The role of single-agent vinblastine and other vinca alkaloid in

The role of single-agent vinblastine and other vinca alkaloid in the management of pediatric LGGs deserves further investigation.”
“Objective. In safety studies, events reported as infections may be misclassified and, therefore, affect the validity of estimated risks associated with biologic agents. Using data from the Consortium of Rheumatology Researchers of North America (CORRONA), we evaluated hospitalized infection reports contributed by rheumatologists to establish their validity.\n\nMethods. All patients hospitalized

with infections from 2002 to 2007 reported to CORRONA were examined and compared with information from hospital discharge summaries and other confirmatory data. Infectious episodes were classified this website by two physicians as confirmed, empirically treated, possible or unlikely.\n\nResults. Of 562 reported

hospitalized infectious episodes, 9% were classified as unlikely and had minimal or no supporting evidence for infection, leaving 509 hospitalized infectious episodes. Of these, 53% of the infectious episodes were classified as confirmed, 15% empirically treated and 32% possible. The confirmation status of infectious episodes for younger or biologic-exposed participants was similar to older and biologic-unexposed participants.\n\nConclusion. More than two-thirds of hospitalized infections reported by rheumatologists were confirmed or had evidence that the physician was treating an infection.

In almost all cases, there was at least modest evidence THZ1 clinical trial for an infection. Future studies should consider case definitions for infections or sensitivity analyses, or both, regarding the certainty of an infection to account for possible misclassification and reduce bias.”
“Organic compounds have been extracted from calcium carbonate skeletons produced by three invertebrate species belonging to distinct phyla. The soluble parts of these skeleton matrices were isolated and analysed by synchrotron-based X-ray spectroscopy (XPS). The presence of calcium associated with buy Navitoclax these organic materials was revealed in every sample studied, with important variations in Ca 2p binding energy from species to species. Measured Ca 2p binding energy values are more related to compositional diversity of the mineralizing matrices of the skeletons, whose taxonomic dependence has long been established, than to the Ca carbonate polymorph selected to build the skeletal units. This suggests a physical bond between species-specific mineralizing organic assemblages and the associated calcium. Remarkably, the binding energy of 2p electrons in calcium associated with mineralizing matrices is consistently higher than Ca 2p values obtained in purely mineral carbonate (both calcite and aragonite).

05) In both the in vitro and in vivo trials, the strains demonst

05). In both the in vitro and in vivo trials, the strains demonstrated the induction of the Mx transcript, although no differences were detected, and the level always were significantly lesser that observed in poly I:C samples. The results suggest that the infectivity observed ACY-738 is related to the presence of certain specific residues in VP2, and that neither the infectivity nor the genotype

appears to bear any relation to Mx induction capacity. (C) 2011 Elsevier B.V. All rights reserved.”
“Sexual differentiation of the brain can be considered as a process during which effects of sex steroid hormones secreted during early development is maintained into adulthood. Epigenetic regulation is emerging as a potentially important mechanism of conveyance of long-lasting Mcl-1 apoptosis effects of the hormonal and environmental milieu in the developing brain. Evidence has accumulated to show that epigenetic regulation is involved in the control

of sexual differentiation of the brain. In the preoptic area (POA), which is important for male sexual behavior, histones associated with the estrogen receptor (ER) alpha and aromatase (Arom) gene promoters are differentially acetylated between the sexes, and two subtypes of histone deacetylase (HDAC2 and 4) are associated with the same promoters at higher frequencies in males in the early postnatal period. Since ER alpha and Arom are essential genes in masculinization of the brain, these findings suggest that histone deacetylation in the early postnatal period is involved in masculinization of the brain. Indeed, inhibition of HDAC activity in males during this period abrogates brain masculinization: structural sexual dimorphism of the bed nucleus of the stria terminalis is eliminated and expression of male sexual behavior is reduced in adulthood. Previous reports have demonstrated that ER alpha gene expression in the POA is higher in females during the developmental and pubertal

periods and in adulthood, indicating that sexually dimorphic click here ER alpha expression that appears in early postnatal development is maintained until adulthood by epigenetic programming. The ER alpha promoter is also more sparsely methylated in females, with an inverse correlation with ER alpha expression. In addition to the hormonal effect, the amount of maternal care received during postnatal development has a lasting effect on ER alpha expression mediated by DNA methylation of its promoter. Taken together, these results suggest that epigenetic mechanisms play a central role in the transduction and maintenance of early hormonal and social cues to organize sexually differentiated brain functions.”
“Evidence from neuroimaging studies indicates that depressive symptomatology is associated with inefficient recruitment of prefrontal brain regions while performing tasks that tax executive function.

Methods SSc was induced in BALB/c mice by subcutaneous injections

Methods SSc was induced in BALB/c mice by subcutaneous injections of HOCl daily for 6 weeks. Mice were randomized to treatment with sunitinib, sorafenib, or vehicle. The levels of native and phosphorylated PDGF receptor beta (PDGFR beta) and vascular endothelial growth factor receptor (VEGFR) in the skin were assessed by Western blot and immunohistochemical analyses. Skin and lung fibrosis were evaluated by histologic and biochemical methods. Autoantibodies were detected by enzyme-linked immunosorbent assay, and spleen cell populations were analyzed by flow cytometry. Results Phosphorylation of PDGFR beta

and VEGFR was higher in fibrotic selleck chemical skin from HOCl-injected mice with SSc than from PBS-injected mice. Injections of HOCl induced cutaneous and lung fibrosis, increased the proliferation rate of fibroblasts in areas of fibrotic skin, increased splenic B cell and T cell counts, and increased antiDNA topoisomerase I autoantibody levels in BALB/c mice. All of these features were reduced by sunitinib but not by sorafenib. Sunitinib significantly reduced the phosphorylation

of both PDGF and VEGF receptors. Conclusion Inhibition of the hyperactivated PDGF and selleck products VEGF pathways by sunitinib prevented the development of fibrosis in HOCl-induced murine SSc and may represent a new SSc treatment for testing in clinical trials.”
“Isorhamnetin 3-O-glucoside, which was. contained together with isorhamnetin 3,7-di-O-glucoside in atsumi-kabu leaves, suppressed increases in the plasma ALT and selleckchem AST activities of mice with liver injury induced by the injection of carbon tetrachloride, but no suppression by isorhamnetin 3,7-di-O-glucoside was apparent. This result indicates that the release

of glucose at the 7-position in isorhamnetin 3,7-di-O-glucoside was very important to mitigating liver injury.”
“Imber AN, Putnam RW. Postnatal development and activation of L-type Ca2+ currents in locus ceruleus neurons: implications for a role for Ca2+ in central chemosensitivity. J Appl Physiol 112: 1715-1726, 2012. First published March 8, 2012; doi:10.1152/japplphysiol.01585.2011.-Little is known about the role of Ca2+ in central chemosensitive signaling. We use electrophysiology to examine the chemosensitive responses of tetrodotoxin (TTX)-insensitive oscillations and spikes in neurons of the locus ceruleus (LC), a chemosensitive region involved in respiratory control. We show that both TTX-insensitive spikes and oscillations in LC neurons are sensitive to L-type Ca2+ channel inhibition and are activated by increased CO2/H+. Spikes appear to arise from L-type Ca2+ channels on the soma whereas oscillations arise from L-type Ca2+ channels that are distal to the soma. In HEPES-buffered solution (nominal absence of CO2/HCO3-), acidification does not activate either oscillations or spikes.

Further investigation is warranted Arch Otolaryngol Head Neck Su

Further investigation is warranted. Arch Otolaryngol Head Neck Surg. 2012;138(6):577-583″
“Background: Surgical treatment of stage I non-small cell lung cancer (NSCLC) can be performed either by thoracotomy or by employing video-assisted thoracic surgery (VATS). The aim of this study was to compare long and short-term results of conventional TH-302 datasheet surgery (CS) vs. VATS lobectomy in the treatment of stage I NSCLC. Materials and methods: We performed a retrospective, analytical study of patients undergoing surgery for stage I NSCLC during the period January 1993 to December 2005.

The variables analyzed were overall survival, recurrence, distant metastasis, morbidity, mortality and hospital stay. During this period, 256 anatomic lung resections were performed: 141 by CS and

115 by VATS. Results: There were statistically significant differences in: (i) mean hospital stay in patients with no complications (VATS group: 4.3 days vs. CS group: 8.7 days, P = .0001); (ii) mean hospital stay in patients with complications (VATS: 7.2 days vs. CS: 13.7 days, P =. 0001), and (iii) morbidity (VATS: 15.6% vs. CS: 36.52%, P = .0001). No statistically significant differences were found in: (i) mortality (VATS: 2.17% vs. CS: 1.7%, P = .88); (ii) 5-year overall survival (VATS: 68.1% vs. CS: 63.8%), and (iii) local recurrence and distant metastasis β-Nicotinamide in vitro (P = .82). Conclusions: VATS lobectomy is a safe and effective approach, with a shorter hospital stay and lower morbidity than CS; no statistically significant differences were observed in survival in patients undergoing surgery for stage I NSCLC. (C) 2013 SEPAR. Published by Elsevier Espana, S.L. All rights reserved.”
“Many ecosystem services are public goods whose provision depends on the spatial pattern of land use. The pattern of land use is often determined by the decisions of multiple private landowners. Increasing the provision of ecosystem services, though beneficial for society as a whole, may be costly to private landowners. A regulator interested in providing incentives

to landowners for increased provision of learn more ecosystem services often lacks complete information on landowners’ costs. The combination of spatially dependent benefits and asymmetric cost information means that the optimal provision of ecosystem services cannot be achieved using standard regulatory or payment for ecosystem services approaches. Here we show that an auction that sets payments between landowners and the regulator for the increased value of ecosystem services with conservation provides incentives for landowners to truthfully reveal cost information, and allows the regulator to implement the optimal provision of ecosystem services, even in the case with spatially dependent benefits and asymmetric information.

The association of optimized insulin therapy to “real time contin

The association of optimized insulin therapy to “real time continuous glucose monitoring” allows better doses adaptation. Alarms can be set to avoid glycemic excursions and thus severe hypoglycemia. this website Using these devices, HbA1c is significantly improved without any increase in hypoglycemic events. These devices are one of the steps towards the “closed-loop insulin delivery” concept. Restoration of missing beta-cell function by an automated, glucose-modulated, insulin-delivery system would allow near normal glycemia without the risk of hypoglycemia. First studies show a good regulation of interprandial glycemia; prandial doses seem more difficult to assess. Nevertheless the

“holy grail” might be closer than we think. (C) 2010 Elsevier Masson SAS. All rights reserved.”
“Background and Aim: The progress made in the last few years

have managed to come up withy the possibility of using different stem cell types in an endeavor to correct the alterations that appear in different degenerative diseases. The pancreas, an organ with extremely low regenerative capacity, both for the endocrine and for the exocrine component, is an organ perfect for cell therapy in the hope of restoring its function and cure diabetes mellitus or chronic pancreatitis. One main issue in the stem cell transplantation problem is represented by the influence of the cellular niche, formed by completely differentiated cells, on the phenotype and function of the transplanted cells. In this study, we challenge current knowledge in the

field by evaluating the influence of exocrine selleck compound pancreatic cells on placental stem-like cells using the co-culture technique. Methods: In our experiments, we used two different protocols in which adult pancreatic cells were cultured together with mesenchymal stem cells isolated from human placenta. In the case Small molecule library of the first protocol, we seeded pancreatic cells on a pre-adhered single-cell layer of mesenchymal stem cells and in the second one, the seeding of two cell populations in suspension was done at the same time, after passage. During the experiment, we evaluated the alteration of the morphology of the placental cells using and inverted phase microscope and reverse transcriptase-PCR. Results and Conclusions: Based on morphology, in both cases the interaction between epithelial pancreatic cells and placental ones have determined a change in phenotype from mesenchymal to epithelial-like. Taking into consideration the gene expression, placental stem cells have maintained pluripotency gene expression throughout the study. They also expressed pancreatic amylase. These experiments bring out the plasticity of placental stem cells, the cell microenvironment with a decisive part in phenotype and the level of gene expression. The results obtained in vitro can bring a new picture on the effects of the pancreatic stem cell niche.

01) pre vs post on survey items regarding communication, meeting

01) pre vs. post on survey items regarding communication, meeting with physicians, and obtaining information about their infants. Conclusions: FCR was associated with enhanced collaboration among team members

for NNPs and fellows. Parents’ satisfaction scores increased post FCR on survey items regarding communication. Since NNPs and fellows are the primary communicators with parents, the increased satisfaction may reflect improved communication due to FCR. This added opportunity for open dialogue may also contribute to the increased parent satisfaction.”
“We develop a miniaturized chamber installed on a PLX4032 cell line tandetron accelerator into which negative ions of small carbon clusters are transported. Negative clusters C-1(-)-C-10(-) are obtained with beam currents of 1-10(4) nA at energies of 10-20 keV. C-2(-) beams of 0.2

mu A are used to directly deposit carbon films on SiO2/Si substrates. Formation of ultrathin carbon films are demonstrated by Raman scattering, which reveals the evolution of the graphitic peak (1550 cm(-2)) with deposition time.”
“Here, we describe a new Australian species in journal format and simultaneously open the description in a wild format on the www.species-id.net. The wild format will always link to the fixed original journal description of the taxon, however it permits future edits and additions to species’ taxonomy and biology. The diving beetle Neobidessodes darwiniensis sp. n. (Coleoptera: Dytiscidae, Bidessini) is described based on a single female, Vorinostat collected in a rest pool of the Harriet Creek in the Darwin Area, Northern Territory. Within this website Neobidessodes the new species is well characterized by its elongate oval body with rounded sides, short and stout segments of antennae, length of body and dorsal surface coloration. In addition to external morphology, we used mitochondrial cox1 sequence data to support generic assignment and to delineate the new species from other Australian Bidessini

including all other known Neobidessodes. Illustrations based on digital images are provided here and as online resources. A modified key is provided. Altogether ten species of the genus are now known worldwide, nine from Australia and one from New Guinea.”
“This study examined the longitudinal association between mood episode severity and relationships in youth with bipolar (BP) disorder. Participants were 413 Course and Outcome of Bipolar Youth study youth, aged 12.6 +/- 3.3 years. Monthly ratings of relationships (parents, siblings, and friends) and mood episode severity were assessed by the Adolescent Longitudinal Interval Follow-up Evaluation Psychosocial Functioning Schedule and Psychiatric Rating Scales, on average, every 8.2months over 5.1 years. Correlations examined whether participants with increased episode severity also reported poorer relationships and whether fluctuations in episode severity predicted fluctuations in relationships, and vice versa.

We did not find any significant impact of nutrient addition in an

We did not find any significant impact of nutrient addition in any of the eight short-term (i.e. four days) experiments carried out. Impacts by the snail were minor; we only found a decrease in biomass due to snail grazing in one of the eight experiments, and no impacts on microalgal (i.e. diatom) composition. High ambient nutrient concentrations in the sediment porewater and low snail abundances on the sediment could explain

these findings. Our results suggest that ephemeral, short-term nutrient pulses into eutrophic coastal systems of the Northern Gulf of Mexico, such as Weeks Bay (Alabama, USA), should not greatly affect the abundance of sediment microalgae, even though those pulses occur in well-lit areas. The results further suggest the snail N. reclivata is not a major https://www.selleckchem.com/products/BI-2536.html control of sediment Proteasome inhibitor microalgal populations in the subtidal sedimentary areas studied. Our findings contrast with the results of past work in sediments with well-lit and nutrient poor conditions, or sediments with high densities of other snail grazers. In conjunction this and other investigations

indicate that the response of sediment microalgae to nutrient enrichment and modified grazer abundance depends to a large extent on the initial levels of nutrient availability and grazing before the system is altered. Rev. Biol. Trop. 60 (4): 1687-1706. Epub 2012 December 01.”
“Mitral valve prolapse has a prevalence of 2% to 3% in the general population, with adverse outcomes such as mitral valve regurgitation (MVR), heart failure, and endocarditis. Predictors of outcomes are used in idiopathic mitral valve prolapse for the timing of surgery, but such predictors are unknown in Marfan syndrome. Therefore, a population-based cohort study of 112 patients Compound C (49 male, 63 female; mean age 34 +/- 15 years) with classic Marfan syndrome and mitral valve prolapse with moderate or less MVR at baseline was conducted. During 4.6 +/- 3.6 years of follow-up, progression of MVR was observed in 41 patients and valve-related events, which comprised mitral

valve endocarditis (7 events), heart failure (5 events), and mitral valve surgery (25 events), were observed in 31 patients. Multivariate Cox proportional-hazards regression analysis identified a flail mitral leaflet (hazard ratio [HR] 3.262, 95% confidence interval [CI] 1.406 to 7.566, p = 0.006) and increased indexed end-systolic left ventricular diameters (HR 1.113, 95% CI 1.043 to 1.188, p = 0.001) as independent predictors of progression of MVR. Similarly, mitral valve related events were independently predicted by a flail mitral leaflet (HR 5.343, 95% CI 2.229 to 12.808, p <0.001), and mild (HR 14.336, 95% CI 1.873 to 109.755, p = 0.01) or moderate (HR 16.849, 95% CI 2.205 to 128.76, p = 0.006) degree of MVR. Conversely, aortic dilatation, dural ectasia, and sporadic mode of inheritance were not associated with outcome.

Results: The ICC was 0 86 for the agreement between the HQ an

\n\nResults: The ICC was 0.86 for the agreement between the HQ and the DHI, and 0.77 and 0.85 for the repeatability of the HQ and the DHI, respectively. There were no statistically significant systematic differences in mean intake values between the 2 methods

or between repeated measurements. In subgroup analysis of background variables, there were only minor differences in agreement and repeatability, with somewhat higher ICC values among subjects with a healthier lifestyle and higher education.\n\nConclusions: The high reliability and homogeneity of the health questionnaire make it a useful tool for measuring habitual coffee consumption for NCT-501 the purposes of epidemiological research.”
“Soy protein hydrolysates are used as the most cost effective medium supplement to enhance cell growth and recombinant protein productivity in cell cultures. Such hydrolysates contain diverse classes of compounds,

such as peptides, carbohydrates and phenolic compounds. To identify if specific compounds dominate the functionality of hydrolysates in cell cultures, thirty Tariquidar samples of hydrolysates with different cell culture performances were analyzed for chemical composition using an untargeted metabolomics approach. Out of 410 detected compounds, 157 were annotated. Most of the remaining 253 compounds were identified as peptides, but could not be annotated exactly. All compounds were quantified relatively, based on their average signal intensities. The cell growth and total immunoglobulin (IgG) production, relative to the CD medium (100%), ranged from 148 to 438% and 117 to 283%, respectively. Using bootstrapped stepwise regression (BSR), the NSC-732208 compounds with the highest inclusion frequency were identified. The most important compound, i.e. phenyllactate and ferulate explained 29% and 30% of the variance for cell growth and total IgG production, respectively. Surprisingly, all compounds identified in the BSR showed a positive correlation with cell growth and total IgG production. This knowledge can be applied to monitor the production and accumulation of these compounds during

the production process of hydrolysates. Consequently, the processing conditions can be modulated to produce soy protein hydrolysates with enhanced and consistent cell culture performance. (C) 2013 Elsevier Ltd. All rights reserved.”
“People differ in their susceptibility to developing cancer on exposure to carcinogens such as tobacco. What causes this is largely unknown. One possibility is that it is determined by nutritional influences during development that permanently change the structure and function of the baby’s body. We studied an older and a younger cohort, totaling 20,431 men and women, born in Helsinki during 1924-1933 and 1934-1944. Their body size at birth had been recorded. Of them, 385 had developed lung cancer. Smoking history was known for 6,822 people.

8 months before recurrence Among

the 9 patients treated

8 months before recurrence. Among

the 9 patients treated with bevacizumab (including 5 patients who had transpupillary thermotherapy as a primary treatment), 5 showed resolution of serous macular detachment and the median logMAR BCVA improved from 0.7 to 0.5 (P = .042). Among these 5 patients, 3 had sustained resolution for a mean duration of 5.7 months Quisinostat ic50 and 2 showed recurrent serous macular detachment after 3 and 12 months.\n\nCONCLUSION: Transpupillary thermotherapy and intravitreal bevacizumab appear effective in the management of symptomatic circumscribed choroidal hemangioma, although recurrence of serous macular detachment and CME developed after long-term follow-up of transpupillary thermotherapy, and the duration of treatment effectiveness appears to be short with bevacizumab. (Am J Ophthalmol 2012;154:137-145. (C) 2012 by Elsevier Inc. All rights reserved.)”
“Tomasi M, Canato M, Paolini C, Dainese M, Reggiani C, Volpe P, Protasi F, Nori A. Calsequestrin (CASQ1) rescues function and structure of calcium release units in skeletal muscles of CASQ1-null mice. Am J Physiol Cell Physiol

302: C575-C586, 2012. First published November 2, 2011; doi: 10.1152/ajpcell.00119.2011.-Amplitude of Ca2+ transients, ultrastructure of Ca2+ release units, and molecular composition of sarcoplasmic reticulum (SR) are altered in fast-twitch skeletal muscles of calsequestrin-1 (CASQ1)-null mice. To determine whether such changes are directly

caused by CASQ1 MDV3100 order ablation or are instead the result of adaptive mechanisms, here we assessed ability of CASQ1 in rescuing the null phenotype. In vivo reintroduction of CASQ1 was carried out by cDNA electro transfer selleck compound in flexor digitorum brevis muscle of the mouse. Exogenous CASQ1 was found to be correctly targeted to the junctional SR (jSR), as judged by immunofluorescence and confocal microscopy; terminal cisternae (TC) lumen was filled with electron dense material and its width was significantly increased, as judged by electron microscopy; peak amplitude of Ca2+ transients was significantly increased compared with null muscle fibers transfected only with green fluorescent protein (control); and finally, transfected fibers were able to sustain cytosolic Ca2+ concentration during prolonged tetanic stimulation. Only the expression of TC proteins, such as calsequestrin 2, sarcalumenin, and triadin, was not rescued as judged by Western blot. Thus our results support the view that CASQ1 plays a key role in both Ca2+ homeostasis and TC structure.”
“Parkinson’s disease (PD) is a neurodegenerative disorder characterized by a preferential loss of dopaminergic (DAergic) neurons of the substantia nigra pars compacta (SNpc).

We performed a standardized clinical evaluation that included cal

We performed a standardized clinical evaluation that included calculation of the revised cardiac risk index (rCRI) and measurement of the AAI using both palpation and Doppler techniques. Independent observers, blinded to preoperative assessment and AAI results, ascertained cardiac complications in the first 7 days after surgery. We assessed the ability of an abnormal AAI (<= 0.9 or absence of all four pedal pulses) to predict postoperative cardiac complications using likelihood ratios (LR), area under the ROC curves (AUC), and multivariable logistic regression in which we adjusted for the rCRI result.\n\nRESULTS: eFT-508 The cohort had a median age of 67 yr, 60% were male, 19% had diabetes,

14% had ischemic heart disease, and 35% underwent intraperitoneal or intrathoracic surgery. Postoperatively, 14 of 242 (6%) patients suffered cardiac complications, but no patients died. An abnormal AAI was present in 44 patients, 10 (23%) of whom had postoperative cardiac complications: positive LR 4.79 (95% Cl: 3.04-7.54), negative LR 0.34 (95% CI: 0.15-0.77),

AUC = 0.80. The AAI compared favorably with the rCRI, which had positive LR this website 4.22 (95% CI: 2.24-7.95), negative LR 0.57 (95% CI: 0.34-0.96), and AUC = 0.74. In multivariate analysis, the adjusted odds ratio for having a cardiac complication was 10.16 (95% CI: 2.90-36.02) for those patients with an abnormal AAI, even after adjusting for rCRI results.\n\nCONCLUSIONS: An abnormally low AAI, indicative of underlying peripheral arterial disease, is an independent risk factor for postoperative cardiac complications. The accuracy of the AAI is similar to the rCRI, and it provides additional

independent predictive value for preoperative cardiac risk stratification.”
“The maxi-anion channel has been observed in many cell types from the very beginning of the patch-clamp era. The channel is highly conductive for chloride and thus can modulate the resting membrane potential and play a role in fluid secretion/absorption and cell volume regulation. A wide nanoscopic pore of the maxi-anion channel permits passage of excitatory amino acids and nucleotides. The channel-mediated release of these NVP-LDE225 inhibitor signaling molecules is associated with kidney tubuloglomerular feedback, cardiac ischemia/hypoxia, as well as brain ischemia/hypoxia and excitotoxic neurodegeneration. Despite the ubiquitous expression and physiological/pathophysiological significance, the molecular identity of the maxi-anion channel is still obscure. VDAC is primarily a mitochondrial protein: however several groups detected it on the cellular surface. VDAC in lipid bilayers reproduced the most important biophysical properties of the maxi-anion channel, such as a wide nano-sized pore, closure in response to moderately high voltages, ATP-block and ATP-permeability.