Abstract
The Fermi-LAT (Large Area Telescope) collaboration recently published deep upper limits to the gamma-ray emission of the Coma cluster, a cluster hosting the prototype of giant radio haloes. ...In this paper, we extend previous studies and use a formalism that combines particle reacceleration by turbulence and the generation of secondary particles in the intracluster medium to constrain relativistic protons and their role for the origin of the radio halo. We conclude that a pure hadronic origin of the halo is clearly disfavoured as it would require excessively large magnetic fields. However, secondary particles can still generate the observed radio emission if they are reaccelerated. For the first time the deep gamma-ray limits allow us to derive meaningful constraints if the halo is generated during phases of reacceleration of relativistic protons and their secondaries by cluster-scale turbulence. In this paper, we explore a relevant range of parameter space of reacceleration models of secondaries. Within this parameter space, a fraction of model configurations is already ruled out by current gamma-ray limits, including the cases that assume weak magnetic fields in the cluster core, B ≤ 2–3 μG. Interestingly, we also find that the flux predicted by a large fraction of model configurations assuming magnetic fields consistent with Faraday rotation measures (RMs) is not far from the limits. This suggests that a detection of gamma-rays from the cluster might be possible in the near future, provided that the electrons generating the radio halo are secondaries reaccelerated and the magnetic field in the cluster is consistent with that inferred from RM.
Relative growth rates (RGR), doubling times (DT) and relative weekly yields (RY) of 39 clones (ecotypes) from 13 species representing all five genera of duckweeds were determined under standardised ...cultivation conditions. RGR ranged overall from 0.153 to 0.519 day−1, DT from 1.34 to 4.54 days and RY from 2.9 to 37.8 week−1. The RGR and RY data can be compared directly to other published findings to only a limited extent on account of missing clonal designations for and limited accessibility to previously investigated clones, as well as the use of different data denominators. However, they are consistent with the published results of other comparative duckweed studies of similar scope in showing that RGR does not vary primarily at the level of the genus or species, but rather reflects the adaptation of individual clones to specific local conditions. The RGR data support the widely held assumption that duckweeds can grow faster than other higher plants and that they can thus surpass land‐based agricultural crops in productivity. Duckweeds are highly promising for the production of biomass for nutrition and energy, but extensive clonal comparison will be required to identify the most suitable isolates for this purpose.
Giant radio halos are megaparsec-scale diffuse radio sources associated with the central regions of galaxy clusters. The most promising scenario to explain the origin of these sources is that of ...turbulent re-acceleration, in which MeV electrons injected throughout the formation history of galaxy clusters are accelerated to higher energies by turbulent motions mostly induced by cluster mergers. In this Letter, we use the amplitude of density fluctuations in the intracluster medium as a proxy for the turbulent velocity and apply this technique to a sample of 51 clusters with available radio data. Our results indicate a segregation in the turbulent velocity of radio halo and radio quiet clusters, with the turbulent velocity of the former being on average higher by about a factor of two. The velocity dispersion recovered with this technique correlates with the measured radio power through the relation , which implies that the radio power is nearly proportional to the turbulent energy rate. In case turbulence cascades without being dissipated down to the particle acceleration scales, our results provide an observational confirmation of a key prediction of the turbulent re-acceleration model and possibly shed light on the origin of radio halos.
The economic burden of Clostridium difficile McGlone, S.M.; Bailey, R.R.; Zimmer, S.M. ...
Clinical microbiology and infection,
March 2012, Volume:
18, Issue:
3
Journal Article
Peer reviewed
Open access
Although Clostridium difficile (C. difficile) is the leading cause of infectious diarrhoea in hospitalized patients, the economic burden of this major nosocomial pathogen for hospitals, third-party ...payers and society remains unclear. We developed an economic computer simulation model to determine the costs attributable to healthcare-acquired C. difficile infection (CDI) from the hospital, third-party payer and societal perspectives. Sensitivity analyses explored the effects of varying the cost of hospitalization, C. difficile-attributable length of stay, and the probability of initial and secondary recurrences. The median cost of a case ranged from $9179 to $11 456 from the hospital perspective, $8932 to $11 679 from the third-party payor perspective, and $13 310 to $16 464 from the societal perspective. Most of the costs incurred were accrued during a patient's primary CDI episode. Hospitals with an incidence of 4.1 CDI cases per 100 000 discharges would incur costs ≥$3.2 million (hospital perspective); an incidence of 10.5 would lead to costs ≥$30.6 million. Our model suggests that the annual US economic burden of CDI would be ≥$496 million (hospital perspective), ≥$547 million (third-party payer perspective) and ≥$796 million (societal perspective). Our results show that C. difficile infection is indeed costly, not only to third-party payers and the hospital, but to society as well. These results are consistent with current literature citing C. difficile as a costly disease.
Background. Whether vancomycin resistance is independently associated with mortality among patients with enterococcal bloodstream infection (BSI) is controversial. To address this issue, we performed ...a systematic literature review with meta-analysis. Methods. Data sources were studies identified using the MEDLINE database (for articles from 1988 through March 2003), the Cochrane Library (for articles published up to March 2003), and bibliographies of identified articles. Inclusion criteria were that the study assessed mortality after enterococcal BSI, compared mortality after vancomycin-resistant enterococci (VRE) BSI with that after vancomycin-susceptible enterococci (VSE) BSI, and adjusted for severity of illness. Study exclusion criteria were as follows: no report of the adjusted measure of effect (adjusted odds ratio OR, adjusted hazard ratio, or adjusted relative risk) of vancomycin resistance on mortality available and/or its adjusted 95% confidence interval (95% CI). Data in the tables, figures, or text were independently extracted by 2 of the authors. Individual weights were calculated using the 95% CI of the adjusted measures of effect performing both fixed-effect and random-effects models. Results. Nine studies were eligible (11 studies met the inclusion criteria, and 2 were excluded), with a total of 1614 enterococcal BSI episodes (683 VRE episodes and 931 VSE episodes). Patients with bacteremia caused by VRE were more likely to die than were those with VSE bacteremia (summary OR, 2.52; 95% CI, 1.9–3.4). Conclusions. Vancomycin resistance is independently associated with increased mortality among patients with enterococcal bloodstream infection.
CXCL1, a functional murine orthologue of the human chemokine CXCL8 (IL-8), and its CXCR1 and CXCR2 receptors were investigated in a murine model of acquired epilepsy developing following status ...epilepticus (SE) induced by intra-amygdala kainate. CXCL8 and its receptors were also studied in human temporal lobe epilepsy (TLE). The functional involvement of the chemokine in seizure generation and neuronal cell loss was assessed in mice using reparixin (formerly referred to as repertaxin), a non-competitive allosteric inhibitor of CXCR1/2 receptors.
We found a significant increase in hippocampal CXCL1 level within 24 h of SE onset that lasted for at least 1 week. No changes were measured in blood. In analogy with human TLE, immunohistochemistry in epileptic mice showed that CXCL1 and its two receptors were increased in hippocampal neuronal cells. Additional expression of these molecules was found in glia in human TLE.
Mice were treated with reparixin or vehicle during SE and for additional 6 days thereafter, using subcutaneous osmotic minipumps. Drug-treated mice showed a faster SE decay, a reduced incidence of acute symptomatic seizures during 48 h post-SE, and a delayed time to spontaneous seizures onset compared to vehicle controls. Upon reparixin discontinuation, mice developed spontaneous seizures similar to vehicle mice, as shown by EEG monitoring at 14 days and 2.5 months post-SE. In the same epileptic mice, reparixin reduced neuronal cell loss in the hippocampus vs vehicle-injected mice, as assessed by Nissl staining at completion of EEG monitoring.
Reparixin administration for 2 weeks in mice with established chronic seizures, reduced by 2-fold on average seizure number vs pre-treatment baseline, and this effect was reversible upon drug discontinuation. No significant changes in seizure number were measured in vehicle-injected epileptic mice that were EEG monitored in parallel.
Data show that CXCL1-IL-8 signaling is activated in experimental and human epilepsy and contributes to acute and chronic seizures in mice, therefore representing a potential new target to attain anti-ictogenic effects.
•CXCL1 is increased in mouse brain and not in blood during acute and chronic seizures.•CXCL1/IL-8 and their receptors are induced in neurons and glia in epileptic mice and human TLE.•Reparixin by inhibiting CXCR1/2 receptors reduces seizures and neuronal loss in mice.•CXCL1/IL-8 signaling represents a potential new target to attain anti-ictogenic effects.
The safety and efficacy of the Woven EndoBridge (WEB) device has been shown in multiple good clinical practice trials, whereas aneurysm locations in these trials were restricted to bifurcation ...aneurysms located at the circle of Willis (MCA bifurcation, ICA bifurcation, anterior communicating artery, basilar artery tip). Our aim was to evaluate angiographic and clinical results with the WEB 17 in aneurysm locations that were excluded from the good clinical practice trials, assuming that the angiographic and clinical results are similar to those of the good clinical practice trials for aneurysms in traditional locations.
We performed retrospective analysis of immediate and follow-up results of aneurysms in locations outside the good clinical practice trials in which the WEB 17 was used on an intention-to-treat approach.
Between June 2017 and May 2020, forty-seven aneurysms in 44 patients met the inclusion criteria. Aneurysm locations were the ICA posterior communicating artery in 19 (40.3%), the ICA paraophthalmic or choroidal locations in 4 (8.6%), anterior cerebral artery A2 segment in 13 (27.7%), MCA M1 segment in 2 (4.3%), posterior cerebral artery P2 segment in 2 (4.3%), PICA in 3 (6.4%), and the superior cerebellar artery in 4 (8.4%) cases. The procedure-related morbidity and mortality rates in the entire series were 0.0%. The early and late (<12 and >12 months) complete occlusion rates were 63.9% (23/36) and 77.8% (14/18), respectively.
The WEB 17 is safe and effective in aneurysm locations different from the traditional bifurcation aneurysms included in the good clinical practice trials. Further studies will help to define the entire spectrum of aneurysm morphologies and locations suitable for the WEB 17.
Background
Brain metastases (BrM) incidence is 25% to 50% in women with advanced human epidermal growth factor receptor 2 (HER2)‐positive breast cancer. Radiation and surgery are currently the main ...local treatment approaches for central nervous system (CNS) metastases. Systemic anti‐HER2 therapy following a diagnosis of BrM improves outcomes. Previous preclinical data has helped elucidate HER2 brain trophism, the blood‐brain/blood‐tumor barrier(s), and the brain tumor microenvironment, all of which can lead to development of novel therapeutic options.
Recent findings
Several anti‐HER2 agents are currently available and reviewed here, some of which have recently shown promising effects in BrM patients, specifically. New strategies driven by and focusing on brain metastasis‐specific genomics, immunotherapy, and preventive strategies have shown promising results and are under development.
Conclusions
The field of HER2+ breast cancer, particularly for BrM, continues to evolve as new therapeutic strategies show promising results in recent clinical trials. Increasing inclusion of patients with BrM in clinical studies, and a focus on assessing their outcomes both intracranially and extracranially, is changing the landscape for patients with HER2+ CNS metastases by demonstrating the ability of newer agents to improve outcomes.
The economic impact of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) remains unclear. We developed an economic simulation model to quantify the costs associated with ...CA-MRSA infection from the societal and third-party payer perspectives. A single CA-MRSA case costs third-party payers $2277–$3200 and society $7070–$20 489, depending on patient age. In the United States (US), CA-MRSA imposes an annual burden of $478 million to 2.2 billion on third-party payers and $1.4–13.8 billion on society, depending on the CA-MRSA definitions and incidences. The US jail system and Army may be experiencing annual total costs of $7–11 million ($6–10 million direct medical costs) and $15–36 million ($14–32 million direct costs), respectively. Hospitalization rates and mortality are important cost drivers. CA-MRSA confers a substantial economic burden on third-party payers and society, with CA-MRSA-attributable productivity losses being major contributors to the total societal economic burden. Although decreasing transmission and infection incidence would decrease costs, even if transmission were to continue at present levels, early identification and appropriate treatment of CA-MRSA infections before they progress could save considerable costs.
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