Transcriptional downregulation of agr expression in Staphylococcus aureus during growth in human serum can be overcome by constitutively active mutant forms of the sensor kinase AgrC

The temporal and cell density-dependent regulation of expression of virtually all the Staphylococcus aureus virulon is under the control of the agr (accessory gene regulatory) operon. The expression of the agr operon is subject to transcriptional regulation by the AgrA/C two-component response regulator/sensor kinase pair. During bacteraemia, a frequent syndrome caused by methicillin-resistant S. aureus (MRSA), the transcriptional downregulation of agr expression has been attributed to the sequestration of the quorum-signalling molecule auto-inducing peptide (AIP) by the human serum component apolipoprotein B as part of an innate immune response to infection. However, it is not known whether transcriptional downregulation of agr expression during growth in human serum is additionally subjected to regulation by transcription regulatory proteins that either directly or indirectly affect transcription from the agr operon promoters. Here, using chromosomal fluorescence reporters of agr expression in S. aureus, we show that the transcriptional downregulation of agr expression in human serum can be overcome using constitutive active mutant forms of AgrC. Therefore, it seems that the sequestration of the AIP is likely to be the only mechanism by which the host innate immune response limits agr expression at the transcriptional level to maintain the host–pathogen balance towards a noninvasive outcome

Phase II study of tight glycaemic control in COPD patients with exacerbations admitted to the acute medical unit.

BACKGROUND: Hyperglycaemia is associated with poor outcomes from exacerbations of chronic obstructive pulmonary disease (COPD). Glycaemic control could improve outcomes by reducing infection, inflammation and myopathy. Most patients with COPD are managed on the acute medical unit (AMU) outside intensive care (ICU). OBJECTIVE: To determine the feasibility, safety and efficacy of tight glycaemic control in patients on an AMU. DESIGN: Prospective, non-randomised, phase II, single-arm study of tight glycaemic control in COPD patients with acute exacerbations and hyperglycaemia admitted to the AMU. Participants received intravenous, then subcutaneous, insulin to control blood glucose to 4.4-6.5 mmol/l. Tight glycaemic control was evaluated: feasibility, protocol adherence; acceptability, patient questionnaire; safety, frequency of hypoglycaemia (capillary blood glucose (CBG) <2.2 mmol/l and 2.2-3.3 mmol/l); efficacy, median CBG, fasting CBG, proportion of measurements/time in target range, glycaemic variability. RESULTS: were compared with 25 published ICU studies. Results 20 patients (10 females, age 71 ± 9 years; forced expiratory volume in 1 s: 41 ± 16% predicted) were recruited. Tight glycaemic control was feasible (78% CBG measurements and 89% of insulin-dose adjustments were adherent to protocol) and acceptable to patients. 0.2% CBG measurements were <2.2 mmol/l and 4.1% measurements 2.2-3.3 mmol/l. The study CBG and proportion of measurements/time in target range were similar to that of ICU studies, whereas the fasting CBG was lower, and the glycaemic variability was greater. CONCLUSIONS: Tight glycaemic control is feasible and has similar safety and efficacy on AMU to ICU. However, as more recent ICU studies have shown no benefit and possible harm from tight glycaemic control, alternative strategies for blood glucose control in COPD exacerbations should now be explored. Trial registration number ISRCTN: 42412334. http://Clinical.Trials.gov NCT00764556

DeepKey: Towards End-to-End Physical Key Replication From a Single Photograph

This paper describes DeepKey, an end-to-end deep neural architecture capable of taking a digital RGB image of an 'everyday' scene containing a pin tumbler key (e.g. lying on a table or carpet) and fully automatically inferring a printable 3D key model. We report on the key detection performance and describe how candidates can be transformed into physical prints. We show an example opening a real-world lock. Our system is described in detail, providing a breakdown of all components including key detection, pose normalisation, bitting segmentation and 3D model inference. We provide an in-depth evaluation and conclude by reflecting on limitations, applications, potential security risks and societal impact. We contribute the DeepKey Datasets of 5, 300+ images covering a few test keys with bounding boxes, pose and unaligned mask data.Comment: 14 pages, 12 figure

Level of adherence to prescribed exercise in spondyloarthritis and factors affecting this adherence: a systematic review

Adherence is a primary determinant of the effectiveness of any intervention. Exercise is considered essential in the management of spondyloarthritis (SpA); however, the overall adherence to exercise programmes and factors affecting adherence are unknown. The aim of this systematic review was to examine measures of, and factors influencing adherence to, prescribed exercise programmes in people with SpA. A search was performed in August 2018 using five data bases; the Cochrane library, CINAHL, EMBASE, MEDLINE, and Web of Science Collections. Inclusion criteria were: studies with adults (&gt; 18 years) with SpA, with a prescribed exercise intervention or educational programme with the aim of increasing exercise participation. Article quality was independently assessed by two assessors. Extracted descriptive data included: populations, interventions, measures of adherence and factors affecting adherence. Percentage adherence rates to prescribed exercises were calculated if not reported. Nine studies were included with a total of 658 participants, 95% of participants had a diagnosis of ankylosing spondylitis. Interventions and measurement of adherence varied, making comparisons difficult. Rates of adherence ranged from 51.4 to 95%. Single studies identified; adherence improved following educational programmes, and higher disease severity and longer diagnostic delays were associated with higher adherence. Conflicting evidence was found as to whether supervision of exercise improved adherence. Three consecutive studies demonstrated adherence reduced over time. Adherence to prescribed exercise in SpA was poorly reported and predominately for people with AS. The levels of adherence and factors affecting prescribed exercise in SpA remain unclear. Future research should measure adherence across a longer time period and investigate possible factors which may influence adherence

Exotic herbaceous species interact with severe drought to alter soil N cycling in a semi-arid shrubland

Mediterranean-type ecosystems are increasingly threatened by climate change and exotic annual species, jeopardizing the native communities and their global biodiversity. In these systems, soil nitrogen (N) limits net primary production, and its availability can be influenced by both of these stressors. To understand the interactive effects of droughts and exotic herbaceous species on soil N, we monitored the temporal variability of soil inorganic N, net N mineralization, net nitrification, and NO3- leaching under native- and exotic-dominated stands exposed to rainfall manipulation plots in a Mediterranean-type shrub-dominated community. Increasing drought severity resulted in the accumulation of soil NH4+ and NO3-, with a more pronounced increase in exotic-dominated plots. Increased net N mineralization and net nitrification and reduced leaching losses were observed as mechanisms of inorganic N accumulation. In comparison to soils under native plants, soils under exotic plants had enhanced leaching losses upon soil rewetting. We propose that distinct traits of exotic annual herbaceous species associated with higher N inputs, faster turnover, and reduced temporal uptake determine the changes in N cycling in response to droughts. Severe droughts and exotic plants may produce a larger, more vulnerable pool of N that is prone to losses while providing a competitive advantage to promote exotic growth in these N-limited ecosystems

Depth Estimation Through a Generative Model of Light Field Synthesis

Light field photography captures rich structural information that may facilitate a number of traditional image processing and computer vision tasks. A crucial ingredient in such endeavors is accurate depth recovery. We present a novel framework that allows the recovery of a high quality continuous depth map from light field data. To this end we propose a generative model of a light field that is fully parametrized by its corresponding depth map. The model allows for the integration of powerful regularization techniques such as a non-local means prior, facilitating accurate depth map estimation.Comment: German Conference on Pattern Recognition (GCPR) 201