Subglacial swamps

peer-reviewedThe existence of both water and sediment at the bed of ice streams is well documented, but there is a lack of fundamental understanding about the mechanisms of ice, water and sediment interaction. We pose a model to describe subglacial water flow below ice sheets, in the presence of a deformable sediment layer. Water flows in a rough-bedded film; the ice is supported by larger clasts, but there is a millimetric water layer submerging the smaller particles. Partial differential equations describing the water film are derived from a description of the dynamics of ice, water and mobile sediment. We assume that sediment transport is possible, either as fluvial bedload, but more significantly by ice-driven shearing and by internal squeezing. This provides an instability mechanism for rivulet formation; in the model, downstream sediment transport is compensated by lateral squeezing of till towards the incipient streams. We show that the model predicts the formation of shallow, swamp-like streams, with a typical depth of the order of centimetres. The swamps are stable features, typically with a width of the order of tens to hundreds of metres.PUBLISHEDpeer-reviewe

Online unit clustering in higher dimensions

We revisit the online Unit Clustering and Unit Covering problems in higher dimensions: Given a set of $n$ points in a metric space, that arrive one by one, Unit Clustering asks to partition the points into the minimum number of clusters (subsets) of diameter at most one; while Unit Covering asks to cover all points by the minimum number of balls of unit radius. In this paper, we work in $\mathbb{R}^d$ using the $L_\infty$ norm. We show that the competitive ratio of any online algorithm (deterministic or randomized) for Unit Clustering must depend on the dimension $d$. We also give a randomized online algorithm with competitive ratio $O(d^2)$ for Unit Clustering}of integer points (i.e., points in $\mathbb{Z}^d$, $d\in \mathbb{N}$, under $L_{\infty}$ norm). We show that the competitive ratio of any deterministic online algorithm for Unit Covering is at least $2^d$. This ratio is the best possible, as it can be attained by a simple deterministic algorithm that assigns points to a predefined set of unit cubes. We complement these results with some additional lower bounds for related problems in higher dimensions.Comment: 15 pages, 4 figures. A preliminary version appeared in the Proceedings of the 15th Workshop on Approximation and Online Algorithms (WAOA 2017

Genome-wide sexually antagonistic variants reveal long-standing constraints on sexual dimorphism in fruit flies

The evolution of sexual dimorphism is constrained by a shared genome, leading to ‘sexual antagonism’, in which different alleles at given loci are favoured by selection in males and females. Despite its wide taxonomic incidence, we know little about the identity, genomic location, and evolutionary dynamics of antagonistic genetic variants. To address these deficits, we use sex-specific fitness data from 202 fully sequenced hemiclonal Drosophila melanogaster fly lines to perform a genome-wide association study (GWAS) of sexual antagonism. We identify approximately 230 chromosomal clusters of candidate antagonistic single nucleotide polymorphisms (SNPs). In contradiction to classic theory, we find no clear evidence that the X chromosome is a hot spot for sexually antagonistic variation. Characterising antagonistic SNPs functionally, we find a large excess of missense variants but little enrichment in terms of gene function. We also assess the evolutionary persistence of antagonistic variants by examining extant polymorphism in wild D. melanogaster populations and closely related species. Remarkably, antagonistic variants are associated with multiple signatures of balancing selection across the D. melanogaster distribution range and in their sister species D. simulans, indicating widespread and evolutionarily persistent (about 1 million years) genomic constraints on the evolution of sexual dimorphism. Based on our results, we propose that antagonistic variation accumulates because of constraints on the resolution of sexual conflict over protein coding sequences, thus contributing to the long-term maintenance of heritable fitness variation

Pseudo-arthrosis repair of a posterior cruciate ligament avulsion fracture

A pseudo-arthrosis repair of a 4-year-old bony avulsion fracture of the PCL using a minimally invasive technique, screw fixation, and bone grafting is reported. The case presented seems to be rather unique due to the fragment size and the approach for pseudo-arthrosis repair. There was a good functional result following minimally invasive pseudo-arthrosis repair of a posterior cruciate ligament avulsion fracture. There are no previous reports of similar pseudo-arthrosis repairs, and other authors report good results of delayed refixation of PCL avulsion fractures. Therefore, refixation and pseudo-arthrosis repair should be considered as a viable treatment

A crowd of BashTheBug volunteers reproducibly and accurately measure the minimum inhibitory concentrations of 13 antitubercular drugs from photographs of 96-well broth microdilution plates

Tuberculosis is a respiratory disease that is treatable with antibiotics. An increasing prevalence of resistance means that to ensure a good treatment outcome it is desirable to test the susceptibility of each infection to different antibiotics. Conventionally, this is done by culturing a clinical sample and then exposing aliquots to a panel of antibiotics, each being present at a pre-determined concentration, thereby determining if the sample isresistant or susceptible to each sample. The minimum inhibitory concentration (MIC) of a drug is the lowestconcentration that inhibits growth and is a more useful quantity but requires each sample to be tested at a range ofconcentrations for each drug. Using 96-well broth micro dilution plates with each well containing a lyophilised pre-determined amount of an antibiotic is a convenient and cost-effective way to measure the MICs of several drugs at once for a clinical sample. Although accurate, this is still an expensive and slow process that requires highly-skilled and experienced laboratory scientists. Here we show that, through the BashTheBug project hosted on the Zooniverse citizen science platform, a crowd of volunteers can reproducibly and accurately determine the MICs for 13 drugs and that simply taking the median or mode of 11-17 independent classifications is sufficient. There is therefore a potential role for crowds to support (but not supplant) the role of experts in antibiotic susceptibility testing

Enriching Peptide Libraries for Binding Affinity and Specificity Through Computationally Directed Library Design

Peptide reagents with high affinity or specificity for their target protein interaction partner are of utility for many important applications. Optimization of peptide binding by screening large libraries is a proven and powerful approach. Libraries designed to be enriched in peptide sequences that are predicted to have desired affinity or specificity characteristics are more likely to yield success than random mutagenesis. We present a library optimization method in which the choice of amino acids to encode at each peptide position can be guided by available experimental data or structure-based predictions. We discuss how to use analysis of predicted library performance to inform rounds of library design. Finally, we include protocols for more complex library design procedures that consider the chemical diversity of the amino acids at each peptide position and optimize a library score based on a user-specified input model.National Institute of General Medical Sciences (U.S.) (Award R01 GM110048

No Detectable Fertility Benefit from a Single Additional Mating in Wild Stalk-Eyed Flies

Background: Multiple mating by female insects is widespread, and the explanation(s) for repeated mating by females has been the subject of much discussion. Females may profit from mating multiply through direct material benefits that increase their own reproductive output, or indirect genetic benefits that increase offspring fitness. One particular direct benefit that has attracted significant attention is that of fertility assurance, as females often need to mate multiply to achieve high fertility. This hypothesis has never been tested in a wild insect population.Methodology/Principal Findings: Female Malaysian stalk-eyed flies (Teleopsis dalmanni) mate repeatedly during their lifetime, and have been shown to be sperm limited under both laboratory and field conditions. Here we ask whether receiving an additional mating alleviates sperm limitation in wild females. In our experiment one group of females received a single additional mating, while a control group received an interrupted, and therefore unsuccessful, mating. Females that received an additional mating did not lay more fertilised eggs in total, nor did they lay proportionately more fertilised eggs. Female fertility declined significantly through time, demonstrating that females were sperm limited. However, receipt of an additional mating did not significantly alter the rate of this decline.Conclusions/Significance: Our data suggest that the fertility consequences of a single additional mating were small. We discuss this effect (or lack thereof), and suggest that it is likely to be attributed to small ejaculate size, a high proportion of failed copulations, and the presence of X-linked meiotic drive in this species

Bilateral sternoclavicular joint septic arthritis secondary to indwelling central venous catheter: a case report

<p>Abstract</p> <p>Introduction</p> <p>Septic arthritis of the sternoclavicular joint is rare, comprising approximately 0.5% to 1% of all joint infections. Predisposing causes include immunocompromising diseases such as diabetes, HIV infection, renal failure and intravenous drug abuse.</p> <p>Case presentation</p> <p>We report a rare case of bilateral sternoclavicular joint septic arthritis in an elderly patient secondary to an indwelling right subclavian vein catheter. The insidious nature of the presentation is highlighted. We also review the literature regarding the epidemiology, investigation and methods of treatment of the condition.</p> <p>Conclusion</p> <p>SCJ infections are rare, and require a high degree of clinical suspicion. Vague symptoms of neck and shoulder pain may cloud the initial diagnosis, as was the case in our patient. Surgical intervention is often required; however, our patient avoided major intervention and settled with parenteral antibiotics and washout of the joint.</p

The use of mechanistic reasoning in assessing coronavirus interventions

Funder: Marie Curie; Id: http://dx.doi.org/10.13039/501100000654Funder: Wellcome; Id: http://dx.doi.org/10.13039/100010269Funder: MRC: Medical Research CouncilFunder: NIHR: National Institute For Health ResearchAbstract: Rationale: Evidence‐based medicine (EBM), the dominant approach to assessing the effectiveness of clinical and public health interventions, focuses on the results of association studies. EBM+ is a development of EBM that systematically considers mechanistic studies alongside association studies. Aims and objectives: To explore examples of the importance of mechanistic evidence to coronavirus research. Methods: We have reviewed the mechanistic evidence in four major areas that are relevant to the management of COVID‐19. Results and conclusions: (a) Assessment of combination therapy for MERS highlights the need for systematic assessment of mechanistic evidence. (b) That hypertension is a risk factor for severe disease in the case of SARS‐CoV‐2 suggests that altering hypertension treatment might alleviate disease, but the mechanisms are complex, and it is essential to consider and evaluate multiple mechanistic hypotheses. (c) Confidence that public health interventions will be effective requires a detailed assessment of social and psychological components of the mechanisms of their action, in addition to mechanisms of disease. (d) In particular, if vaccination programmes are to be effective, they must be carefully tailored to the social context; again, mechanistic evidence is crucial. We conclude that coronavirus research is best situated within the EBM+ evaluation framework