Of them, 54 patients were classified as

H0 (primary disc degeneration Selleckchem VS-6063 without previous surgery), 98 as H1 (disc degeneration with associated herniation without previous surgery), 36 as H2 (disc degeneration with recurrence of disc herniation with previous surgery), and 33 as H3 (postdiscectomy syndrome with previous surgery). Clinical evaluation was based on Oswestry Disability Index and lumbar and radicular visual analogic scale. Each measurement was performed preoperatively, and at 3, 6, 12, and 24 months postoperatively.

Results. Mean follow-up of the series was 30 months (24-72 months). A significant (P < 0.05) clinical improvement was found between preoperative and the last follow-up evaluation for each group. On a multivariate analysis between different groups, a significantly higher Oswestry Disability Index was found in the group classified Tariquidar as H3 (postdiscectomy syndrome) at the final follow-up. The size

of the effect was measured at +0.44 (0.19; 0.69).

Conclusion. Total lumbar disc arthroplasty provides a significant clinical improvement for patients with disc degenerative disease, with a 2-year minimal follow-up. The poorest results were found in patients with previous surgical procedure on the concerned level (postdiscectomy syndrome). These results can be helpful for selection of total disc arthroplasty indications and for the information that a surgeon must give to his or her own patient on the expected result after disc replacement.”
“The flavin monooxygenases (FMO) encoded by plant YUCCA

genes are thought to catalyze a rate-limiting step in the tryptamine pathway for indole-3-acetic acid biosynthesis. Recent experiments with different plant models have indicate that YUCCA genes play essential roles in growth and development through their contribution to the local pool of free auxin. In this study we have characterized five new genes that encode YUCCA-like FMOs in the tomato genome (ToFZY2 to ToFZY6), including gene structure, conserved motifs and phylogenetic analyses. As a first step towards clarifying the individual functions of ToFZY genes, we have used quantitative real-time RT-PCR to conduct a systematic comparison of the steady-state mRNA levels of 6 ToFZY genes, in 33 samples representing major organs and the entire find more tomato life cycle. We followed an absolute quantification strategy which allowed us to cross-compare transcript levels among different ToFZY genes in a given spatiotemporal coordinate. Our results indicate that expression of ToFZY genes is temporally and spatially regulated, and that the distinctive expression pattern of each ToFZY gene partially overlaps with other members of the multigenic family. We compare our data with previous results in other plant species and make some predictions about the role of tryptamine pathway in tomato growth and development. (C) 2011 Elsevier Masson SAS. All rights reserved.

05). Trainees, however, varied significantly in their use of access sheath (P = 0.03). Trainees, male sex, balloon dilation, ureteral access sheath, and residual stones maintained

their significance as predictors of FT on multivariate analysis.

Conclusion: PGTs, in addition to male sex, balloon dilation, ureteral access sheath, and residual stones were significant predictors of FT during URS. Whether these differences in the behavior of PGTs are intrinsic to themselves or from perioperative factors remains to be clarified.”
“Supercritical fluid chromatography (SFC) has developed rapidly in recent years, particularly in the area of enantioseparations. The merits of SFC (e.g., fast analysis speed, wide polarity mTOR inhibitor compatibility, lower cost of the mobile phase and higher column efficiency) would in many cases make it a better choice than high-performance liquid chromatography in drug discovery for the pharmaceutical industry.

Packed-column Bioactive Compound Library SFC meets the gradual rise in demand for simultaneous chiral and achiral separations, impurity quantitation and direct scaling up from the pharmaceutical purifications achieved in the laboratory, especially for chiral drugs.

This review focuses mainly on the latest examples of pharmaceutical separations with chiral stationary phases in SFC for efficient analyses and preparative-scale purifications. (c) 2012 Elsevier Ltd. All rights reserved.”
“The Infectious Disease

Surveillance Center, National Institute of Infectious Diseases, Japan, has developed

a fully automatic system for daily reporting of ILI (influenza-like illness) patients prescribed Oseltamivir and Zanamivir. The system collected data on the number of prescriptions from approximately 3350 pharmacies, which account for almost 7% of all pharmacies in Japan, and published the number online on a daily basis, except for Sundays. On the basis of these data, we further estimated R (v) and predicted its course every Monday using a very simple SIR model with data from previous studies. This paper summarizes our real-time estimation and prediction of ILI patients in the 2009 influenza GSK1120212 cell line A/H1N1 pandemic. The estimate on November 29 resulted in an R (v) of 1.72 (95%CI [1.69, 1.75]). The model predicted that the peak of the epidemic would be reached on December 23 2009 [December 14, 2009, January 2, 2010] with an estimated number of ILI patients of 227,000 [193,000, 262,000]. The cumulative number of ILI patients over the period would be as high as 17.8% [16.6, 19.0%] of the total population of Japan. This information was circulated weekly among central and local government officers in charge of pandemic control to provide updates on the pandemic situation and to aid their decision-making on control strategies. In conclusion, for the first time in the world, we successfully demonstrated real-time estimation and prediction for the entire course of a pandemic, and which could be used routinely for planning counter-measures.

The 810-nm diode laser showed the following results: after 60 s of irradiation with 2 W of continuous mode the temperature gradient in the cervical area of the implant (a dagger Tc) was 37.2A degrees C, while in the apical area (a dagger Ta) was 27.2A degrees C. The 980-nm diode laser showed the following results: after 60 s of irradiation with 2 W continuous mode a dagger Tc was 41.1A degrees C, and a dagger Ta was 30.6A degrees C. The 810-nm diode laser with 2 W continuous mode generated a temperature increase BIX-01294 of

10A degrees C after only 14 s. The 980-nm diode lasers groups produced a much more rapid temperature increase. In only 12 s, the continuous wave of 980 nm reached the 10A degrees C temperature rise. From the present in vitro study it was concluded that the irradiation of implant surfaces with diode lasers may produce a temperature increase above the critical threshold (10A degrees C ) after only 10 s.”
“Acute kidney injury (AKI)

may result from ischemia or by the use of nephrotoxic agents. The incidence of AKI is variable, depends on comorbidities, and ranges from 5 to 35% in all hospitalized patients. The mechanisms of kidney injury exist within a large network of signaling pathways driven by interplay of inflammatory cytokines/chemokines, VX-680 clinical trial reactive oxygen species (ROS), and apoptotic factors. The effects and progression of injury overlap extensively with the remarkable ability of the kidney to repair itself both by intrinsic and extrinsic mechanisms that involve specific cell receptors/ligands as well as possible paracrine influences. The fact that kidney injury is usually part of a generalized

comorbid condition makes it all the more challenging in terms of assessment Selleckchem Proteasome inhibitor of severity. In this review, we attempt to analyze the mechanisms of ischemic injury and repair in acute and chronic kidney disease from the perspectives of both preclinical and human studies. (C) 2011 John Wiley & Sons, Inc. WIREs Syst Biol Med 2011 3 606-618 DOI: 10.1002/wsbm.133″
“To assess and monitor the common event of neurosensory disturbance to the inferior alveolar nerve (IAN) after bilateral sagittal split osteotomy, we used clinical sensory tests and neurophysiologic test sensory action potentials. The diagnostic value of these tests was evaluated by comparing them with the degree of nerve damage reported by patients. Fourteen patients undergoing bilateral sagittal split osteotomy were analyzed preoperatively and 2 years postoperatively. Patients were evaluated bilaterally for positive and negative symptoms: light touch sensation, paraesthesia, hyperesthesia, and dysaesthesia; a “”sensation score” was then calculated for each patient.

Recently we have demonstrated its important role in determining the susceptibility of cells or tissues to diabetes-induced oxidative

stress and/or damage. Therefore, this review will specifically summarize the information available regarding the effect of Nrf2 on the diabetic complications with a focus on diabetic cardiomyopathy and nephropathy. Given the feature that Nrf2 is easily induced by several compounds, we also discussed the role of different Nrf2 activators in the prevention or therapy of various diabetic complications. These findings suggest that Nrf2 has a potential application in the clinic setting for diabetic patients in the short future.”
“Background: A wide range of possible malaria vaccines is being considered and there is a need to identify which vaccines should be prioritized for clinical AZD4547 cost development. An important element of the information needed for this prioritization is a prediction of the cost-effectiveness of potential vaccines in the transmission settings in which they are likely to be deployed. This analysis needs to consider a range of delivery modalities to ensure that clinical development plans can be aligned with the most appropriate deployment strategies.

Methods: The simulations are based on a previously published individual-based stochastic model Vactosertib inhibitor for the natural history and epidemiology of Plasmodium falciparum

malaria. Three different vaccine types: preerythrocytic vaccines (PEV), blood stage vaccines (BSV), mosquito-stage transmission-blocking vaccines (MSTBV), and combinations of these,

are considered each delivered via a range of delivery modalities (Expanded Programme of Immunization – EPI-, EPI with booster, and mass vaccination combined with EPI). The cost-effectiveness ratios presented are calculated for four health outcomes, for assumed vaccine prices of US$ 2 or US$ 10 per dose, projected over a 10-year period.

Results: The simulations suggest that PEV will be more cost-effective in low transmission settings, while BSV at higher transmission settings. Combinations of BSV and PEV are more efficient than PEV, especially in moderate to high transmission settings, while compared to BSV they are BLZ945 more cost-effective in moderate to low transmission settings. Combinations of MSTBV and PEV or PEV and BSV improve the effectiveness and the cost-effectiveness compared to PEV and BSV alone only when applied with EPI and mass vaccinations. Adding booster doses to the EPI is unlikely to be a cost-effective alternative to delivering vaccines via the EPI for any vaccine, while mass vaccination improves effectiveness, especially in low transmission settings, and is often a more efficient alternative to the EPI. However, the costs of increasing the coverage of mass vaccination over 50% often exceed the benefits.

Yet the most GC rich genes in these organisms do show such a signal. We conclude that reduced stability of the mRNA secondary structure near the start codon is a universal feature of all cellular life. We suggest that the origin of this reduction is selection for efficient recognition of the start Caspase activity assay codon by initiator-tRNA.”
“Correlative analysis of molecular markers with phenotypic signatures is the simplest model for hypothesis generation. In this paper, a panel of 24 breast cell lines was grown in 3D culture, their morphology was imaged through phase contrast microscopy, and computational methods were developed to segment and represent each colony at multiple dimensions. Subsequently, subpopulations from these

morphological responses were identified through consensus clustering to reveal three clusters of

round, grape-like, and stellate phenotypes. In some cases, cell lines with particular pathobiological phenotypes clustered together (e.g., ERBB2 amplified cell lines sharing the same morphometric properties as the grape-like phenotype). Next, associations with molecular features were realized through (i) differential analysis within each morphological cluster, and (ii) regression analysis across the entire panel of cell lines. In both cases, the dominant genes that are predictive of the morphological signatures were identified. Specifically, PPAR gamma has been associated with the invasive stellate morphological phenotype, which corresponds to triple-negative pathobiology. PPAR gamma has been validated through two supporting biological assays.”
“Alzheimer’s BX-795 purchase disease www.selleckchem.com/products/acy-738.html (AD) is a neurodegenerative disease with major clinical hallmarks of memory loss, dementia, and cognitive impairment. Neuroinflammation is involved in the onset of several neurodegenerative disorders. Astrocyte is the most abundant type of glial cells in the central nervous system (CNS) and appears to be involved in the induction of neuroinflammation. Under stress and injury, astrocytes become astrogliotic leading to an upregulation of the expression

of proinflammatory cytokines and chemokines, which are associated with the pathogenesis of AD. Cytokines and related molecules play roles in both neuroprotection and neurodegeneration in the CNS. During early AD pathogenesis, amyloid beta (A beta), S100B and IL-1 beta could bring about a vicious cycle of A beta generation between astrocytes and neurons leading to chronic, sustained and progressive neuroinflammation. In advanced stages of AD, TRAIL secreted from astrocytes have been shown to bind to death receptor 5 (DR5) on neurons to trigger apoptosis in a caspase-8-dependent manner. Furthermore, astrocytes could be reactivated by TGF beta 1 to generate more A beta and to undergo the aggravating astrogliosis. TGF beta 2 was also observed to cooperate with A beta to cause neuronal demise by destroying the stability of lysosomes in neurons.

(c) 2009 Elsevier Ltd. All rights reserved.”
“Recent genome-wide single nucleotide polymorphism (SNP) association studies (GWAS) have identified a number of SNPs that were significantly associated with coronary artery disease (CAD) and myocardial infarction (MI). We tested for replication of the previously described association with CAD in our case-control datasets of SNPs variants located at 1p13.1, 2q33.1, 10q11.1,

9p21, and 21q22. We observed a small significant risk associated of the SNP rs10757274 with CAD in the PROCAGENE study. Besides, the multilocus combination rs10757274 and rs1333048 gave a near significant result. We confirmed that the SNP rs10757274 www.selleckchem.com/products/jq-ez-05-jqez5.html showed association with CAD in the PROCAGENE study,

although after applying the Bonferroni S63845 order correction was not longer significant. Independent replication studies in other populations are needed to unequivocally confirm the association.”
“Fractal development during polymerization of a dimethacrylate system (Bis-GMA/TEGDMA) has been studied through the analysis of time series obtained sequentially by pulsed photoacoustics. The photoacoustic signals as obtained in situ during photopolymerization of Bis-CMA/TEDGMA were analyzed by rescaled range analysis, dispersion analysis, and detrended fluctuation analysis methods. The analysis reveals the presence of more than one scaling parameter and, therefore, belongs to a complex process known as multifractal. The evolution of fractality during photopolymerization was compared under equivalent conditions p38 inhibitors clinical trials with the chemical conversion (of dimethacrylate double bonds) as a function of time, as monitor by infrared spectroscopy. This kinetic Study was also used to correlate the fractal nature of the dimethacrylate reaction system with the condensed-state transitions emerging during the photochemical reaction. (c) 2008 Wiley Periodicals, Inc. J Appl Polym Sci 111: 1199-1208, 2009.”
“OBJECTIVE: To systematically review Indian literature

on delays in tuberculosis (TB) diagnosis and treatment.

METHODS: We searched multiple sources for studies on delays in patients with pulmonary TB and those with chest symptoms. Studies were included if numeric data on any delay were reported. Patient delay was defined as the interval between onset of symptoms and the patient’s first contact with a health care provider. Diagnostic delay was defined as the interval between the first consultation with a health care provider and diagnosis. Treatment delay was defined as the interval between diagnosis and initiation of anti-tuberculosis treatment. Total delay was defined as time interval from the onset of symptoms until treatment initiation.

RESULTS: Among 541 potential citations identified, 23 studies met the inclusion criteria. Included studies used a variety of definitions for onset of symptoms and delays.

4 vs 1.6% and 19.4 vs 8.8%, respectively). The cancer disease promoted the development of dysthymia (n = 4 new cases/6 two-year prevalent cases) and PTSD (7/7) and the re-emergence of MDD (n NSC 66389 = 21 relapses/28 three-year prevalent cases) and GAD (10115). No improvement in serious mood disorders such as MDD (16.0 vs 7.2%) and dysthymia (4.2 vs 0%) was reported at the time of interview, more than 1.75 years (median time) after the cancer surgery, the prevalence being 2-4 times greater in breast cancer survivors than in controls.

Conclusion: Despite significant advances in treatment, a diagnosis of breast cancer is highly associated with various forms of psychopathology, regardless

of psychiatric history, with symptoms persisting after treatment.

These results may assist clinicians in planning mental healthcare for women with breast cancer. Copyright (C) 2009 John Wiley & Sons, Ltd.”
“Rheumatoid arthritis (RA) is a systemic, inflammatory, autoimmune disorder with progressive articular damage that may result in lifelong disability. Although major strides in understanding the disease have been made, the pathogenesis of RA has not yet been fully elucidated. Early treatment can prevent severe disability and lead to remarkable patient benefits, although a lack of therapeutic efficiency in a considerable number of patients remains problematic.

MicroRNAs (miRNAs) are small, non-coding RNAs that, depending CAL-101 molecular weight upon base pairing to messenger RNA (mRNA), mediate mRNA cleavage, translational repression or m RNA destabilization. As fine tuning regulators of gene expression, miRNAs are involved in crucial cellular processes and their dysregulation has been described in many cell types in different diseases. In body fluids, miRNAs are present in microvesicles or

incorporated into complexes with Argonaute 2 (Ago2) or high-density lipoproteins and show high stability. Therefore, they are of interest as potential biomarkers of disease in daily diagnostic applications. Targeting miRNAs by gain or loss of function approaches have brought therapeutic effects in various animal models.

Over the past several years it has become clear that alterations exist in the expression of miRNAs in patients with RA. Increasing numbers of studies VX-680 concentration have shown that dysregulation of miRNAs in peripheral blood mononuclear cells or isolated T lymphocytes, in synovial tissue and synovial fibroblasts that are considered key effector cells in joint destruction, contributes to inflammation, degradation of extracellular matrix and invasive behaviour of resident cells. Thereby, miRNAs maintain the pathophysiological process typical of RA.

The aim of the current review is to discuss the available evidence linking the expression of miRNAs to inflammatory and immune response in RA and their potential as biomarkers and the novel targets for treatment in patients with RA.

7). Compared with participants who typically ate no fish, those with a high fish intake had a similar dementia risk (hazard ratio: 0.95; 95% CI: 0.76, 1.19), as did those who typically ate fatty fish (hazard ratio: 0.98; 95% CI: 0.77, 1.24). Dietary intakes of APR-246 omega-3 PUFAs were also not associated with dementia risk, and the results were similar when we considered AD specifically.

Conclusion:

In this Dutch cohort, who had a moderate consumption of fish and omega-3 PUFAs, these dietary factors do not appear to be associated with long-term dementia risk. Am J Clin Nutr 2009;90:170-6.”
“Two siblings presented with encephalopathy, lactic acidosis, and hypocitrullinemia. Muscle this website and liver biopsies were considered for respiratory chain studies, but because of hypocitrullinemia, molecular analysis for maternally inherited Leigh syndrome was first performed, revealing in both siblings the mitochondrial

DNA T8993G mutation (95% heteroplasmy), allowing to avoid tissue biopsies. Hypocitrullinemia, an occasional finding in mitochondrial diseases, has been specifically associated with T8993G mutation. However, only few patients have been reported, and the prevalence of hypocitrullinemia in 8993 mitochondrial DNA mutations is unknown. In a small series of 16 Leigh syndrome patients, sensitivity and specificity of hypocitrullinemia (<= 12 mu mol/L) for 8993 mitochondrial DNA mutations were 66% and 85%, respectively. Although studies in larger cohorts are necessary, we suggest considering T8993G mutation early in the diagnostic evaluation of infantile mitochondrial diseases with hypocitrullinemia, which minimizes the need for invasive procedures associated with a small but nonnegligible risk of complications and incorrect diagnosis.”
“Although continuity of care (CoC) is a cornerstone of many health policies, there is no theoretically driven model of CoC that incorporates the experiences of older adults. We evaluated such a model in data collected for another purpose.

We used data on 2,620 Medicare beneficiaries who completed all of the necessary components of the 2004

National Health and Health Services Use Questionnaire (NHHSUQ). The NHHSUQ solicited https://www.selleckchem.com/products/pf-04929113.html information on usual primary provider, place of care, and the quality and duration of the patient-provider relationship. We used confirmatory factor analysis to evaluate the patient-reported CoC model and examined factorial invariance across sex, race/ethnicity, Medicare plan type, and perceived health status.

Our thirteen-item CoC model consisted of longitudinal (care site and provider duration) and interpersonal (instrumental and affective) domains. Although the overall chi-square goodness-of-fit statistic was significant (chi (2) = 1,091.8, df = 57, p < .001), model fit was good based on standard indices (GFI = 0.94, NFI = 0.96, CFI = 0.96, RMSEA = 0.08).

CdS/Si-NPA was obtained

by depositing a continuous film of CdS onto silicon nanoporous pillar array (Si-NPA) via a chemical bath deposition (CBD) method and the average reflectance of CdS/Si-NPA was less than 7% in the wavelength range of 200-1000 nm. Under 1 sun air mass (AM) 1.5 G illumination, CdS/Si-NPA exhibits an obvious photovoltaic effect. These results indicate that CdS/Si-NPA has a strong broadband optical antireflection and might be a promising candidate for the assembly of high efficiency solar cells. (C) 2011 American Institute of Physics. [doi:10.1063/1.3658814]“
“A 64-yr-old man with end-stage kidney disease caused by hypertensive nephrosclerosis underwent living-unrelated ABO-identical kidney transplantation (KTx) at the age of 60 yr from his 60-yr-old wife. Maintenance trough concentration Selleck Alvocidib of cyclosporine A (CsA) was 100 +/- 30 ng/mL. Five months after KTx, proteinuria gradually increased to around Pevonedistat 1 g/d. TRBx at eight months after KTx revealed the new-onset alteration of mild arteriolosclerosis with intimal hyalinosis, which might reflect calcineurin inhibitor (CNI)associated arteriopathy (CAA). Nearly one and half years after KTx, urinary protein excretion

became nearly 2 g/d. TRBx revealed the advanced CAA and findings of focal segmental glomerulosclerosis (FSGS). Then, CNI was switched from CsA to tacrolimus (TAC). TRBx at two and half years after KTx revealed progressed arteriolar transmural thickening and striped fibrosis, which were supposed to be induced by an increase in

serum TAC concentration because of acute enterocolitis. Then, TAC dose was reduced to serum trough concentration 58 ng/mL, but urinary protein excretion was increased up to 10 g/d. Reduction of TAC to trough concentration 2.0 +/- 0.5 ng/mL reduced urinary protein excretion. Attempts to elevate TAC trough concentration within normal range (48 ng/mL) reproducibly induced the recurrence of an increase in sCr or urinary protein excretion. All these findings supported the etiology of Nirogacestat graft dysfunction, and proteinuria of this case was FSGS.”
“The aim of this study was to determine if a meloxicam hydrogel could be administered in vivo via phonophoretic transdermal delivery using pulsed ultrasound by examining its anti-hyperalgesic effects in a rat carrageenan inflammation model. Carrageenan (1%) was injected into the plantar surface of the right hindpaw, and meloxicam hydrogel was administered via phonophoretic transdermal delivery. Changes in the mechanical and thermal hyperalgesia, as well as swelling, showed that phonophoretic delivery of meloxicam exhibited significantly better anti-hyperalgesic and anti-inflammatory effects than pulsed ultrasound. Topical and systemic application of meloxicam hydrogel using phonophoresis showed similar anti-hyperalgesic effects.

Objective. To investigate the course of back pain (BP) across 5 years and the impact of BP history on its incidence and recurrence.

Summary of Background Data. Longitudinal studies on BP performed in the general population have reported varying prevalence and incidence rates. Most studies compared two points in time with varying time periods. This study adds information about the course of BP exploring five ZIETDFMK points in time with annual intervals.

Methods. The Swiss Household Panel is a representative population-based cohort study (N = 7799). The question analyzed in the present study

asked about “”bad back or lower back problems at least once a month in the last 12 months (BP).”" Among 7791 persons who answered this question during the baseline survey in 1999, 3881 persons (49.8%) completed all annual follow-up surveys through 2003 and represent the study sample. In each year, the 1-year prevalence, incidence, and recurrence of BP were calculated. The course of BP was analyzed according to the number of years with BP, the constancy of BP Wnt inhibitor review status, and the trend of BP. For each analysis, the observed frequency was compared with expected frequencies on the basis of two theoretical models.

Results. In the study sample (age 44.0 +/- 15.6 years, 57.7% women), BP prevalence was 33.2% at

baseline. In the follow-up surveys, mean prevalence was 37.7%, mean incidence 19.6%, and mean recurrence 69.0%. The most frequently observed courses across 5 years were those with a constant status: BP always absent (n = 1346, 34.7%) or BP always present (n = 538, 13.9%). BP recurrences increased with increasing numbers of previous consecutive years with BP from

46.9% (1 year of previous BP) to 88.1% (at least 4 years of previous BP).

Conclusion. BP history is highly predictive for future BP episodes.”
“De novo thrombotic microangiopathy(TMA) is most commonly triggered by calcineurin inhibitors (CNI) and the prognosis is less severe than with recurrent TMA. However, it is difficult to distinguish de novo TMA from CNI toxicity and acute antibody-mediated rejection(AMR) soon after renal transplantation. We present a case of tacrolimus-associated TMA soon after Ulixertinib molecular weight ABO blood type incompatible renal transplantation that was difficult to differentiate from acute AMR. On day 9 his urine output decreased dramatically and the Scr level increased. His anti-blood type A antibody titer increased to x16 postopratively and the tacrolimus trough level was higher than in our immunosuppressive regimen. Although we gave priority to anti-AMR treatment, adequate dose adjustment of tacrolimus after tacrolimus nephrotoxicity was diagnosed from graft biopsy could correct allograft dysfunction.”
“Study Design. Analysis of Nationwide Inpatient Sample (NIS) database for data related to spinal fusion procedures.

Objective.