Multivariable https://www.selleckchem.com/products/prn1371.html Firth logistic regression analysis was performed to determine predictors independently

associated with subsequent MRAB bacteremia. Results: During the study period, subsequent MRAB bacteremia was observed in 18.8% of patients (21/112). Of the 112 patients, 23 (20.5%) did not show systemic inflammatory response syndrome (SIRS). None of the 23 patients without SIRS presented with subsequent MRAB bacteremia. Multivariable logistic regression analysis showed that prior administration of carbapenems (odds ratio (OR) 7.04, 95% confidence interval (CI) 1.43-34.77) or corticosteroids (OR 6.67, 95% CI 1.19-37.44), and C-reactive protein >= 40 mg/l (OR 18.11, 95% CI 2.22-148.07) were positive predictive factors. Prior acquisition of MRAB at a site other than the catheter (OR 0.10, 95% CI 0.03-0.39) was a negative predictive factor for developing MRAB bacteremia. Conclusions: Our results suggest that patients with a CVC tip colonized with MRAB should be closely monitored

for signs and symptoms of subsequent MRAB bacteremia.”
“Background: Mycobacterium tuberculosis www.selleckchem.com/products/sbi-0206965.html (TB) is a rare cause of prosthetic joint infection. The purpose of this study was to provide an evidence-based summarization of the outcomes of TB infection after total knee arthroplasty (TKA) with a pooled analysis of the reported cases. Methods: We conducted a systematic review of published studies that have evaluated the outcomes of prosthetic knee joint infections due to TB. A structured literature review of multiple databases referenced articles from January 1950 to July 2012. Results: A total of

15 patients were identified from 13 published studies. Tuberculosis was confirmed in selleck compound all cases by histological examination and positive culture or histochemical stain/polymerase chain reaction (PCR). Treatment consisted of anti-tuberculosis medication therapy (AMT) only in 2 patients, AMT plus debridement and retention of the arthroplasty in 5 patients, and AMT plus removal/exchange of the arthroplasty in 8 patients. The average follow-up after TB infection was 29 months (range 1-96 months) and there were 3 deaths, giving a crude death rate of 0.7 per 100 person-months. At the final follow-up, the outcomes of TB infection after TKA were good except in the 3 patients who died. Conclusions: TB infection after TKA is a rare disease, however good clinical outcomes can be achieved with proper management including AMT and surgical intervention.”
“Background: The aim of this study was to better understand methicillin-resistant Staphylococcus aureus (MRSA) at the molecular level by investigating the genotypic characteristics and evolutionary patterns of MRSA clones in Shenyang, China.

(C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Introduction: Surgeons must weigh the morbidity of lower extremity bypass (LEB) with the likelihood

of a functional outcome postoperatively. We developed a model to predict ambulation status 1 year after LEB.

Methods: We analyzed a prospective registry of 1561 LEB procedures performed for occlusive disease (2003-2005) in 1400 patients (50 surgeons, 11 hospitals). Ambulation status was assessed preoperatively, at discharge, and at 1-year by life-table analysis. Cox proportional hazards models were used to determine predictors of ambulation status 1 year postoperatively.

Results: The indication for surgery was claudication in 25% and critical limb SHP099 ischemia (CLI) in 75%. Claudicant patients had higher primary (79% vs 73%, P < .001) and secondary (87% vs 81%, P < .001) graft patency rates and were more likely to be alive and ambulatory Selleckchem URMC-099 1 year postoperatively (96% vs 81%, P < .001) than CLI patients. Amputation rates were 12% for CLI patients and 1% for claudicant patients (P < .001). All claudicant patients walked before surgery, and the 95% who survived 1 year postoperatively remained ambulatory. Preoperatively, 93% of CLI patients

were ambulatory, and 88% of the survivors at 1 year remained ambulatory. The risk of dying or being nonambulatory 1 year postoperatively was increased in

patients who were nonambulatory preoperatively (hazard ratio [HR], 1.5; 95% confidence interval [CI], 1.3-1.6; P < .0001), by increasing age of 70-79 (HR, 1.8; 95% CI, 1.2-2.6; P < .007) and 80-89 years (HR, 2.3; 95% CI, 1.5-3.7; P < .0001), by CLI (HR, 2.0; 95% CI, 1.2-3.4; P < .007), by postoperative myocardial infarction (HR, 2.5; 95% CI, 1.6-4.1; P < .001), and by major amputation (HR, 2.9; 95% CI, 2.1-4.1; P < .001). Graft thrombosis during follow-up (HR, 1.6; 95% CI, 1.1-1.8; P < .003) and living in a nursing home preoperatively (HR, 3.5; 95% CI, 1.5-7.8; P < .003) were independently associated with a higher risk of being nonambulatory at 1 year.

Conclusions. Ambulatory and independent living status are well preserved after LEB. Risk factors of age, preoperative ambulatory ability, independent living status, CLI, Tideglusib datasheet graft patency, and amputation help to predict ambulatory status 1 year postoperatively. The likelihood of death or nonambulatory status at 1 year was <5% in patients with none of these risk factors to nearly 50% in patients with three or more risk factors. These variables can be used to inform decision making about whether patients should undergo LEB. (J Vasc Surg 2009;49:1431-9.)”
“The aims of the present study were to establish if nalfurafine, a kappa opioid agonist, inhibits compulsive scratching in mice elicited by the s.c.

This study examined parents’ reports of their adult children’s problems and successes and implications for ambivalence. Participants aged 40-60 years (302 men and 331 women from different families) reported on up to 3 of their adult children (N

= 1,251). Men and women differentiated among children in ratings of problems, successes, and ambivalence. Men and not women reported greater ambivalence regarding children with more physical-emotional problems and less career success. Men and women reported find more greater ambivalence regarding children with less relationship success. Consistent with ambivalence theory, individuals feel more ambivalent regarding problematic and less successful children but men’s ambivalence appears to be more sensitive to their children’s problems and successes than women’s ambivalence.”
“OBJECTIVE: We report a unique case of a dissecting thrombosed left anterior choroidal aneurysm.

CLINICAL PRESENTATION: The aneurysm was diagnosed in a pediatric patient who presented with right-sided hemiparesis. Computed tomography, computed tomographic angiography, magnetic resonance AZD6094 order imaging, and conventional angiography studies were helpful in diagnosing the aneurysm

in this patient. Imaging was consistent with an acute infarct in the left globus pallidus.

INTERVENTION: An orbitozygomatic craniotomy was performed for surgical clipping of the aneurysm.

CONCLUSION: This case illustrates the unique appearance of a dissecting aneurysm in the anterior choroidal artery and stresses Poziotinib mouse the importance of recognizing atypical presentations of complex aneurysms

in the pediatric population.”
“In this meta-analytic review of 31 laboratory studies, we examined if relatively older adults showed lower or higher cardiovascular reactivity compared with relatively younger adults. Results revealed that age was associated with lower heart rate reactivity but higher systolic blood pressure (SBP) reactivity during emotionally evocative tasks. Consistent with the predictions of dynamic integration theory, the result for SBP was moderated by the degree of task activation. These data are discussed in light of existing self-regulatory models and important future research directions.”
“The effects of advanced age and cognitive resources on the course of skill acquisition are unclear, and discrepancies among studies may reflect limitations of data analytic approaches. We applied a multilevel negative exponential model to skill acquisition data from 80 trials (four 20-trial blocks) of a pursuit rotor task administered to healthy adults (19-80 years old). The analyses conducted at the single-trial level indicated that the negative exponential function described performance well. Learning parameters correlated with measures of task-relevant cognitive resources on all blocks except the last and with age on all blocks after the second.

(C) 2012 Elsevier Ltd. All rights reserved.”
“Ejaculates contain sperm but also seminal fluid, which is increasingly recognized to be of central importance for reproductive success. However, a detailed biochemical composition and physiological understanding of seminal fluid is still elusive. We have used MS to identify the 57 most abundant proteins within the ejaculated seminal fluid of the honeybee Apis mellifiera. Their amino acid sequences revealed OTX015 nmr the presence of diverse functional categories of enzymes, regulators and structural

proteins. A number have known or predicted roles in maintaining sperm viability, protecting sperm from microbial infections or interacting with the physiology of the female. A range of putative glycoproteins or glycosylation enzymes were detected among the 57, subsequent fluorescent staining of glycolysation revealed several prominant glycoproteins in seminal fluid, while no glycoproteins were detected in sperm samples. Many of the abundant proteins that accumulate in the seminal fluid did not contain predictable tags for secretion for the cell. Comparison of the honeybee seminal fluid proteins with Drosophila seminal fluid

proteins (including selleck chemical secreted accessory gland proteins known as ACPs), and with the human seminal fluid proteome revealed the bee protein set contains a range of newly identified seminal fluid proteins and we noted more similarity of the bee protein set with the current human seminal fluid protein set than with the known Drosophila seminal fluid proteins. The honeybee seminal Liproxstatin-1 in vivo fluid proteome thus represents an important addition to available data for comparative studies of seminal fluid proteomes in insects.”
“Background/Aims: The study examined the interdependent effects of shear stress and different leukocyte subpopulations on endothelial cell activation and cell interactions during low flow and reperfusion. Methods: Human umbilical venous endothelial

cells were perfused with either neutrophils or monocytes at different shear stress (2-0.25 dyn/cm(2)) and adhesion was quantified by microscopy. Effects of adherent neutrophils and monocytes on endothelial cell adhesion molecule expression were analyzed by flow cytometry after 4-hour static coincubation. After coincubation, the cocultures were reperfused with labeled neutrophils at 2 dyn/cm(2) and their adhesion was quantified selectively. For the control, endothelium monocultures with and without lipopolysaccharide activation were used. Results: At 2 dyn/cm(2), adhesion did not exceed baseline levels on nonactivatedendothelium. Decreasing shear stress to 0.25 dyn/cm(2) largely increased the adhesion of both leukocyte subpopulations, similar to the effect of lipopolysaccharide at 2 dyn/cm(2).

This trial is registered with ClinicalTrials.gov, number NCT00540449.

Findings SB202190 research buy 346 patients were randomly assigned to receive rilpivirine and 344 to receive efavirenz and received at least one dose of study drug, with

287 (83%) and 285 (83%) in the respective groups having a confirmed response at week 48. The point estimate from a logistic regression model for the percentage difference in response was -0.4 (95% CI -5.9 to 5.2), confirming non-inferiority with a 12% margin (primary endpoint). The incidence of virological failures was 13% (rilpivirine) versus 6% (efavirenz; 11% vs 4% by ITT-TLOVR). Grade 2-4 adverse events (55 [16%] on rilpivirine vs 108 [31%] on efavirenz, p<0.0001), discontinuations due to adverse events (eight [2%] on rilpivirine vs 27 [8%] on efavirenz), rash, dizziness, and abnormal dreams or nightmares were more common with efavirenz. Increases in plasma

lipids were significantly lower with rilpivirine.

Interpretation Rilpivirine showed non-inferior efficacy compared with efavirenz, with a higher virological-failure rate, but a more favourable safety https://www.selleckchem.com/products/ldn193189.html and tolerability profile.”
“Flagella are the chief organelles of motility in bacteria. In recent years, several new findings have illuminated the evolution of bacterial flagella, including cut-down versions of the organelle in Buchnera, a dispensable ATPase and structural evidence for homology between FliG (a component of the flagellar motor) and MgtE (a magnesium transporter). However, a fresh examination of the phylogenetic distribution of flagellar genes warns against a simplistic model of early flagellar evolution.”
“The central auditory system consists of the lemniscal and nonlemniscal systems. The thalamic lemniscal and nonlemniscal auditory nuclei are different

from each other SCH772984 manufacturer in response properties and neural connectivities. The cortical auditory areas receiving the projections from these thalamic nuclei interact with each other through corticocortical projections and project down to the subcortical auditory nuclei. This corticofugal (descending) system forms multiple feedback loops with the ascending system. The corticocortical and corticofugal projections modulate auditory signal processing and play an essential role in the plasticity of the auditory system. Focal electric stimulation – comparable to repetitive tonal stimulation – of the lemniscal system evokes three major types of changes in the physiological properties, such as the tuning to specific values of acoustic parameters of cortical and subcortical auditory neurons through different combinations of facilitation and inhibition. For such changes, a neuromodulator, acetylcholine, plays an essential role. Electric stimulation of the nonlemniscal system evokes changes in the lemniscal system that is different from those evoked by the lemniscal stimulation.

Results: The most ideal pseudotumor models were created from a mixture of gelatin, Metamucil (R) and methylene blue (metagel) or from Kromopan (R) hydrocolloid. We created 33 tumors 0.5 to 3.5 cm in size (mean 2.8). All

tumors were a solid palpable mass on gross examination and ultrasonography revealed clearly visible hyperechoic lesions in 30 of 33. A renal vein tumor pseudothrombus model was successfully created in 3 pigs. We successfully performed robotic excision of pseudotumors, including partial nephrectomy for 16 and radical nephrectomy with renal vein thrombectomy for 3. Percutaneous needle core biopsy under ultrasound guidance was also successfully performed.

Conclusions: We describe what is to our knowledge a novel technique of creating solid renal tumors and tumor thrombi that can be used for training in minimally invasive kidney surgery.”
“Natural Cell Cycle inhibitor antisense transcripts and overlapping sense transcripts are expressed in a variety of tissues, including adult mouse brain. Here we show that a subset of mRNA-like sense-antisense transcript pairs are co-expressed within synaptoneurosomes of adult mouse forebrain, a subcellular fraction that is enriched click here in pinched-off dendritic spines of pyramidal neurons. Several of these pairs involve mRNAs that have been implicated in synaptic functions and in Alzheimer disease pathways. This study provides evidence that a new class of noncoding

RNAs (natural antisense transcripts) are expressed near synapses, and encourages further studies of their roles in neuronal function. (C) 2008 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.”
“Purpose: WAVE1 belongs to the Wiskott-Aldrich

syndrome family of proteins, which have an integral part in cell motility, a crucial step in cancer metastasis. We investigated the expression pattern and the effects of manipulating endogenous WAVE1 expression in prostate cancer cells.

Materials and Methods: WAVE1 protein expression in normal and cancer specimens, and in prostate cell lines was assessed using immunohistochemistry and reverse transcriptase-polymerase chain reaction, respectively. Hammerhead IWR1 ribozyme transgenes were synthesized and cloned into the mammalian expression vector pEF6/V5-His TOPO TA, and transfected by electroporation into PC-3(Delta W1R1/2) and DU-145(Delta W1R1/2) cell lines. In vitro invasion, adhesion and growth assays were used to assess the impact of WAVE1 knockdown.

Results: Immunohistochemistry of prostate tissue specimens showed that the cytoplasm of cancer cells had stronger staining than normal epithelium. Reverse transcriptase-polymerase chain reaction for WAVE1 showed strong expression in the PC-3 (European Collection of Cell Cultures, Salisbury, United Kingdom) and DU-145 (ATCC (R)) cell lines. WAVE1 knockdown was associated with a significant decrease in invasion but not in adhesion. The mean +/- SEM number of invading PC-3(Delta W1R1) and PC-3(Delta W1R2) cells was 7.27 +/- 0.

Conclusions: GA treatment decreases blood pressure and proteinuria in diabetic mice and may thus prove beneficial in diabetic nephropathy. Copyright (c) 2012 S. Karger AG, Basel”
“The PA28 complexes (also termed REG or 11S complexes) are described as activators of the 20S proteasome,

a major intracellular protease in eukaryotic cells. They bind to the ends of the barrel-shaped 20S proteasome, and activate its peptidase activities. The interferon gamma inducible PA28 alpha beta, made of the two related subunits PA28 alpha and beta, is under sustained investigation as it plays important roles in the production by the proteasome of class I Y-27632 datasheet antigen peptides. However, in vitro studies of this complex have been impaired by the difficulty of producing large amount of this protein, mainly due to the poor solubility of its beta subunit when expressed in Escherichia coli. Here we describe the construction of a bicistronic vector, allowing simultaneous production of functional human PA28 alpha and beta subunits in E. coli. Co-expression of the two proteins allows

SN-38 order efficient formation of active PA28 alpha beta complexes, that remain soluble and can be easily purified by regular chromatographic procedures. (C) 2008 Elsevier Inc. All rights reserved.”
“Bacteriophages are viruses of bacteria that are used for controlling bacterial food-borne pathogens and have been proposed for more extensive usage in infection control. Protists are now recognised to harbour viruses and virus-like particles. We propose that investigation of their prevalence in parasites be intensified. We also propose

that such viruses might be considered for virotherapy to control certain parasite infections of man and animals.”
“The effect of nicotine exposure on the subsequent self-administration of amphetamine, extinction of this behavior, and amphetamine-induced reinstatement of drug seeking was assessed with particular attention to the contribution of contextual tuclazepam stimuli paired or unpaired with nicotine during exposure. Rats were exposed to five injections, one injection every third day, of either saline or nicotine (0.4 mg/kg, P. base) in three experiments. In one, exposure injections were administered in the home cage. In another, they were administered in the self-administration chambers with the levers retracted. In a third, nicotine was administered either explicitly paired or unpaired with the self-administration chambers using a discrimination learning procedure. Starting 13-15 days later, rats were trained to self-administer amphetamine (100 mu g/kg/infusion, IV), tested under a progressive ratio (PR) schedule for 6 days, subjected to up to 20 days of extinction training, and were then tested for reinstatement by non-contingent injections of amphetamine (0, 0.2, 0.4, and 0.75 mg/kg, IP).

APP-BP1 expression was increased in the dentate gyrus of the hippocampus and in the subventricular zone of rats exposed to focal transient cerebral ischemia. In addition, APP-BP1 immunoreactivity Ilomastat overlapped

with antidoublecortin and anti-5-bromo-2deoxyuridine labeling. Focal transient cerebral ischemia has been reported earlier to induce neurogenesis in adult brains. The upregulation of APP-BP1 expression in neural progenitor cells after focal transient ischemia suggests that this protein contributes to the neurogenesis induced by transient ischemia and reperfusion. NeuroReport 22:200-205 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.”
“Purpose: Few groups have examined health related quality of life for adolescents with bladder exstrophy-epispadias. We studied parent reported health related quality of life for adolescents with bladder exstrophy-epispadias using the Child Health Questionnaire-Parent Form 50.

Materials and Methods: We recruited 11 to 17-year-old participants with bladder exstrophy-epispadias and their parents. Parents served as proxy respondents for the adolescents by self-administering a validated generic Bleomycin mw health related quality of life instrument, the Child Health Questionnaire-Parent Form 50. We collected urinary incontinence, catheterization status, and medical and

surgical history data. Mean questionnaire scores were compared to population based norms.

Results:

Median age of the 55 patients was 14 years, 69% were male and 84% were white. Diagnoses included bladder exstrophy in 48 cases and epispadias in 7. Of the participants 29 (53%) reported urinary incontinence. The median number of lifetime surgeries was 9. Although physical and psychosocial summary measure scores were comparable to norms, Selleckchem SRT1720 the mean general health perception score was significantly worse than that of a population based sample (65.8 points, 95% CI 61.4-70.2 vs 73, 95% CI 71.3-74.7, p = 0.004). Mean family activity and parent emotional impact scores were also significantly worse than in a population based sample (83.6 points, 95% CI 79.3-88.0 vs 89.7, 95% CI 87.9-91.5, p = 0.02 and 67.7, 95% CI 61.9-73.6 vs 80.3, 95% CI 78.4-82.2, p < 0.0001, respectively). Comparison of incontinent to continent children revealed a lower mean score on the parent emotional impact scale (62.6 points, 95% CI 55.5-69.8 vs 73.4, 95% CI 63.9-82.9), which approached significance (p = 0.06).

Conclusions: Although overall adolescent quality of life was comparable to norms, parents reported significantly impaired adolescent general health and family activity as well as a negative parental emotional impact. Further research is needed to identify interventions that can decrease the adverse impact of bladder exstrophy-epispadias on family activity and parent emotional distress.

Data were collected retrospectively from the Danish Vascular Registry (Karbase), the National Population Registry, and the National Inpatient Registry. The groups were analyzed for the incidences of MI, stroke, and death, with up to 20 years of follow-up.

Results: AAA patients had an annual MI incidence of 2.5% selleck chemicals (hazard ratio, 2.1;

95% confidence interval [CI], 1.9-2.2) compared with the general population. The annual incidence of stroke was 2.9% (hazard ratio, 1.8; 95% CI, 1.6-1.9), and there was a 2.4-fold (95% CI, 2.3-2.4) increase in the hazard of all-cause mortality compared with the general population.

Conclusion: AAA patients of both sexes have a high risk of atherosclerotic events (MI, stroke) and death, so lifelong prophylaxis must be considered from our epidemiologic data. Randomized

trials investigating the potential benefit of aspirin and statin therapy in AAA patients are needed. (J Vase Surg 2012;55:311-7.)”
“Rho is an essential ATP-dependant homohexameric helicase that is found in the vast majority of bacterial species. It is responsible for transcription termination at factor-dependent www.selleckchem.com/products/dmh1.html terminators. Rho binds to a specific region of the newly-synthesised mRNA and translocates along the chain until it reaches and disassembles the transcription complex. Basically,

two crystallographic structures of Rho hexamer from Escherichia coli have been reported: an open ring with RNA (or ssDNA) bound to the RNA-binding domain, and a closed ring with the RNA bound to both the RNA-binding domain and the ATP-ase domain. The structure of the protein free from RNA is these still unknown, but thermophilic bacteria enable an alternative approach to its characterization as their proteins often crystallize more easily than those of their mesophilic homologs. We report here the heterologous expression in E. coli of full-length Rho from the thermophile Thermotoga maritima, a simple protocol for the purification of its hexameric nucleic acid-free form, and the obtainment of 2.4 angstrom-diffracting crystals. (C) 2009 Elsevier Inc. All rights reserved.”
“Advances in the understanding of the endogenous cannabinoid system have led to several therapeutic indications for new classes of compounds that enhance cannabinergic responses. Endocannabinoid levels are elevated during pathogenic conditions, and inhibitors of endocannabinoid inactivation promote such on-demand responses. The endocannabinoids anandamide and 2-arachidonoyl glycerol have been implicated in protective signaling against excitotoxic episodes, including seizures.

Patient demographics, pre- and post-procedure ankle-brachial indices (ABI), and H 89 clinical trial anatomic factors (including categorization by TASC 11 classification, lesion length, and runoff vessel status) were analyzed. Outcomes evaluated included freedom from restenoses, freedom from re-intervention, overall patency, and assisted-patency.

Results: A total of 237 total limbs

were treated during the period reviewed. The study group included 108 TASC B and 32 TASC C limbs in 125 patients (mean age 73.1 +/- 10.4 years, male sex: 59%). Seventy-one percent of patients were Rutherford classification 2/3 while the remaining 29% were Rutherford classification 4/5. Mean follow-tip period was 12.7 months (range, 1-52 in). Forty-one (41) limbs experienced AZD1208 datasheet restenosis or occlusion at a mean time of 8 months (range, 1-24 in). Freedom

front restenosis/occlusion was 58.9% at 12 months and 47.9% at 24 months. Predictors of restenosis included a preoperative ABI < 0.5 (hazard ratio [HR] 3.05, 95% confidence interval [CI] 1.36-6.86, P = .007) and hypercholesterolemia (HR 2.42, 95% Cl 1.11-5.25, P = .025). Lesion length as a Continuous variable (per centimeter) also correlated with a higher risk of restenosis (HR 1.06, 95% CI 1.00-1.12, P = .057). The overall assisted-primary and secondary-patency rates were 87% and 94% respectively at 3 years with no significant differences between TASC B and TASC C limbs.

Conclusion: Endovascular interventions for TASC I I B and C lesions are associated with restenosis/occlusion rates that

are at least as good as those of open femoropopliteal bypass surgery from historical, previously published series. Furthermore, overall assisted-patency rates are excellent, although low preoperative ABIs continue to be associated with worse outcomes.”
“The use of deep brain stimulation (DBS) as an effective clinical therapy for a number of neurological disorders has been greatly hindered by the lack of understanding of the mechanisms which underlie the observed clinical improvement in patients. This problem is confounded by the difficulty of investigating the neuronal effects of DBS in situ, and the impossibility of measuring the induced current in vivo. In our recent computational work using a quasi-static finite element Olopatadine (FEM) model we have quantitatively shown that the properties of the depth electrode-brain interface (EBI) have a significant effect on the electric field induced in the brain volume surrounding the DBS electrode. In the present work, we explore the influence of the reactivity of the EBI on the crossing electric current using the Fourier-FEM approach to allow the investigation of waveform attenuation in the time domain. Results showed that the EBI affected the waveform shaping differently at different post-implantation stages, and that this in turn had implications on induced current distribution across the EBI.