Transrectal ultrasound (TRUS)—guided prostate biopsy is currently considered the standard technique for obtaining tissue to make a histological diagnosis of prostatic carcinoma. Infectious ...complications following TRUS-guided prostate biopsy are well described, and are reportedly increasing in incidence. The role of antibiotic prophylaxis in reducing post—TRUS biopsy infections is now established, and many guidelines suggest that fluoroquinolone antimicrobials are the prophylactic agents of choice. Of note, however, recent reports suggest an emerging association between TRUS biopsy and subsequent infection with fluoroquinolone-resistant Escherichia coli. Against this background, we provide an overview of the epidemiology, prevention, and treatment of infectious complications following TRUS biopsy, in the wider context of increasing global antimicrobial resistance.
The recent consensus definition for the diagnosis of fracture-related infection (FRI) includes the identification of indistinguishable microorganisms in at least 2 surgical deep-tissue specimens as a ...confirmatory criterion. However, this cut-off, and the total number of specimens from a patient with suspected FRI that should be sent for microbiological testing, have not been validated. We endeavored to estimate the accuracy of different numbers of specimens and diagnostic cut-offs for microbiological testing of deep-tissue specimens in patients undergoing surgical treatment for possible FRI.
A total of 513 surgical procedures in 385 patients with suspected FRI were included. A minimum of 2 surgical deep-tissue specimens were submitted for microbiological testing; 5 or more specimens were analyzed in 345 procedures (67%). FRI was defined by the presence of any confirmatory criteria other than microbiology. Resampling was utilized to model the sensitivity and specificity of diagnostic cut-offs for the number of surgical specimens yielding indistinguishable microorganisms and for the total number of specimens. The likelihood of detecting all clinically relevant microorganisms was also assessed.
A diagnostic cut-off of at least 2 of 5 specimens with indistinguishable microorganisms identified by culture was 68% sensitive (95% confidence interval CI, 62% to 74%) and 87% specific (95% CI, 81% to 94%) for the diagnosis of FRI. Two out of 3 specimens were 60% sensitive (95% CI, 55% to 66%) and 92% specific (95% CI, 88% to 96%). Submitting only 3 deep-tissue specimens risked missing clinically relevant microorganisms in at least 1 in 10 cases.
The present study was the first to validate microbiological criteria for the diagnosis of FRI, supporting the current confirmatory diagnostic criteria for FRI. Analysis of at least 5 deep-tissue specimens in patients with possible FRI is recommended.
Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Platelets have long been recognized to be of central importance in haemostasis, but their participation in pathological conditions such as thrombosis, atherosclerosis and inflammation is now also ...well established. The platelet has therefore become a key target in therapies to combat cardiovascular disease. Anti‐platelet therapies are used widely, but current approaches lack efficacy in a proportion of patients, and are associated with side effects including problem bleeding. In the last decade, substantial progress has been made in understanding the regulation of platelet function, including the characterization of new ligands, platelet‐specific receptors and cell signalling pathways. It is anticipated this progress will impact positively on the future innovations towards more effective and safer anti‐platelet agents. In this review, the mechanisms of platelet regulation and current anti‐platelet therapies are introduced, and strong, and some more speculative, potential candidate target molecules for future anti‐platelet drug development are discussed.
British Journal of Pharmacology (2008) 154, 918–939; doi:10.1038/bjp.2008.151; published online 21 April 2008
Abstract
Background
We evaluated the efficacy, pharmacokinetics (PK), and safety of clofazimine (CFZ) in patients living with human immunodeficiency virus (HIV) with cryptosporidiosis.
Methods
We ...performed a randomized, double-blind, placebo-controlled study. Primary outcomes in part A were reduction in Cryptosporidium shedding, safety, and PK. Primary analysis was according to protocol (ATP). Part B of the study compared CFZ PK in matched individuals living with HIV without cryptosporidiosis.
Results
Twenty part A and 10 part B participants completed the study ATP. Almost all part A participants had high viral loads and low CD4 counts, consistent with failure of antiretroviral (ARV) therapy. At study entry, the part A CFZ group had higher Cryptosporidium shedding, total stool weight, and more diarrheal episodes compared with the placebo group. Over the inpatient period, compared with those who received placebo, the CFZ group Cryptosporidium shedding increased by 2.17 log2 Cryptosporidium per gram stool (95% upper confidence limit, 3.82), total stool weight decreased by 45.3 g (P = .37), and number of diarrheal episodes increased by 2.32 (P = .87). The most frequent solicited adverse effects were diarrhea, abdominal pain, and malaise. One placebo and 3 CFZ participants died during the study. Plasma levels of CFZ in participants with cryptosporidiosis were 2-fold lower than in part B controls.
Conclusions
Our findings do not support the efficacy of CFZ for the treatment of cryptosporidiosis in a severely immunocompromised HIV population. However, this trial demonstrates a pathway to assess the therapeutic potential of drugs for cryptosporidiosis treatment. Screening persons living with HIV for diarrhea, and especially Cryptosporidium infection, may identify those failing ARV therapy.
Clinical Trials Registration
NCT03341767.
We evaluated clofazimine for treatment of adults living with human immunodeficiency virus and cryptosporidiosis. Clofazimine was well tolerated but did not reduce Cryptosporidium excretion or diarrhea compared with adults treated with placebo. This trial forms a blueprint for future cryptosporidiosis therapeutic trials.
Beam steering is essential for a variety of optical applications such as communication, LIDAR, and imaging. Microelectromechanical system (MEMS) mirrors are an effective method of achieving modest ...speeds and angular range at low cost. Typically there are a number of tradeoffs considered when designing a tip-tilt mirror, such as tilt angle and speed. For example, many mirrors are designed to scan at their resonant frequency to achieve large angles. This is effective for a scanning mode; however, this makes the device slow and ineffective as a galvo (quasi-static). Here, we present a magnetic MEMS mirror with extreme quasi-static mechanical tilt angles of ±60° (±120° optical) about two rotation axes. This micromirror enables full hemispheric optical coverage without compromising speed; settling in 4.5 ms using advanced drive techniques. This mirror will enable new applications for MEMS micromirrors previously thought impossible due to their limited angular range and speed.
ABSTRACT
We present multiwavelength temporal and spectral characteristics of a magnetic cataclysmic variable (MCV) Swift J0503.7-2819, using far ultraviolet and X-ray data from AstroSat, supplemented ...with optical data from the Southern African Large Telescope and X-ray data from the XMM-Newton and Swift observatories. The X-ray modulations at 4897.6657 s and 3932.0355 s are interpreted as the orbital (PΩ) and spin (Pω) period, respectively, and are consistent with prior reports. With a spin-orbit period ratio of 0.8 and PΩ falling below the period gap (2–3 h) of CVs, Swift J0503.7-2819 would be the newest addition to the growing population of nearly synchronous MCVs, which we call EX Hya-like systems. Hard X-ray luminosity of <2.5 × 1032 erg s−1, as measured with the Swift Burst Alert Telescope, identifies it to be a low-luminosity intermediate polar, similar to other EX Hya-like systems. The phenomenology of the light curves and the spectral characteristics rule out a purely disc-fed/stream-fed model and instead reveal the presence of complex accretion structures around the white dwarf. We propose a ring-like accretion flow, akin to EX Hya, using period ratio, stability arguments, and observational features. An attempt is made to differentiate between the asynchronous polar/nearly synchronous intermediate polar nature of Swift J0503.7-2819. Further, we note that with the advent of sensitive surveys, a growing population of MCVs that exhibit characteristics of both polars and intermediate polars is beginning to be identified, likely forming a genealogical link between the two conventional classes of MCVs.
•We used camera detections to evaluate how fishers responded to forest disturbances.•Detection rates were lower in summer, and occupancy was highest at 1640m elevation.•Occupancy trended lower after ...extensive restorative fuel reduction, or extensive burning.•Extensive restorative fuel reduction depressed local persistence by 24%.•Extractive activities were not linked to lower occupancy or reduced persistence.
Fire suppression and logging have contributed to major changes in California’s Sierra Nevada forests. Strategically placed landscape treatments (SPLATS) are being used to reduce density of trees, shrubs, and surface fuels to limit wildfire intensity and spread, but may negatively impact fishers (Pekania pennanti). We used camera traps to survey for fishers among 1-km2 grid cells of forest habitat in the Sierra National Forest, California. We used single-season (n=894 cells) and multi-season (n=361 cells) occupancy modeling to evaluate responses of fishers to fuel reduction in the 5years prior to camera surveys. We also assessed occupancy in relation to burn history, elevation, and an index of canopy cover. Camera traps detected fishers most often between 1380m and 1970m elevation, and fisher occupancy was maximized at 0.80 at 1640m elevation. Probability of detection was higher after initial fisher detection, in habitats with high canopy cover, and when surveys were done in fall to spring. Fisher occupancy was positively linked to canopy cover, and trended lower among cells with higher levels of managed burning or forest fires within 25years of surveys, and in cells where 5years of cumulative disturbance from restorative fuel reduction was higher. Local persistence declined 24% in areas with more restorative fuel reduction (0–100% of a cell), but was not diminished by prior burning, or disturbance from extractive activities (tree removals for commerce or hazard mitigation). Reduced local persistence by fishers in areas with extensive restorative fuel reduction was likely temporary; evidence from other sources intimated that they would resume higher use within a few years of ecological recovery. The trend for lower occupancy in extensively burned forest cells suggested that forest fires reduced but did not eliminate foraging opportunities for fishers. We also found that wildfires increased in frequency in our study area after the 1980s, and recent fires may increasingly impinge on higher elevation forests with higher fisher occupancy. Forest fuel reduction likely imposes a more limited short term cost to fisher habitat use than previously believed, but less is known about the responses of resting or denning fishers to management disturbance. Fuel reduction treatments could be intensified below ∼1450m elevation, which may reduce spread of fires into higher elevation forests where fishers are more common, and where denning is focused.
Large intramuscular triglyceride (IMTG) stores in sedentary, obese individuals have been linked to insulin resistance, yet well-trained athletes exhibit high IMTG levels whilst maintaining insulin ...sensitivity. Contrary to previous assumptions, it is now known that IMTG content per se does not result in insulin resistance. Rather, insulin resistance is caused, at least in part, by the presence of high concentrations of harmful lipid metabolites, such as diacylglycerols and ceramides in muscle. Several mechanistic differences between obese sedentary individuals and their highly trained counterparts have been identified, which determine the differential capacity for IMTG synthesis and breakdown in these populations. In this review, we first describe the most up-to-date mechanisms by which a low IMTG turnover rate (both breakdown and synthesis) leads to the accumulation of lipid metabolites and results in skeletal muscle insulin resistance. We then explore current and potential exercise and nutritional strategies that target IMTG turnover in sedentary obese individuals, to improve insulin sensitivity. Overall, improving IMTG turnover should be an important component of successful interventions that aim to prevent the development of insulin resistance in the ever-expanding sedentary, overweight and obese populations.
Novelty:
A description of the most up-to-date mechanisms regulating turnover of the IMTG pool.
An exploration of current and potential exercise/nutritional strategies to target and enhance IMTG turnover in obese individuals.
Overall, highlights the importance of improving IMTG turnover to prevent the development of insulin resistance.
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