The younger the animal’s age at the time of exposure, the more si

The younger the animal’s age at the time of exposure, the more significant the effect on later MWM performance. Compared to the neonates, animals exposed at P7W were relatively insensitive to sevoflurane: memory was impaired in this group only after repeated exposures to low doses or single exposures to high doses. Early life exposure to click here sevoflurane can result in spatial memory impairments in adulthood and the shorter the interval between exposures, the greater the deficit. (C) 2013 Elsevier Inc. All rights reserved.”
“Purpose: We generated extensive transcriptional and proteomic profiles from a Her2-driven mouse model

of breast cancer that closely recapitulates human breast cancer. This report makes these data publicly available in raw and processed forms, as a resource to the community. Importantly, we previously made biospecimens from this same mouse model freely available through a sample repository, so researchers GDC-941 can obtain samples to test biological hypotheses without the need of breeding animals and collecting biospecimens.

Experimental design:

Twelve datasets are available, encompassing 841 LC-MS/MS experiments (plasma and tissues) and 255 microarray analyses of multiple tissues (thymus, spleen, liver, blood cells, and breast). Cases and controls were rigorously paired to avoid bias.

Results: In total, 18 880 unique peptides were identified (PeptideProphet peptide Carnitine palmitoyltransferase II error rate <= 1%), with 3884 and 1659 non-redundant protein groups identified in plasma and tissue datasets, respectively. Sixty-one of these protein groups overlapped between cancer plasma and cancer tissue.

Conclusions and clinical relevance: These data are of use for advancing our understanding of cancer biology, for software and quality control

tool development, investigations of analytical variation in MS/MS data, and selection of proteotypic peptides for multiple reaction monitoring-MS. The availability of these datasets will contribute positively to clinical proteomics.”
“Objectives. Guided by the transtheoretical model of health behavior change, this study sought to explain why (a) rates of advance care planning remain low in the general population and (b) surrogate decision makers are often inaccurate about patients’ end-of-life preferences.

Methods. The study used quantitative data from a cross-sectional internet survey conducted between July and October 2010. The 2,150 participants aged 18-64 belonged to 1,075 married or cohabiting heterosexual couples. Participants included members of a nationally representative internet panel and a convenience sample from online advertisements.

Results. Older age was associated with a greater likelihood of having executed a living will and/or appointed a durable power of attorney for health care. Both older age and poorer health were independently associated with a greater likelihood of having discussed end-of-life health care treatment preferences.

While some authors support dopamine metabolism/oxidation inside 5

While some authors support dopamine metabolism/oxidation inside 5-hydroxytryptamine PD-1/PD-L1 inhibitor (5-HT) terminals as the key factor responsible for ROS formation and final 5-HT terminal degeneration, others believe

it is MDMA metabolism into pro-oxidant compounds. Although at first sight both hypotheses appear to contend with each other, it may not be the case. This mini-review was therefore undertaken to try to reconcile both hypotheses and to address the dilemma of the causality of MDMA neurotoxicity. Copyright (C) 2009 S. Karger AG, Basel”
“Objectives: In patients having mitral valve surgery, concomitant surgery for mild functional tricuspid regurgitation remains the subject of debate. This study examined the effect of Maze operation and tricuspid valve repair on postoperative functional tricuspid regurgitation progression.


The study retrospectively analyzed 250 patients (86 men, 164 women) with mild functional tricuspid regurgitation (grade 2) who had mitral valve surgery between January 1994 and July 2006. Based on follow-up data, patients were defined as either stable (n = 209, 83.6%) or aggravated (n 41, 16.4%). Predictors for significant tricuspid regurgitation development were identified using Cox regression analysis.

Results: ASP2215 manufacturer The mean follow-up time was 62.6 +/- 39.8 months after surgery. Although most mitral valve procedures were successful, there was an increase in the incidence of significant functional tricuspid regurgitation overall from immediately postoperative to final assessment (5.2% to 16.4%, P< 0.01). Univariate analysis showed that old age, shorter aortic crossclamping time, and omission of Maze operation were associated with functional tricuspid regurgitation

progression. Multivariate analysis showed that older age (adjusted hazard ratio, 1.05; 95% confidence interval, 1.02 to 1.08), a rheumatic etiology of the mitral valve disease (adjusted hazard ratio, 2.31; 95% confidence interval, 1.21 to 4.42), and no Maze operation (adjusted hazard ratio, 7.90; 95% confidence interval, 1.90 to 32.86) were independent predictors of Lck mild functional tricuspid regurgitation progression. For the 168 patients with preoperative atrial fibrillation, Maze operation improved the tricuspid regurgitation -free survival significantly (P<. 01) but tricuspid valve repair showed no significant difference.

Conclusions: Mild functional tricuspid regurgitation can progress postoperatively despite successful mitral valve surgery. Although tricuspid valve repairs alleviate progression of functional tricuspid regurgitation, concomitant Maze operation is a more powerful protective factor against mild functional tricuspid regurgitation progression.

(C) 2010 IBRO Published by Elsevier Ltd All rights reserved “

(C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Heterosexual transmission of human immunodeficiency virus

(HIV-1) is the predominant mode of infection worldwide. However, the early steps of transepithelial infection still need to be clarified. Using epithelial cells, originating from the female genital tract, and peripheral blood mononuclear cells as subepithelial target cells, an in vitro dual-chamber model of the female genital tract was developed. Remarkably, an intact layer of some cell types (HEC-1A, CaSki and Ect1) served as a protective barrier against cell-free but not against cell-associated HIV-1 that crossed the epithelial barrier through transmigration.

Furthermore, dysfunctions of the epithelial layers FHPI research buy were assessed by monitoring transepithelial Selonsertib clinical trial electric resistance and transepithelial passage of FluoSpheres(R) and HIV-1 after treatment with nonoxynol-9 (N-9). Most of the functional assays showed dysfunction of the epithelial barrier at lower concentrations compared to a widely used colorimetric toxicity assay (WST-1). Finally, N-9 treatment caused a significant increase in the production of interleukin-8 (IL-8) and macrophage inflammatory protein-3 alpha (MIP-3 alpha) and a decrease of Secretory Leukocyte Protease Inhibitor (SLPI) and Monocyte Chemotactic Protein-1 (MCP-1) in this model. In conclusion, this model is a useful tool to (1) study HIV-1 transmission mechanisms and (2) evaluate epithelial toxicity

of candidate microbicides. (C) 2010 Elsevier BM. All rights reserved.”
“Schlager inbred hypertensive mice (BPH/2J) have been suggested to have high blood pressure (BP) due to an overactive sympathetic nervous system (SNS). Tryptophan synthase The brain nuclei associated with the hypertension are also those involved in the integration of the cardiovascular responses to stress. Therefore, in the present study, we hypothesize that BPH/2J mice likely have a greater response to stress that is associated with greater neuronal activation in the limbic system, hypothalamus and medulla in regions known to regulate sympathetic activity. Male hypertensive BPH/2J and normotensive BPN/3J mice were implanted with telemetry devices and exposed to dirty cage-switch, an acute model of aversive stress. Stress exposure caused a 60% greater pressor response in BPH/2J compared with BPN/3J mice and an increase in activity, by contrast the level of tachycardia was less in BPH/2J mice.

“Positive affect was examined as a predictor of (1) cardi

“Positive affect was examined as a predictor of (1) cardiovascular reactivity during a sadness and an anger recall task and recovery following the protocol, (2) epinephrine (EPI) and norepinephrine (NOREPI) reactivity LY2606368 price and level during the recall protocol, and (3) the diurnal pattern of salivary cortisol. Sample was 328 individuals. Negative affect, age, race, sex, smoking status, income, and BMI were adjusted. During sadness recall, positive affect was inversely related

to systolic blood pressure (p = .007) and diastolic blood pressure (p = .049) reactivity, and unrelated to heart rate (p = .226). Positive affect was unrelated to reactivity during anger recall (ps>.19), and was unrelated to recovery selleck screening library at the end of the recall protocol. Positive affect was inversely

related to the mean level of NOREPI (p = .046), and unrelated to EPI (p = .149). Positive affect was inversely related to the increase in cortisol 30 min post awakening (p = .042), and unrelated to the evening decline in cortisol levels (p = .174). Positive emotions may be relevant to good health.”
“The honeybee Apis mellifera has emerged as a robust and influential model for the study of classical conditioning, thanks to the existence of a powerful Pavlovian conditioning protocol, the olfactory conditioning of the proboscis extension response (PER). In 2011, the olfactory PER conditioning protocol celebrates 50 years since it was first introduced by Kimihisa Takeda in 1961. Here, we review its origins, developments, and perspectives in order to define future research avenues and necessary methodological and conceptual evolutions. We show that olfactory PER conditioning has become a versatile tool for the study of questions in extremely diverse fields in addition to the study of learning and memory and that it has allowed behavioral characterizations, not only of honeybees, but also of other insect species, for which

the protocol was adapted. We celebrate, therefore, Takeda’s original work and prompt colleagues to conceive and establish further robust behavioral tools for an accurate characterization of insect learning and memory at multiple levels of analysis.”

Some copy-number variants are associated with genomic disorders with extreme phenotypic heterogeneity. The cause of this variation is unknown, Interleukin-3 receptor which presents challenges in genetic diagnosis, counseling, and management.


We analyzed the genomes of 2312 children known to carry a copy- number variant associated with intellectual disability and congenital abnormalities, using array comparative genomic hybridization.


Among the affected children, 10.1% carried a second large copy-number variant in addition to the primary genetic lesion. We identified seven genomic disorders, each defined by a specific copy-number variant, in which the affected children were more likely to carry multiple copy-number variants than were controls.

(C) 2012 Elsevier Ltd All rights reserved “
“Our previous s

(C) 2012 Elsevier Ltd. All rights reserved.”
“Our previous studies in rats have shown that the adipocyte-derived hormone leptin induces antidepressant-like effects with a behavioral profile similar to selective serotonin reuptake inhibitor (SSRI) C646 manufacturer antidepressants. Acute SSRI treatment causes paradoxical anxiogenic responses, although chronic treatment has therapeutic effects on anxiety. However, the role of leptin in anxiety remains to be established.

The scope of this study was to investigate the acute effects of leptin on anxiety-related behaviors in comparison with the SSRI antidepressant


Adult male C57BL/6J mice received intraperitoneal injection of leptin or fluoxetine. Thirty minutes after injection, mice were subjected to the tail suspension test (TST) and forced swim test (FST) for evaluating antidepressant activity. Anxiety-like behavior was assessed in the elevated plus maze (EPM), social interaction, and open field tests 30 min following drug treatment.

While leptin and fluoxetine showed similar antidepressant-like behavioral effects in the TST and FST, they differed in the behavioral assays for anxiety. Open arm exploration in the EPM was increased

by leptin but decreased by fluoxetine. Analysis of social interaction revealed that distinct social behavioral components were modulated by leptin and fluoxetine. The total time of active social behaviors was increased by leptin but reduced by fluoxetine. In addition, self-grooming, a non-social behavior, was suppressed by leptin treatment. Neither leptin see more nor fluoxetine produced significant effects in the open field test.

In contrast to anxiogenic-like effects induced by acute 5-Fluoracil price fluoxetine, leptin elicits anxiolytic-like effects after acute administration. These results suggest that leptin has both antidepressant-like and anxiolytic-like properties.”
“Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by selective loss of motor neurons which leads to progressive

paralysis and death by respiratory failure. Although the cause of sporadic ALS is still unknown, oxidative stress is suggested to play a major role in the pathogenesis of this disease and of the rare familial form, which often exhibits mutations of the superoxide dismutase 1 (SOD1) gene. Since enhanced iron levels are discussed to participate in oxidative stress and neuronal death, we analyzed the expression levels of Fe-related mRNAs in a cell culture ALS model with the G93A mutation of SOD1.

We observed an increased total iron content in G93A-SOD1 SH-SY5Y neuroblastoma cells compared to wild-type (WT)-SOD1 cells. mRNA expression for transferrin receptor 1 (TfR1) and divalent metal transporter 1 was increased in G93A-SOD1 cells, which was in accordance with higher iron uptake.

Previous results identified a domain in the major capsid scaffold

Previous results identified a domain in the major capsid scaffold protein, ICP35, required for interaction with pU,6 and its incorporation into capsids formed in vitro (G. P. Singer et al.,

J. Virol. 74:6838-6848, 2005). In the current studies, PU(L)6 and scaffold proteins were found to coimmunoprecipitate from lysates of both HSV-infected cells and mammalian cells expressing scaffold proteins and PU(L)6. The coimmunoprecipitation of PU(L)6 and scaffold proteins was precluded upon deletion of codons 143 to 151 within U(L)26.5, encoding ICP35. While wild-type scaffold proteins colocalized with PU(L)6 when transiently coexpressed as viewed by indirect immunofluorescence, deletion of UL26.5 codons 143 to 151 precluded this colocalization. A recombinant herpes simplex virus, vJB11, was generated that lacked U(L)26.5 codons 143 to 151. A virus derived from C646 this mutant but bearing a restored U(L)26.5 was also generated. vJBI1 was unable to cleave or package viral DNA, whereas the restored virus packaged DNA normally. vJBI1 produced ample numbers of B capsids in infected cells, but these lacked normal levels of pU(L)6. The deletion in U(L)26.5 also rendered PU(L)6 resistant to detergent extraction from

vJ1311-infected cells. These data indicate that, as was observed in vitro, amino acids 143 to 151 of ICP35 are critical for (i) interaction between scaffold proteins and PU(L)6 and (ii) incorporation of the HSV portal into capsids.”
“In the rat, a number of sensory modalities converge in the perirhinal cortex (PC). 4-Aminobutyrate aminotransferase The neural pathway from the perirhinal cortex to AZD1152 order the entorhinal cortex (EC) is considered one of the main routes into the entorhinal-hippocampal network. Evidence accumulated recently suggests that EC and PC, far from being passive relay stations, actively gate impulse traffic between neocortex and hippocampus. Using slice

preparation maintaining the neurocircuit connecting PC, EC, hippocampal formation and amygdala, we investigated the associative function of PC and EC with respect to sensory and motivational stimuli and the influence of the association on the neurocircuit. In horizontal slices located ventrally to the rhinal sulcus, where we stimulated area 35 and the lateral amygdala, both inputs can be independently conveyed to the dentate gyrus. In slightly more dorsal slices where we stimulated area 36 and the lateral amygdala, the coincidence of the two inputs was needed to activate the hippocampus. This need for association of the two inputs was apparently mediated by the deep layer of EC. In all instances activation of the deep layers of EC was sufficient to activate the dentate gyrus, suggesting the relevance of the deep layers in cortico-hippocampal interactions. (c) 2008 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

SCNX rats also exhibited an upregulation of the PER1 peak in hypo

SCNX rats also exhibited an upregulation of the PER1 peak in hypothalamic structures, especially in the dorsomedial hypothalamic nucleus (DMH), while in some limbic structures PERI rhythmicity was dampened. The present results indicate that the SCN participates actively during food entrainment modulating the response of hypothalamic and corticolimbic structures, resulting in an increased anticipatory response. (C) 2010 IBRO. Published

by Elsevier Ltd. All rights reserved.”
“Influenza-associated encephalopathy (IAE) is characterized by severe neurological complications during high-grade fever with high Selleckchem Alisertib morbidity and mortality in children. The major neurological complications during high-grade fever include convulsive seizures, loss of consciousness, neuropsychiatric

behavior (hallucination, meaningless speech, disorientation, laughing alone); high voltage amplitude slow waves and the occurrence of theta oscillation are depicted on the electroencephalogram (EEG) in the IAE patients. At the early phase of the disease, the cytokines levels increase in severe cases. To understand the neuronal properties in the CNS leading to these neurological complications in IAE patients, we recorded EEG signals from the hippocampus and cortex of rats infected with influenza A/WSN/33 BYL719 molecular weight H1N1 virus (IAV) strain. Abnormal EEG activities were observed in all infected rats under anesthesia, including high voltage EEG burst amplitude and increased EEG spikes in the early phase (8 h-day 2) of infection, and these increases at the early phase were in parallel with a significant increase level of interleukin-6 (IL-6) in the serum. When the infected rats were heat-stressed by elevating the rat body core temperature to 39-41 degrees C, these abnormal EEG activities were enhanced, and the oscillation pattern shifted in most of rats from slow bursting waves (<1 Hz) to theta oscillation (3-6 Hz). These results indicate that the abnormal EEG activities in IAE patients could be well reproduced in anesthetized IAV infected

rats under hyperthermia, hence this animal model will be useful for further understandings the mechanism of neuronal complications Clomifene in IAE patient during high-grade fever. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Brain injury is associated with neuroinflammation, neurodegeneration, and also blood coagulation with thrombin formation and generation of activated protein C (APC). We have previously shown that APC, a serine protease of hemostasis, at very low concentrations has protective effects in rat hippocampal and cortical neurons at glutamate-induced excitotoxicity through protease-activated receptor-1 (PAR-1) or endothelial receptor of protein C (EPCR)/PAR-1. The transcription factor nuclear factor kappa B (NF-kappa B) takes part in regulating neuronal survival in several pathological conditions.

40 +/- 0 03), PC (0 51 +/- 0 06, 0 52 +/- 0 06), fornix (0 37 +/-

40 +/- 0.03), PC (0.51 +/- 0.06, 0.52 +/- 0.06), fornix (0.37 +/- 0.06, 0.38 +/- 0.06), CST (0.70 +/- 0.06, 0.69 +/- 0.07), and MD values for

UF (0.81 +/- 0.03, 0.82 +/- 0.04), PC (0.72 +/- 0.03, 0.72 +/- 0.04), fornix (1.86 +/- 0.32, 1.94 +/- 0.37), and CST (0.72 +/- 0.03, 0.74 +/- 0.04). We identified a significant positive correlation between age and MD in the right UF and bilateral fornices, and a negative correlation between age and FA in bilateral fornices. Hemispheric asymmetry was observed in FA of UF (right > left) and MD of CST (left > right).

The results constitute a normative dataset for diffusion parameters of four WM tracts that can be used to identify, characterize, and establish the significance learn more of changes in diseases affecting specific tracts.”
“Purpose: There is debate

in the literature on the role of high grade prostatic intraepithelial neoplasia as a risk factor for subsequent prostatic adenocarcinoma detection on prostatic needle biopsy. We determined whether high grade prostatic intraepithelial neoplasia on initial prostatic needle biopsy is an independent risk factor for prostatic adenocarcinoma and whether differences exist between prostatic adenocarcinoma in patients with previous high grade prostatic intraepithelial neoplasia and those with a benign diagnosis.

Materials and Methods: Pathological findings in prostatic needle biopsies in 12,304 men who underwent initial prostatic needle biopsy in an 8-year period were analyzed. Patients were included in the analysis when the initial diagnosis was high grade prostatic intraepithelial neoplasia alone or a benign Gemcitabine diagnosis and at least 1 followup prostatic needle biopsy was performed. The primary study outcome was prostatic adenocarcinoma and secondary outcome measurements

were cancer characteristics, BCKDHB such as Gleason score and extent of tissue involvement with prostatic adenocarcinoma.

Results: In the high grade prostatic intraepithelial neoplasia group of 564 patients and the benign group of 845, 27.48% and 22.01%, respectively, were diagnosed with prostatic adenocarcinoma on followup prostatic needle biopsy (p = 0.02). When age, prostate specific antigen and sampling extent were adjusted for, the adenocarcinoma risk after an initial diagnosis of high grade prostatic intraepithelial neoplasia remained significant (OR 1.38, p = 0.03). The risk was related to the extent of high grade prostatic intraepithelial neoplasia in the initial sample with a greater likelihood of adenocarcinoma when multiple prostatic sites were involved by high grade prostatic intraepithelial neoplasia. Patients in whom prostatic adenocarcinoma developed after a benign diagnosis on initial prostatic needle biopsy had greater tumor volume. However, mean followup was longer in the benign group than in the high grade prostatic intraepithelial neoplasia group (2.35 vs 1.36 years).

5 cm in diameter were excluded from analysis Patients with prior

5 cm in diameter were excluded from analysis. Patients with prior abdominal aortic aneurysm repair were not excluded.

Results. Fifty-six patients (96% male; mean age, 72 +/- 10 years) had either open (n = 24) or endovascular (n = 32) Ulixertinib manufacturer repair with median follow-up of 36 months. Seven patients were treated for rupture, six with open repair, and one with an endograft. Average aneurysm size for patients in the open and endovascular repair cohorts was 4.5 +/- 2.4 cm and 4.0 +/- 1.1 cm, respectively (P = .35). One episode of endograft limb thrombosis at five months was treated with catheter-directed thrombolytic

therapy and stent placement. Thirty-day mortality for patients undergoing elective and emergent open repair was 1/18 (6%) and 1/6 (17%), respectively. There was no 30-day mortality for the endovascular group. Median length of stay was 10.5 days in the open group and one day in the endovascular elective group (P < .01). There was no mid-term, aneurysm-related mortality in either group. Primary patency rates were similar between the open and endovascular groups at five years (100% vs. 96%, P = .07). Aneurysm sac diameter decreased in 67% (21/28) of patients that underwent endovascular repair. One patient with a Type III endoleak required relining of the endograft with a P second endograft at 72 months.


These data demonstrate that in appropriately selected patients, endovascular repair of isolated iliac artery aneurysms is a safe, effective alternative to open repair with mid-term follow-up. Endovascular repair is associated with a significantly CH5183284 concentration reduced hospital length of stay and may be associated with decreased need for transfusion and mortality when compared with open repair. (J Vase Surg 2009;49:1147-53.)”
“Background: Cardiac troponin testing is central

to the diagnosis Morin Hydrate of acute myocardial infarction. We evaluated a sensitive troponin I assay for the early diagnosis and risk stratification of myocardial infarction.

Methods: In a multicenter study, we determined levels of troponin I as assessed by a sensitive assay, troponin T, and traditional myocardial necrosis markers in 1818 consecutive patients with suspected acute myocardial infarction, on admission and 3 hours and 6 hours after admission.

Results: For samples obtained on admission, the diagnostic accuracy was highest with the sensitive troponin I assay (area under the receiver-operating-characteristic curve [AUC], 0.96), as compared with the troponin T assay (AUC, 0.85) and traditional myocardial necrosis markers. With the use of the sensitive troponin I assay (cutoff value, 0.04 ng per milliliter) on admission, the clinical sensitivity was 90.7%, and the specificity was 90.2%. The diagnostic accuracy was virtually identical in baseline and serial samples, regardless of the time of chest-pain onset.

It is a core process in the choice of specific defenses, such as

It is a core process in the choice of specific defenses, such as flight, freezing, defensive threat and defensive attack, that counter the threat and minimize the danger it poses. This highly adaptive process takes into account important characteristics, such as type and location (including distance from the subject)

of the threat, as well as those (e.g. presence of an escape route or hiding place) of the situation, combining them to predict which specific defense is optimal with selleck inhibitor that particular combination of threat and situation. Risk assessment is particularly associated with ambiguity either of the threat stimulus or of the outcome of available defensive behaviors. It is also crucial in determining that threat is no longer present, permitting a return to normal, nondefensive behavior. Although risk assessment has been described in detail in rodents, it is also a feature of human defensive

behavior, particularly in association with ambiguity. Rumination may be a specifically human form of risk assessment, more often expressed by women, and highly associated with anxiety.

Risk assessment behaviors respond to drugs effective against generalized anxiety disorder; however, flight, a dominant specific defense in many common situations, shows a pharmacological response profile closer to that of panic disorder. Risk assessment and flight also appear to show some consistent selleckchem differences in terms of brain regional activation patterns, suggesting a potential biological

differentiation of NADPH-cytochrome-c2 reductase anxiety and fear/panic systems. An especially intriguing possibility is that mirror neurons may respond to some of the same types of situational differences that are analyzed during risk assessment, suggesting an additional functional role for these neurons. (C) 2010 Published by Elsevier Ltd.”
“The relationship between virus evolution and recombination in species B human enteroviruses was investigated through large-scale genetic analysis of echovirus type 9 (E9) and E11 isolates (n = 85 and 116) from 16 European, African, and Asian countries between 1995 and 2008. Cluster 1 E9 isolates and genotype D5 and A E11 isolates showed evidence of frequent recombination between the VP1 and 3Dpol regions, the latter falling into 23 (E9) and 43 (E11) clades interspersed phylogenetically with 46 3Dpol clades of E30 and with those of other species B serotypes. Remarkably, only 2 of the 112 3Dpol clades were shared by more than one serotype (E11 and E30), demonstrating an extremely large and genetically heterogeneous recombination pool of species B nonstructural-region variants. The likelihood of recombination increased with geographical separation and time, and both were correlated with VP1 divergence, whose substitution rates allowed recombination half-lives of 1.3, 9.8, and 3.1 years, respectively, for E9, E11, and E30 to be calculated.