Percutaneous needle biopsy for indeterminate renal masses: a national survey of UK consultant urologists

<p>Abstract</p> <p>Background</p> <p>The use of percutaneous needle biopsy in the evaluation of indeterminate renal masses is controversial and its role in management remains largely unclear. We set to establish current practice on this issue in UK urology departments.</p> <p>Methods</p> <p>We conducted a national questionnaire survey of all consultant urologists in the UK, to establish current practice and attitudes towards percutaneous needle biopsy in the management of indeterminate renal masses.</p> <p>Results</p> <p>139 (43%) consultant urologists never use biopsy, whereas 111 (34%) always employ it for the diagnosis of indeterminate renal masses. 75 (23%) urologists use biopsy only for a selected patient group. Mass in a solitary kidney, bilateral renal masses and a past history of non-renal cancer were the main indications for use of percutaneous biopsy. The risk of false negative results and biopsy not changing the eventual management of their patients were the commonest reasons not to perform biopsy.</p> <p>Conclusion</p> <p>There is a wide and varied practice amongst UK Consultant Urologists in the use of percutaneous biopsy as part of the management of indeterminate renal masses. The majority of urologists believe biopsy confers no benefit. However there is a need to clarify this issue in the wake of recent published evidence as biopsy results may provide critical information for patients with renal masses in a significant majority. It not only differentiates benign from malignant tissue but can also help in deciding the management option for patients undergoing minimally invasive treatments.</p

A Web-based Intervention for Abused Women: The New Zealand Isafe Randomised Controlled Trial Protocol

Background: Intimate partner violence (IPV) and its associated negative mental health consequences are significant for women in New Zealand and internationally. One of the most widely recommended interventions is safety planning. However, few women experiencing violence access specialist services for safety planning. A safety decision aid, weighing the dangers of leaving or staying in an abusive relationship, gives women the opportunity to prioritise, plan and take action to increase safety for themselves and their children. This randomised controlled trial is testing the effectiveness of an innovative, interactive web-based safety decision aid. The trial is an international collaborative concurrent replication of a USA trial (IRIS study NCT01312103), regionalised for the Aotearoa New Zealand culture and offers fully automated online trial recruitment, eligibility screening and consent. Methods/Design: In a fully automated web-based trial (isafe) 340 abused women will be randomly assigned in equal numbers to a safety decision aid intervention or usual safety planning control website. Intervention components include: (a) safety priority setting, (b) danger assessment and (c) an individually tailored safety action plan. Self-reported outcome measures are collected at baseline and 3, 6, and 12-months post-baseline. Primary outcomes are depression (measured by Center for Epidemiologic Studies Depression Scale, Revised) and IPV exposure (measured by Severity Violence Against Women Scale) at 12 months post-baseline. Secondary outcomes include PTSD, psychological abuse, decisional conflict, safety behaviors and danger in the relationship. Discussion: This trial will provide much-needed information on the potential relationships mong safety planning, improved mental health, reduced violence as well as decreased decisional conflict related to safety in the abusive relationship. The novel web-based safety decision aid intervention may provide a cost-effective, easily accessed safety-planning resource that can be translated into clinical and community practice by multiple health disciplines and advocates. The trial will also provide information about how women in abusive relationships safely access safety information and resources through the Internet. Finally, the trial will inform other research teams on the feasibility and acceptability of fully automated recruitment, eligibility screening, consent and retention procedures. Trial registration: Trial registered on 03 July 2012 on the Australian New Zealand Clinical Trials Registry ACTRN12612000708853

Using machine learning to build temperature-based ozone parameterizations for climate sensitivity simulations

A number of studies have demonstrated the importance of ozone in climate change simulations, for example concerning global warming projections and atmospheric dynamics. However, fully interactive atmospheric chemistry schemes needed for calculating changes in ozone are computationally expensive. Climate modelers therefore often use climatological ozone fields, which are typically neither consistent with the actual climate state simulated by each model nor with the specific climate change scenario. This limitation applies in particular to standard modeling experiments such as preindustrial control or abrupt 4xCO2 climate sensitivity simulations. Here we suggest a novel method using a simple linear machine learning regression algorithm to predict ozone distributions for preindustrial and abrupt 4xCO2 simulations. Using the atmospheric temperature field as the only input, the regression reliably predicts three-dimensional ozone distributions at monthly to daily time intervals. In particular, the representation of stratospheric ozone variability is much improved compared with a fixed climatology, which is important for interactions with dynamical phenomena such as the polar vortices and the Quasi-Biennial Oscillation. Our method requires training data covering only a fraction of the usual length of simulations and thus promises to be an important stepping stone towards a range of new computationally efficient methods to consider ozone changes in long climate simulations. We highlight key development steps to further improve and extend the scope of machine learning-based ozone parameterizations

Nitrate Respiration Protects Hypoxic Mycobacterium tuberculosis Against Acid- and Reactive Nitrogen Species Stresses

There are strong evidences that Mycobacterium tuberculosis survives in a non-replicating state in the absence of oxygen in closed lesions and granuloma in vivo. In addition, M. tuberculosis is acid-resistant, allowing mycobacteria to survive in acidic, inflamed lesions. The ability of M. tuberculosis to resist to acid was recently shown to contribute to the bacillus virulence although the mechanisms involved have yet to be deciphered. In this study, we report that M. tuberculosis resistance to acid is oxygen-dependent; whereas aerobic mycobacteria were resistant to a mild acid challenge (pH 5.5) as previously reported, we found microaerophilic and hypoxic mycobacteria to be more sensitive to acid. In hypoxic conditions, mild-acidity promoted the dissipation of the protonmotive force, rapid ATP depletion and cell death. Exogenous nitrate, the most effective alternate terminal electron acceptor after molecular oxygen, protected hypoxic mycobacteria from acid stress. Nitrate-mediated resistance to acidity was not observed for a respiratory nitrate reductase NarGH knock-out mutant strain. Furthermore, we found that nitrate respiration was equally important in protecting hypoxic non-replicating mycobacteria from radical nitrogen species toxicity. Overall, these data shed light on a new role for nitrate respiration in protecting M. tuberculosis from acidity and reactive nitrogen species, two environmental stresses likely encountered by the pathogen during the course of infection

Characterizing planetary systems with SPIRou: M-dwarf planet-search survey and the multiplanet systems GJ 876 and GJ 1148

SPIRou is a near-infrared spectropolarimeter and a high-precision velocimeter. The SPIRou Legacy Survey collected data from February 2019 to June 2022, half of the time devoted to a blind search for exoplanets around nearby cool stars. The aim of this paper is to present this program and an overview of its properties, and to revisit the radial velocity (RV) data of two multiplanet systems, including new visits with SPIRou. From SPIRou data, we can extract precise RVs using efficient telluric correction and line-by-line measurement techniques, and we can reconstruct stellar magnetic fields from the collection of polarized spectra using the Zeeman-Doppler imaging method. The stellar sample of our blind search in the solar neighborhood, the observing strategy, the RV noise estimates, chromatic behavior, and current limitations of SPIRou RV measurements on bright M dwarfs are described. In addition, SPIRou data over a 2.5-year time span allow us to revisit the known multiplanet systems GJ~876 and GJ~1148. For GJ~876, the new dynamical analysis including the four planets is consistent with previous models and confirms that this system is deep in the Laplace resonance and likely chaotic. The large-scale magnetic map of GJ~876 over two consecutive observing seasons is obtained and shows a dominant dipolar field with a polar strength of 30~G, which defines the magnetic environment in which the inner planet with a period of 1.94~d is embedded. For GJ~1148, we refine the known two-planet model.Comment: accepted in A&

Central metabolism in Mycobacterium smegmatis during the transition from O2-rich to O2-poor conditions as studied by isotopomer-assisted metabolite analysis

Isotopomer-assisted metabolite analysis was used to investigate the central metabolism of Mycobacterium smegmatis and its transition from normal growth to a non-replicating state under a hypoxic environment. Tween 80 significantly promoted aerobic growth by improving O2 transfer, while only small amount was degraded and metabolized via the TCA cycle for biomass synthesis. As the bacillus encountered hypoxic stress, isotopomer analysis suggested: (1) isocitrate lyase activity increased, which further induced glyoxylate pathway and glycine dehydrogenase for replenishing NAD+; (2) the relative amount of acetyl-CoA entering the TCA cycle was doubled, whereas little entered the glycolytic and pentose phosphate pathways

The Two-Domain LysX Protein of Mycobacterium tuberculosis Is Required for Production of Lysinylated Phosphatidylglycerol and Resistance to Cationic Antimicrobial Peptides

The well-recognized phospholipids (PLs) of Mycobacterium tuberculosis (Mtb) include several acidic species such as phosphatidylglycerol (PG), cardiolipin, phosphatidylinositol and its mannoside derivatives, in addition to a single basic species, phosphatidylethanolamine. Here we demonstrate that an additional basic PL, lysinylated PG (L-PG), is a component of the PLs of Mtb H37Rv and that the lysX gene encoding the two-domain lysyl-transferase (mprF)-lysyl-tRNA synthetase (lysU) protein is responsible for L-PG production. The Mtb lysX mutant is sensitive to cationic antibiotics and peptides, shows increased association with lysosome-associated membrane protein–positive vesicles, and it exhibits altered membrane potential compared to wild type. A lysX complementing strain expressing the intact lysX gene, but not one expressing mprF alone, restored the production of L-PG and rescued the lysX mutant phenotypes, indicating that the expression of both proteins is required for LysX function. The lysX mutant also showed defective growth in mouse and guinea pig lungs and showed reduced pathology relative to wild type, indicating that LysX activity is required for full virulence. Together, our results suggest that LysX-mediated production of L-PG is necessary for the maintenance of optimal membrane integrity and for survival of the pathogen upon infection

High Content Phenotypic Cell-Based Visual Screen Identifies Mycobacterium tuberculosis Acyltrehalose-Containing Glycolipids Involved in Phagosome Remodeling

The ability of the tubercle bacillus to arrest phagosome maturation is considered one major mechanism that allows its survival within host macrophages. To identify mycobacterial genes involved in this process, we developed a high throughput phenotypic cell-based assay enabling individual sub-cellular analysis of over 11,000 Mycobacterium tuberculosis mutants. This very stringent assay makes use of fluorescent staining for intracellular acidic compartments, and automated confocal microscopy to quantitatively determine the intracellular localization of M. tuberculosis. We characterised the ten mutants that traffic most frequently into acidified compartments early after phagocytosis, suggesting that they had lost their ability to arrest phagosomal maturation. Molecular analysis of these mutants revealed mainly disruptions in genes involved in cell envelope biogenesis (fadD28), the ESX-1 secretion system (espL/Rv3880), molybdopterin biosynthesis (moaC1 and moaD1), as well as in genes from a novel locus, Rv1503c-Rv1506c. Most interestingly, the mutants in Rv1503c and Rv1506c were perturbed in the biosynthesis of acyltrehalose-containing glycolipids. Our results suggest that such glycolipids indeed play a critical role in the early intracellular fate of the tubercle bacillus. The unbiased approach developed here can be easily adapted for functional genomics study of intracellular pathogens, together with focused discovery of new anti-microbials

Optical and near-infrared stellar activity characterization of the early M dwarf Gl~205 with SOPHIE and SPIRou

The stellar activity of M dwarfs is the main limitation for discovering and characterizing exoplanets orbiting them since it induces quasi-periodic RV variations. We aim to characterize the magnetic field and stellar activity of the early, moderately active, M dwarf Gl205 in the optical and nIR domains. We obtained high-precision quasi-simultaneous spectra in the optical and nIR with the SOPHIE spectrograph and SPIRou spectropolarimeter between 2019 and 2022. We computed the RVs from both instruments and the SPIRou Stokes V profiles. We used ZDI to map the large-scale magnetic field over the time span of the observations. We studied the temporal behavior of optical and nIR RVs and activity indicators with the Lomb-Scargle periodogram and a quasi-periodic GP regression. In the nIR, we studied the equivalent width of Al I, Ti I, K I, Fe I, and He I. We modeled the activity-induced RV jitter using a multi-dimensional GP regression with activity indicators as ancillary time series. The optical and nIR RVs have similar scatter but nIR shows a more complex temporal evolution. We observe an evolution of the magnetic field topology from a poloidal dipolar field in 2019 to a dominantly toroidal field in 2022. We measured a stellar rotation period of Prot=34.4$\pm$0.5 d in the longitudinal magnetic field. Using ZDI we measure the amount of latitudinal differential rotation (DR) shearing the stellar surface yielding rotation periods of Peq=32.0$\pm$1.8 d at the stellar equator and Ppol=45.5$\pm$0.3 d at the poles. We observed inconsistencies in the activity indicators' periodicities that could be explained by these DR values. The multi-dimensional GP modeling yields an RMS of the RV residuals down to the noise level of 3 m/s for both instruments, using as ancillary time series H$\alpha$ and the BIS in the optical, and the FWHM in the nIR.Comment: 41 pages, 24 figures. Accepted for publication in A&A. Improved quality of figures and reduced size of Appendi

Diabetes Is Associated with Cerebrovascular but not Alzheimer\u27s Disease Neuropathology

INTRODUCTION: The relationship of diabetes to specific neuropathologic causes of dementia is incompletely understood. METHODS: We used logistic regression to evaluate the association between diabetes and infarcts, Braak neurofibrillary tangle stage, and neuritic plaque score in 2365 autopsied persons. In a subset of \u3e1300 persons with available cognitive data, we examined the association between diabetes and cognition using Poisson regression. RESULTS: Diabetes increased odds of brain infarcts (odds ratio [OR] = 1.57, P \u3c .0001), specifically lacunes (OR = 1.71, P \u3c .0001), but not Alzheimer\u27s disease neuropathology. Diabetes plus infarcts was associated with lower cognitive scores at end of life than infarcts or diabetes alone, and diabetes plus high level of Alzheimer\u27s neuropathologic changes was associated with lower mini-mental state examination scores than the pathology alone. DISCUSSION: This study supports the conclusions that diabetes increases the risk of cerebrovascular but not Alzheimer\u27s disease pathology, and at least some of diabetes\u27 relationship to cognitive impairment may be modified by neuropathology