or not) about the structure and content of present-day galaxies, including their dark components, and explains how tidal tails may be used to probe the past evolution of galaxies and their mass assembly history. On-going deep wide-field surveys disclose many new low-surface brightness structures in the nearby Universe, offering great opportunities for attempting galactic archeology with tidal tails.Comment: 46 pages, 13 figures, Review to be published in "Tidal effects in Astronomy and Astrophysics", Lecture Notes in Physics. Comments are most welcom