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PubMed1989

Nicardipine and propranolol in the treatment of essential hypertension.

Two hundred thirty-four patients with supine diastolic blood pressure of between 95 and 114 mm Hg were enrolled into a double-blind, randomized, parallel, multicenter trial. The patients were randomized to either nicardipine 30 mg tid, propranolol 40 mg tid, or nicardipine 30 mg tid and propranolol 40 mg tid for six weeks. Two hundred six patients yielded data for analyses. Of the 28 not included, seven had missing data, whereas the remaining 21 were excluded because they either failed to meet inclusion criteria or were noncompliant at endpoint. Both nicardipine and propranolol as monotherapies and in combination achieved statistically significant, (P less than .01), supine diastolic blood pressure reduction relative to baseline. The combination of nicardipine and propranolol showed a greater reduction in supine diastolic and systolic measurements than either of the monotherapies. Nicardipine produced greater blood pressure reductions one hour after dosing, whereas the propranolol treatment tended to produce slightly greater blood pressure decreases eight hours after dose. The combination always resulted in the greatest blood pressure reduction, independent of time after dose. Adverse experiences were reported by 26% of patients in the nicardipine-treated group, most often transient vasodilatory effects, by 17% of the propranolol-treated patients, and by 18% of the combination-treated group. This study demonstrated at the doses studied that nicardipine alone produced equivalent blood pressure reductions to those obtained by propranolol alone, but that the combination of these two drugs produced greater reductions in blood pressures than either of the monotherapies.

Adult↗
PubMed2004

Haplotypic analyses of the IGF2-INS-TH gene cluster in relation to cardiovascular risk traits.

The IGF2-INS-TH genomic region has been implicated in various common disorders including the metabolic syndrome, type 2 diabetes and coronary heart disease (CHD). Here we present detailed haplotype analysis of 2743 males 51-62 years old in relation to body weight and composition, blood pressure (BP) and plasma triglycerides (TG). Use of the total data set was complicated by the number of loci typed, missing data, multi-allelic markers and continuous trait phenotypes. Different algorithms and subsets of the data were analysed using the programmes haplotype trend regression, haplo.score, evolutionary-based haplotype analysis package and Phase, in conjunction with SPSS. Ten haplotypes designated in frequency order *1(20.0%) to *10(3.4%) represented 89% of all haplotypes. Haplotype *5 protected against obesity. Haplotype *4 carriers exhibited elevated BP and fat mass, haplotype *6 was associated with raised plasma TG levels. Haplotype *8 also showed similar magnitude effects as *4. These cohort trait analyses and detailed haplotypic analyses enable integration with published case data. Haplotypes *4, *6 and *8 are the only INS VNTR class III-bearing haplotypes, although differing in flanking haplotype, whereas *5 displays unique features in all three genes (with significant commonality with type 1 diabetes-predisposition haplotypes). We propose that long repeat insertion in the insulin gene promoter ('class III'), reported to result in low insulin production, predisposes to the metabolic syndrome features of elevated BP, fat mass or TG level, therefore appearing more frequently in type 2 diabetic, polycystic ovary syndrome and CHD cases. The functional element(s) of *5 for weight-lowering could reside in any of the three genes.

Aged↗
PubMed1998

Molecular phylogeny of the genus Hypochaeris using internal transcribed spacers of nuclear rDNA: inference for chromosomal evolution.

Sequences of the internal transcribed spacers (ITSs) of 18S-26S nuclear ribosomal DNA were used to resolve phylogenetic relationships and chromosomal evolution among 14 species of the genus Hypochaeris (Asteraceae). Parsimony analysis was performed for phylogenetic reconstruction, and sequence divergence between species was estimated. Pairwise sequence divergence within Hypochaeris genus ranged from 0% to 25.68% in ITS1 and from 0% to 17.08% in ITS2. A highly resolved strict-consensus tree was obtained that showed the phylogenetically useful information of ITS sequences within the genus Hypochaeris. Four clades could be well distinguished, one of them formed by the single species H. robertia, which appeared to be the most related to the ancestral species of the genus. The results agree with taxonomic classification based on morphological data, and the tree obtained, when indels are coded as missing data, aggregates the species having the same chromosome number, except in one clade. According to the ITS phylogenetic tree, the chromosomal evolution within the genus Hypochaeris conflicts with the previous hypothesis and suggests that karyotype evolution in Hypochaeris was accompanied with both decreasing and increasing dysploidy, probably with several chromosomal rearrangements, and from an ancestral basic chromosome number of 4 or 5.

Asteraceae↗
PubMed1995

The feasibility and cost of a large multicentre audit of process and outcome of prostatectomy.

Objective--To determine the feasibility of performing multicentre process and outcome audits of common interventions taking prostatic procedures as an example. Design--Prospective, cohort study. Setting--All National Health Service and independent hospitals in Northern, Wessex, Mersey, and South West Thames health regions. Patients--5361 men undergoing prostatectomy identified by 103 of the 107 urologists and general surgeons performing prostatectomy in the study regions. Main measures-- Rates of participation by surgeons and patients; completeness of clinical data provided by surgeons; patient response rate and completeness of patient derived data; and cost. Results--Most surgeons (103,96%) agreed to participate. Overall, the proportion of eligible patients invited to take part was high (89%), although this was only measured in South West Thames, where dedicated data collectors were employed. Few men (80, 1.5%) declined to participate. Of those surviving for three months after surgery, 82.4% (4226) completed and returned the postal questionnaire. The response rate was higher in South West Thames (86.7%) than in the other regions (80.6%-80.8%). The audit was well received: 91% of patients found the questionnaire easy to complete and only 2.3% of them disapproved. Completeness of data was high with both the hospital and patient questionnaires. Missing data occurred in less than 5% of responses to most questions. The attributable cost was 34.50 pounds per patient identified or 44 pounds for patients in whom either the treatment outcome or vital status was known three months after their prostatectomy. Conclusions--This multicentre audit of process and outcome of prostatectomy proved feasible in terms of surgeon participation, patient identification, and the quantity and quality of data collection. Whether the cost was warranted will depend on how surgeons use the audit data to modify their practice.

Aged↗
PubMed2006

Pharmacotherapy for post-traumatic stress disorder - a systematic review and meta-analysis.

BACKGROUND: Post-traumatic stress disorder (PTSD) is a prevalent and disabling condition. Evidence that PTSD is characterized by specific psychobiological dysfunctions has contributed to a growing interest in use of medication in its treatment. OBJECTIVES: To assess the effects of medication in the treatment of PTSD. DESIGN: Systematic review of randomised controlled trials (RCTs) following the Cochrane Collaboration guidelines. A more detailed version of the review is published in the Cochrane Database of Systematic Reviews. METHODS: We searched the Cochrane Depression, Anxiety and Neurosis Group specialised register, the Cochrane Central Register of Controlled Trials (Cochrane Library issue 4, 2004), MEDLINE (January 1966 - December 2004), PsycINFO (1966 - 2004), the National PTSD Center Pilots database, and the meta register module of the Controlled Trials database. Reference lists of retrieved articles were searched for additional studies. Two raters independently assessed RCTs for inclusion in the review, collated trial data, and assessed trial quality. Investigators were contacted to obtain missing data. Summary statistics were stratified by medication class, and by medication agent for the selective serotonin re-uptake inhibitors (SSRIs). Dichotomous and continuous measures were calculated using a random effects model, heterogeneity was assessed, and subgroup/sensitivity analyses were done. MAIN RESULTS: Thirty-five short-term (14 weeks or less) RCTs were included in the analysis (4 597 participants). Symptom severity for 17 trials was significantly reduced in the medication groups, relative to placebo (weighted mean difference (WMD) = -5.76, 95% confidence interval (CI)-8.16 - -3.36, N = 2 507). Similarly, summary statistics for responder status from 13 trials demonstrated overall superiority of a variety of medication agents compared with placebo (relative risk (RR) = 1.49, 95% CI: 1.28, 1.73, number needed to treat (NNT) = 4.85, N = 1 272). Medication and placebo response occurred in 59.1% (N = 644) and 38.5% (N = 628) of patients, respectively. Of the medication classes, evidence of treatment efficacy was most convincing for the SSRIs. Medication was also effective in reducing the severity of the PTSD re-experiencing/intrusion, avoidance/numbing, and hyperarousal symptom clusters in 9 trials (N = 1 304). In addition, medication was superior to placebo in reducing comorbid depression and disability. Medication was also less well tolerated than placebo. A narrative review of the 3 maintenance trials suggested that long-term medication may be required in treating PTSD. CONCLUSION: Medication treatments can be effective in treating PTSD, acting to reduce its core symptoms, as well as associated depression and disability, and should be considered as part of the treatment of this disorder. The findings of this review support the status of SSRIs as first-line agents in the pharmacotherapy of PTSD, as well as their value in longterm treatment. However, there remain important gaps in the evidence base, and there is a continued need for more effective agents in the management of PTSD.

Clinical Trials as Topic↗
PubMed2003

Assessing probability of ancestry using simple sequence repeat profiles: applications to maize inbred lines and soybean varieties.

Determining parentage is a fundamental problem in biology and in applications such as identifying pedigrees. Difficulties inferring parentage derive from extensive inbreeding within the population, whether natural or planned; using an insufficient number of hypervariable loci; and from allele mismatches caused by mutation or by laboratory errors that generate false exclusions. Many studies of parentage have been limited to comparisons of small numbers of specific parent-progeny triplets. There have been few large-scale surveys of candidates in which there is no prior knowledge of parentage. We present an algorithm that determines the probability of parentage in circumstances where there is no prior knowledge of pedigree and that is robust in the face of missing data and mistyped data. The focus is parentage of an inbred line having uncertain ancestry. The algorithm is a variation of a previously published hybrid-focused algorithm. We describe the algorithm and demonstrate its performance in determining parentage of 43 inbred varieties of soybean that have been profiled using 236 SSR loci and from seven inbred varieties of maize that were profiled using 70 SSR loci. We include simulations of additional levels of missing and mistyped data to show the algorithm's utility and flexibility.

Data Interpretation, Statistical↗
PubMed2004

New Doppler ultrasound signs improve the non-invasive diagnosis of cirrhosis or severe liver fibrosis.

OBJECTIVES: To determine whether ultrasound and, particularly, new Doppler signs increased the diagnostic accuracy of the most accurate, currently available markers for the diagnosis of cirrhosis or severe fibrosis. METHODS: Thirty-two clinical (n = 4), biochemical (n = 11) and Doppler ultrasound (n = 17) variables were recorded in 106 patients with compensated chronic liver disease. Diagnostic accuracy was evaluated by discriminant analysis; first, globally, using all variables then by stepwise analysis. RESULTS: (A) Diagnosis of cirrhosis. Using Doppler ultrasound, diagnostic accuracy was 92% (95% confidence interval 81-98) globally, and 89% (76-95) with three variables (spleen length, hepatic vein spectrum and maximum portal vein velocity). Based upon clinical signs, diagnostic accuracy was 86% (77-92) globally, and 85% (76-91) with one variable (firm liver). Based upon biochemical parameters, diagnostic accuracy was 80% (70-88) globally, and 81% (72-88) with two variables (hyaluronate and platelet count). Based upon all parameters, diagnostic accuracy was 91% (79-96.5) globally, and 91% (79-96.5) with four variables (firm liver, hyaluronate, platelet and hepatic vein spectrum). On an intention to diagnose basis, Doppler ultrasound provided a lower independent contribution due to missing data. (B) In the diagnosis of severe fibrosis, diagnostic accuracy was 83% (69-92) globally, and 77% (62-87) with one variable. CONCLUSIONS: Cirrhosis can be correctly diagnosed in approximately 90% of patients with compensated chronic liver disease using a few Doppler ultrasound signs including a new sign, the hepatic vein spectrum. Doppler ultrasound could be used for the first line diagnosis and biochemical markers, such as hyaluronate, in patients with missing Doppler ultrasound data.

Adult↗
PubMed1997

Now you see it, now you don't: a comparison of traditional versus random-effects regression models in the analysis of longitudinal follow-up data from a clinical trial.

To illustrate the limitations of commonly used methods of handling missing data when using traditional analysis of variance (ANOVA) models and highlight the relative advantages of random-effects regression models, multiple analytic strategies were applied to follow-up data from a clinical trial. Traditional ANOVA and random-effects models produced similar results when underlying assumptions were met and data were complete. However, analyses based on subsamples, to which investigators would have been limited with traditional models, would have led to different conclusions about treatment effects over time than analyses based on intention-to-treat samples using random-effects regression models. These findings underscore the advantages of models that use all data collected and the importance of complete data collection to minimize sample bias.

Adult↗
PubMed2005

Adult myeloid leukaemia and radon exposure: a Bayesian model for a case-control study with error in covariates.

The possible association between radon exposure in dwellings and adult myeloid leukaemia had been explored in an Italian province by a case-control study. A total of 44 cases and 211 controls were selected from death certificates file. No association had been found in the original study (OR = 0.58 for > 185 vs 80 < or = Bq/cm). Here we reanalyse the data taking into account the measurement error of radon concentration and the presence of missing data. A Bayesian hierarchical model with error in covariates is proposed which allows appropriate imputation of missing values. The general conclusion of no evidence of association with radon does not change, but a negative association is not observed anymore (OR = 0.99 for > 185 vs 80 < or = Bq/cm). After adjusting for residential house radon and gamma radiation, and for the multilevel data structure, geological features of the soil is associated with adult myeloid leukaemia risk (OR = 2.14, 95 per cent Cr.I. 1.0-5.5).

Adult↗
PubMed1998

Magnetic resonance imaging for the investigation of knee injuries: an investigation of preferences.

The conventional approach to the diagnosis and treatment of severe knee injuries is arthroscopy, a minimally invasive surgical procedure. Since arthroscopy is an invasive technique that carries risks, magnetic resonance imaging (MRI) is increasingly being used for diagnosis. MRI is potentially associated with diagnostic and therapeutic 'impacts', in that arthroscopy can be avoided. This paper reports a discrete choice conjoint analysis exercise that assessed the value placed on such 'impacts' by potential patients and investigated the degree to which respondents were willing to trade between process and outcome. The marginal rates of substitution between attributes were estimated. The results suggest that the diagnostic and therapeutic 'impacts' of MRI were valued by many respondents. The study has highlighted a number of important issues for the design and analysis of future health-related conjoint studies, including the use of treatment cost as an attribute, dealing with data from lexicographic respondents, and distinguishing between points of indifference and missing data.

Adult↗
PubMed2004

Interactive Health Communication Applications for people with chronic disease.

BACKGROUND: Interactive Health Communication Applications (IHCAs) are computer-based, usually web-based health information packages for patients that combine information with at least one of social support, decision support, or behaviour change support. These are innovations in health care and their effects on health are uncertain. OBJECTIVES: To assess the effects of IHCAs for people with chronic disease. SEARCH STRATEGY: We designed a four-part search strategy. First, we searched electronic bibliographic databases for published work; second, we searched the grey literature and third, we searched for ongoing and recently completed clinical trials in the appropriate databases. Finally, researchers of included studies were contacted, and reference lists from relevant primary and review articles were followed up. As IHCAs require relatively new technology, the search commenced at 1990 where possible. SELECTION CRITERIA: Randomised controlled trials (RCTs) of Interactive Health Communication Applications for adults and children with chronic disease. DATA COLLECTION AND ANALYSIS: One reviewer screened abstracts. Two reviewers screened all candidate studies to determine eligibility, apply quality criteria, and extract data from included studies. Authors of included RCTs were contacted for missing data. Results of RCTs were pooled using a random effects model and standardised mean differences (SMDs) were calculated to provide net effect sizes. MAIN RESULTS: We screened 24,757 unique citations and retrieved 958 papers for further assessment, yielding 28 RCTs involving 4042 participants. One of these had an inadequate method of concealment of allocation, and sensitivity analyses were performed to determine the effects of including or excluding these data in the meta-analyses. Results in the abstract are from the meta-analyses excluding data from this study.IHCAs were found to have a positive effect on knowledge (SMD 0.49; 95% confidence interval (CI) 0.14 to 0.84) and on social support (SMD 0.47; 95% CI 0.28 to 0.66). IHCAs were found to have no effect on self-efficacy (SMD 0.15; 95% CI -0.13 to 0.43) or behavioural outcomes (SMD -0.09; 95% CI -0.49 to 0.32). IHCAs had a negative effect on clinical outcomes (SMD -0.32; 95% CI -0.63 to -0.02). REVIEWERS' CONCLUSIONS: The number and range of IHCAs is increasing rapidly; however there is a shortage of high quality evaluative data. Consumers who wish to increase their knowledge or social support amongst people with a similar problem may find an IHCA helpful. However, consumers whose primary aim is to achieve optimal clinical outcomes should not use an IHCA at present. Further research is needed to determine the reason for this negative effect on clinical outcomes, whether an optimal IHCA can achieve behaviour change and improved health outcomes, and if so, what are the essential features of such an IHCA, and the extent to which they differ according to patient group or condition.

Retraction of Publication as Topic↗
PubMed2005

Interactive Health Communication Applications for people with chronic disease.

BACKGROUND: Interactive Health Communication Applications (IHCAs) are computer-based, usually web-based, information packages for patients that combine health information with at least one of social support, decision support, or behaviour change support. These are innovations in health care and their effects on health are uncertain. OBJECTIVES: To assess the effects of IHCAs for people with chronic disease. SEARCH STRATEGY: We designed a four-part search strategy. First, we searched electronic bibliographic databases for published work; second, we searched the grey literature; and third, we searched for ongoing and recently completed clinical trials in the appropriate databases. Finally, researchers of included studies were contacted, and reference lists from relevant primary and review articles were followed up. As IHCAs require relatively new technology, the search time period commenced at 1990, where possible, and ran until 31 December 2003. SELECTION CRITERIA: Randomised controlled trials (RCTs) of IHCAs for adults and children with chronic disease. DATA COLLECTION AND ANALYSIS: One reviewer screened abstracts for relevance. Two reviewers screened all candidate studies to determine eligibility, apply quality criteria, and extract data from included studies. Authors of included RCTs were contacted for missing data. Results of RCTs were pooled using random-effects model with standardised mean differences (SMDs) for continuous outcomes and odds ratios for binary outcomes; heterogeneity was assessed using the I(2 )statistic. MAIN RESULTS: We identified 24 RCTs involving 3739 participants which were included in the review.IHCAs had a significant positive effect on knowledge (SMD 0.46; 95% confidence interval (CI) 0.22 to 0.69), social support (SMD 0.35; 95% CI 0.18 to 0.52) and clinical outcomes (SMD 0.18; 95% CI 0.01 to 0.35). Results suggest it is more likely than not that IHCAs have a positive effect on self-efficacy (a person's belief in their capacity to carry out a specific action) (SMD 0.24; 95% CI 0.00 to 0.48). IHCAs had a significant positive effect on continuous behavioural outcomes (SMD 0.20; 95% CI 0.01 to 0.40). Binary behavioural outcomes also showed a positive effect for IHCAs, although this result was not statistically significant (OR 1.66; 95% CI 0.71 to 3.87). It was not possible to determine the effects of IHCAs on emotional or economic outcomes. AUTHORS' CONCLUSIONS: IHCAs appear to have largely positive effects on users, in that users tend to become more knowledgeable, feel better socially supported, and may have improved behavioural and clinical outcomes compared to non-users. There is a need for more high quality studies with large sample sizes to confirm these preliminary findings, to determine the best type and best way to deliver IHCAs, and to establish how IHCAs have their effects for different groups of people with chronic illness.

Adaptation, Psychological↗
PubMedDate not supplied

"Keyhole" method for accelerating imaging of contrast agent uptake.

Magnetic resonance (MR) imaging methods with good spatial and contrast resolution are often too slow to follow the uptake of contrast agents with the desired temporal resolution. Imaging can be accelerated by skipping the acquisition of data normally taken with strong phase-encoding gradients, restricting acquisition to weak-gradient data only. If the usual procedure of substituting zeroes for the missing data is followed, blurring results. Substituting instead reference data taken before or well after contrast agent injection reduces this problem. Volunteer and patient images obtained by using such reference data show that imaging can be usefully accelerated severalfold. Cortical and medullary regions of interest and whole kidney regions were studied, and both gradient- and spin-echo images are shown. The method is believed to be compatible with other acceleration methods such as half-Fourier reconstruction and reading of more than one line of k space per excitation.

Contrast Media↗
PubMed1994

Crossover designs for clinical trials.

I discuss three-period crossover designs for an efficient comparison of two test treatments with special application to clinical trials which often have many practical limitations. In this paper I specify a subset of three-period crossover designs so that the investigators are not left with the problematic two-period two-sequence design, should the trials be terminated after the second period. I show that there is a dramatic reduction in variability for estimating the direct and residual treatment effects in three-period designs compared to two-period designs. I also show that the universally optimal design with ABB and BAA sequences is unsuitable when a complex form of residual effects is suspected, such as the second-order residual effects or treatment by period interactions. The design with ABB, BAA, AAB, and BBA sequences is relatively robust to these uncertain model assumptions. I also discuss missing data problems and conclude that, even with a large proportion of missing values, the three-period design is far more efficient than the two-period design.

Analysis of Variance↗
PubMed2007

Early-life and adult socioeconomic status and inflammatory risk markers in adulthood.

BACKGROUND: Associations between childhood and adult socioeconomic status (SES) and adult levels of inflammatory markers (C-reactive protein [CRP], fibrinogen, white blood cell count [WBC], and von Willebrand factor [vWF]) were examined in the Atherosclerosis Risk in Communities (ARIC) Study cohort. METHODS: A total of 12,681 white and African-American participants provided information on SES (via education and social class) and place of residence in childhood and adulthood. Residences were linked to census data for neighborhood SES information. Multiple imputation was used to impute missing data. Hierarchical and linear regression were used to estimate the effects of SES and possible mediation by adult cardiovascular disease (CVD) risk factors. FINDINGS: Low childhood social class and education were associated with elevated levels of CRP, fibrinogen, WBC, and vWF (increments of 17%, 2%, 4% and 3% for lowest versus highest education in childhood, respectively) among whites. Findings were less consistent among African-Americans. Adult SES was more strongly associated with inflammation than childhood SES. Individual-level SES measures were more consistently associated with inflammation than neighborhood-level measures. Fibrinogen and WBC showed the most consistent associations with SES; the largest changes in inflammation by SES were observed for CRP. Covariate adjustment strongly attenuated these associations. Mediation of the SES-inflammation associations by BMI, smoking and HDL cholesterol (HDL-C) are suggested by these data. CONCLUSION: Low individual- and neighborhood-level SES in childhood and adulthood are associated with modest increments in adult inflammatory burden. These associations may operate through the influence of low SES on traditional CVD risk factors, especially BMI, smoking and HDL-C.

Black or African American↗
PubMed1994

A PC program for classification into one of several groups on the basis of longitudinal data.

A stand-alone, menu-driven PC program, ZCLASS, written in GAUSS386i, for classifying subjects into one of several distinct, existing groups on the basis of longitudinal data is described, illustrated, and made available to interested readers. The program accepts data from studies where common times of measurement are planned, but missing data are accommodated in that one or more measurement sequences may be incomplete.

Anthropometry↗
PubMed1988

Microcomputer application of Bayesean probability testing for the identification of bacteria.

A computer program (BACTID) is described which facilitates the identification of bacteria based on a priori data and Bayesean probability testing. The program is not limited to a specific format, has a short execution time, can be easily applied to a variety of situations, and can be run on almost any microcomputer system operating under either 8-bit CP/M or 16-bit MS-DOS/PC-DOS. Additionally, BACTID (1) is not limited to one type of computer (hardware independent), (2) is not limited by size of the computer's random access (RAM independent), (3) can recognize various data bases matrices (format independent), (4) is able to compensate for missing data and (5) allows for various methods of data entry. The efficacy of the program was checked against a commercially available test system and a 99.34% agreement was obtained. Also, the execution time for a 46 x 21 element data matrix was as little as 3.5 s. These results show that microcomputer identification programs are not only viable alternatives to code book registers, but also offer flexibility which is not found in commercial systems.

Bacteria↗
PubMed2004

The clinical effectiveness of cognitive behaviour therapy: outcome for a large sample of adults treated in routine practice.

There is increasing interest in questions about how far the demonstrated efficacy of psychological therapies in research trials can be translated into clinical effectiveness in routine practice. This paper summarises outcome data from several hundred patients treated with CBT in routine clinical practice in a National Health Service psychology service, and compares their outcomes with some of the published research. Although the data have flaws common in ordinary clinical practice (no untreated controls, missing data, uncontrolled pharmacotherapy, etc.), the analyses suggest that CBT in this context is an effective treatment, albeit with probably not quite such good results as it achieves in research trials. Using clinical significance statistics on standardised measures, about half of the sample reliably improved over a course of therapy, including about a third who recovered to normal range.

Adolescent↗