The stealth episome: suppression of gene expression on the excised genomic island PPHGI-1 from Pseudomonas syringae pv. phaseolicola

Pseudomonas syringae pv. phaseolicola is the causative agent of halo blight in the common bean, Phaseolus vulgaris. P. syringae pv. phaseolicola race 4 strain 1302A contains the avirulence gene avrPphB (syn. hopAR1), which resides on PPHGI-1, a 106 kb genomic island. Loss of PPHGI-1 from P. syringae pv. phaseolicola 1302A following exposure to the hypersensitive resistance response (HR) leads to the evolution of strains with altered virulence. Here we have used fluorescent protein reporter systems to gain insight into the mobility of PPHGI-1. Confocal imaging of dual-labelled P. syringae pv. phaseolicola 1302A strain, F532 (dsRFP in chromosome and eGFP in PPHGI-1), revealed loss of PPHGI-1::eGFP encoded fluorescence during plant infection and when grown in vitro on extracted leaf apoplastic fluids. Fluorescence-activated cell sorting (FACS) of fluorescent and non-fluorescent PPHGI-1::eGFP F532 populations showed that cells lost fluorescence not only when the GI was deleted, but also when it had excised and was present as a circular episome. In addition to reduced expression of eGFP, quantitative PCR on sub-populations separated by FACS showed that transcription of other genes on PPHGI-1 (avrPphB and xerC) was also greatly reduced in F532 cells harbouring the excised PPHGI-1::eGFP episome. Our results show how virulence determinants located on mobile pathogenicity islands may be hidden from detection by host surveillance systems through the suppression of gene expression in the episomal state

Coastally Trapped Wind Reversals: Progress toward Understanding

Coastally trapped wind reversals along the U.S. west coast, which are often accompanied by a northward surge of fog or stratus, are an important warm-season forecast problem due to their impact on coastal maritime activities and airport operations. Previous studies identified several possible dynamic mechanisms that could be responsible for producing these events, yet observational and modeling limitations at the time left these competing interpretations open for debate. In an effort to improve our physical understanding, and ultimately the prediction, of these events, the Office of Naval Research sponsored an Accelerated Research Initiative in Coastal Meteorology during the years 1993â 98 to study these and other related coastal meteorological phenomena. This effort included two field programs to study coastally trapped disturbances as well as numerous modeling studies to explore key dynamic mechanisms. This paper describes the various efforts that occurred under this program to provide an advancement in our understanding of these disturbances. While not all issues have been solved, the synoptic and mesoscale aspects of these events are considerably better understood.Most of the authors were supported through the Office of Naval Research Coastal Meteorology Accelerated Research Initiative, one of the authors (WTT) was supported by Program Element 0601153N, Naval Research Laboratory

Geographic Differences in Time to Culture Conversion in Liquid Media: Tuberculosis Trials Consortium Study 28. Culture Conversion Is Delayed in Africa

Tuberculosis Trials Consortium Study 28, was a double blind, randomized, placebo-controlled, phase 2 clinical trial examining smear positive pulmonary Mycobacterium tuberculosis. Over the course of intensive phase therapy, patients from African sites had substantially delayed and lower rates of culture conversion to negative in liquid media compared to non-African patients. We explored potential explanations of this finding.In TBTC Study 28, protocol-correct patients (n = 328) provided spot sputum specimens for M. tuberculosis culture in liquid media, at baseline and weeks 2, 4, 6 and 8 of study therapy. We compared sputum culture conversion for African and non-African patients stratified by four baseline measures of disease severity: AFB smear quantification, extent of disease on chest radiograph, cavity size and the number of days to detection of M. tuberculosis in liquid media using the Kaplan-Meier product-limit method. We evaluated specimen processing and culture procedures used at 29 study laboratories serving 27 sites.African TB patients had more extensive disease at enrollment than non-African patients. However, African patients with the least disease by the 4 measures of disease severity had conversion rates on liquid media that were substantially lower than conversion rates in non-African patients with the greatest extent of disease. HIV infection, smoking and diabetes did not explain delayed conversion in Africa. Some inter-site variation in laboratory processing and culture procedures within accepted practice for clinical diagnostic laboratories was found.Compared with patients from non-African sites, African patients being treated for TB had delayed sputum culture conversion and lower sputum conversion rates in liquid media that were not explained by baseline severity of disease, HIV status, age, smoking, diabetes or race. Further investigation is warranted into whether modest variation in laboratory processes substantially influences the efficacy outcomes of phase 2 TB treatment trials or if other factors (e.g., nutrition, host response) are involved.ClinicalTrials.gov NCT00144417

Coastally Trapped Wind Reversals: Progress toward Understanding

Coastally trapped wind reversals along the U.S. west coast, which are often accompanied by a northward surge of fog or stratus, are an important warm-season forecast problem due to their impact on coastal maritime activities and airport operations. Previous studies identified several possible dynamic mechanisms that could be responsible for producing these events, yet observational and modeling limitations at the time left these competing interpretations open for debate. In an effort to improve our physical understanding, and ultimately the prediction, of these events, the Office of Naval Research sponsored an Accelerated Research Initiative in Coastal Meteorology during the years 1993-98 to study these and other related coastal meteorological phenomena. This effort included two field programs to study coastally trapped disturbances as well as numerous modeling studies to explore key dynamic mechanisms. This paper describes the various efforts that occurred under this program to provide an advancement in our understanding of these disturbances. While not all issues have been solved, the synoptic and mesoscale aspects of these events are considerably better understood

Highlights of Coastal Waves 1996

Highlights of Coastal Waves 199

Pitch Comparisons between Electrical Stimulation of a Cochlear Implant and Acoustic Stimuli Presented to a Normal-hearing Contralateral Ear

Four cochlear implant users, having normal hearing in the unimplanted ear, compared the pitches of electrical and acoustic stimuli presented to the two ears. Comparisons were between 1,031-pps pulse trains and pure tones or between 12 and 25-pps electric pulse trains and bandpass-filtered acoustic pulse trains of the same rate. Three methods—pitch adjustment, constant stimuli, and interleaved adaptive procedures—were used. For all methods, we showed that the results can be strongly influenced by non-sensory biases arising from the range of acoustic stimuli presented, and proposed a series of checks that should be made to alert the experimenter to those biases. We then showed that the results of comparisons that survived these checks do not deviate consistently from the predictions of a widely-used cochlear frequency-to-place formula or of a computational cochlear model. We also demonstrate that substantial range effects occur with other widely used experimental methods, even for normal-hearing listeners

Mycobacterium tuberculosis bloodstream infection prevalence, diagnosis, and mortality risk in seriously ill adults with HIV: a systematic review and meta-analysis of individual patient data.

BACKGROUND: The clinical and epidemiological significance of HIV-associated Mycobacterium tuberculosis bloodstream infection (BSI) is incompletely understood. We hypothesised that M tuberculosis BSI prevalence has been underestimated, that it independently predicts death, and that sputum Xpert MTB/RIF has suboptimal diagnostic yield for M tuberculosis BSI. METHODS: We did a systematic review and individual patient data (IPD) meta-analysis of studies performing routine mycobacterial blood culture in a prospectively defined patient population of people with HIV aged 13 years or older. Studies were identified through searching PubMed and Scopus up to Nov 10, 2018, without language or date restrictions and through manual review of reference lists. Risk of bias in the included studies was assessed with an adapted QUADAS-2 framework. IPD were requested for all identified studies and subject to harmonised inclusion criteria: age 13 years or older, HIV positivity, available CD4 cell count, a valid mycobacterial blood culture result (excluding patients with missing data from lost or contaminated blood cultures), and meeting WHO definitions for suspected tuberculosis (presence of screening symptom). Predicted probabilities of M tuberculosis BSI from mixed-effects modelling were used to estimate prevalence. Estimates of diagnostic yield of sputum testing with Xpert (or culture if Xpert was unavailable) and of urine lipoarabinomannan (LAM) testing for M tuberculosis BSI were obtained by two-level random-effect meta-analysis. Estimates of mortality associated with M tuberculosis BSI were obtained by mixed-effect Cox proportional-hazard modelling and of effect of treatment delay on mortality by propensity-score analysis. This study is registered with PROSPERO, number 42016050022. FINDINGS: We identified 23 datasets for inclusion (20 published and three unpublished at time of search) and obtained IPD from 20, representing 96·2% of eligible IPD. Risk of bias for the included studies was assessed to be generally low except for on the patient selection domain, which was moderate in most studies. 5751 patients met harmonised IPD-level inclusion criteria. Technical factors such as number of blood cultures done, timing of blood cultures relative to blood sampling, and patient factors such as inpatient setting and CD4 cell count, explained significant heterogeneity between primary studies. The predicted probability of M tuberculosis BSI in hospital inpatients with HIV-associated tuberculosis, WHO danger signs, and a CD4 count of 76 cells per μL (the median for the cohort) was 45% (95% CI 38-52). The diagnostic yield of sputum in patients with M tuberculosis BSI was 77% (95% CI 63-87), increasing to 89% (80-94) when combined with urine LAM testing. Presence of M tuberculosis BSI compared with its absence in patients with HIV-associated tuberculosis increased risk of death before 30 days (adjusted hazard ratio 2·48, 95% CI 2·05-3·08) but not after 30 days (1·25, 0·84-2·49). In a propensity-score matched cohort of participants with HIV-associated tuberculosis (n=630), mortality increased in patients with M tuberculosis BSI who had a delay in anti-tuberculosis treatment of longer than 4 days compared with those who had no delay (odds ratio 3·15, 95% CI 1·16-8·84). INTERPRETATION: In critically ill adults with HIV-tuberculosis, M tuberculosis BSI is a frequent manifestation of tuberculosis and predicts mortality within 30 days. Improved diagnostic yield in patients with M tuberculosis BSI could be achieved through combined use of sputum Xpert and urine LAM. Anti-tuberculosis treatment delay might increase the risk of mortality in these patients. FUNDING: This study was supported by Wellcome fellowships 109105Z/15/A and 105165/Z/14/A

Coastally trapped wind reversals : progress toward understanding

Coastally trapped wind reversals along the U.S. west coast, which are often accompanied by a northward surge of fog or stratus, are an important warm—season forecast problem due to their impact on coastal maritime activities and airport operations. Previous studies identified several possible dynamic mechanisms that could be responsible for producing these events, yet observational and modeling limitations at the time left these competing interpretations open for debate. In an effort to improve our physical understanding, and ultimately the prediction, of these events, the Office of Naval Research sponsored an Accelerated Research Initiative in Coastal Meteorology during the years 1993—98 to study these and other related coastal meteorological phenomena. This effort included two field programs to study coastally trapped disturbances as well as numerous modeling studies to explore key dynamic mechanisms. This paper describes the various efforts that occurred under this program to provide an advancement in our understanding of these disturbances. While not all issues have been solved, the synoptic and mesoscale aspects of these events are considerably better understood

Nomenclature for kidney function and disease: report of a Kidney Disease:Improving Global Outcomes (KDIGO) Consensus Conference

The worldwide burden of kidney disease is rising, but public awareness remains limited, underscoring the need for more effective communication by stakeholders in the kidney health community. Despite this need for clarity, the nomenclature for describing kidney function and disease lacks uniformity. In June 2019, Kidney Disease: Improving Global Outcomes (KDIGO) convened a Consensus Conference with the goal of standardizing and refining the nomenclature used in the English language to describe kidney function and disease, and of developing a glossary that could be used in scientific publications. Guiding principles of the conference were that the revised nomenclature should be patient-centered, precise, and consistent with nomenclature used in the KDIGO guidelines. Conference attendees reached general consensus on the following recommendations: (i) to use "kidney" rather than "renal" or "nephro-" when referring to kidney disease and kidney function; (ii) to use "kidney failure" with appropriate descriptions of presence or absence of symptoms, signs, and treatment, rather than "end-stage kidney disease"; (iii) to use the KDIGO definition and classification of acute kidney diseases and disorders (AKD) and acute kidney injury (AKI), rather than alternative descriptions, to define and classify severity of AKD and AKI; (iv) to use the KDIGO definition and classification of chronic kidney disease (CKD) rather than alternative descriptions to define and classify severity of CKD; and (v) to use specific kidney measures, such as albuminuria or decreased glomerular filtration rate (GFR), rather than "abnormal" or "reduced" kidney function to describe alterations in kidney structure and function. A proposed 5-part glossary contains specific items for which there was general agreement. Conference attendees acknowledged limitations of the recommendations and glossary, but they considered standardization of scientific nomenclature to be essential for improving communication