Search

This longitudinal project identified young children at risk of literacy difficulties and asked why some of these children fail to benefit from phonologically based intervention. Reception class children were screened to identify a group at risk of literacy difficulties and a matched group of children not at risk. Profiles were compiled for each child including measures of reading, spelling, memory, rapid naming, vocabulary and phonological awareness. A daily, 15-week, small group intervention was implemented with 67 at-risk children. Those who had not made progress in their literacy following this intervention participated in a second, individually administered intervention. The results indicate that letter knowledge and expressive vocabulary are key factors mediating a child's ability to benefit from a phonologically based intervention. Findings are discussed in the context of a lexical restructuring account of the development of spoken word recognition.

This paper reports on a project aimed at providing skills and resources to support nursery staff in identifying areas of strength and need in 3- to 5-year-old children. The six participating nurseries were all in areas of high socio-economic disadvantage. Staff were trained to administer, score and interpret a wide-ranging screening inventory. Following the assessment of children at nursery entry, staff were given support in developing appropriate programmes of activities to address the weaknesses and build on the strengths identified for individual children. All the children were reassessed following a period of six months. Although time was a major issue, staff were generally positive about the screening process and recognised the worth of early identification and intervention. While 46% of 173 children screened at the start of the project had significant difficulties in some area of development, only 6.9% remained at risk on the screening measure following tailored input. Systematic screening was identified as important for alerting staff to difficulties that might otherwise go unnoticed. (Contains 3 tables and 1 figure.)

It is generally accepted that dyslexia should be identified early for interventions to have maximum effect. However, when children speak English as an additional language (EAL), diagnosis is more complex and there is concern that these children tend to be under-identified. This paper reports a longitudinal study following the development of phonological awareness skills in relation to progress in learning to read with a cohort of British Asian children learning EAL and their monolingual peers. It also sought to determine the usefulness of a measure of phonological skills for the identification of dyslexic-type difficulties in children learning EAL. Analysis revealed that both cohorts achieved similar levels of reading accuracy in school Years 2, 4 and 6, with higher levels of reading comprehension for the monolingual children and faster reading fluency for children learning EAL in each school year. There was a similar pattern of relationships between the reading measures and measures of phonological awareness for both groups of children. However, monolingual children achieved higher levels of rhyme detection and alliteration fluency whilst the children learning EAL achieved faster number naming times. Overall, a phonological assessment battery was useful in identifying reading accuracy related difficulties in both groups of children. However, concerns are raised about the sensitivity of such measures following the introduction of the Literacy Hour. (Contains 9 tables.)

Examines the cognitive-linguistic factors underlying literacy development in monolingual children and children learning English as an additional language (EAL) over a three-year period. Reveals similarities between the two groups of children in the study on reading accuracy, but children learning EAL had lower levels of vocabulary and comprehension at each point in time. Considers implications of the findings for classroom practice. (SG)

Notes that suggestions have been made in the media that tinted lenses may provide a "cure" for developmental dyslexia, and considers how there have been many anecdotal accounts of improvements in reading following their use. Provides an overview of the research into the use of tinted lenses for the amelioration of reading difficulties. (SG)

In the first study of the term "genius", 349 undergraduates nominated three geniuses in 1984, 1991, 1993, 1994, and 1997. Einstein was regarded as a stereotypical genius, while other nominees were subjective and transitory. In the second study, nominated geniuses were agreed to on only 26.2 percent of possible occasions. (Contains references.) (Author/CR)

Ventricular tachyarrhythmias are a leading cause of sudden death. Over the past 40 years, a variety of pharmacological therapies for ventricular tachyarrhythmias have been developed. In large clinical trials, most [...], Carvedilol is one of the most effective beta blockers for preventing ventricular tachyarrhythmias in heart failure, but the mechanisms underlying its favorable antiarrhythmic benefits remain unclear. Spontaneous [Ca.sup.2+] waves, also called store overload-induced [Ca.sup.2+] release (SOICR), evoke ventricular tachyarrhythmias in individuals with heart failure. Here we show that carvedilol is the only beta blocker tested that effectively suppresses SOICR by directly reducing the open duration of the cardiac ryanodine receptor (RyR2). This unique anti-SOICR activity of carvedilol, combined with its beta-blocking activity, probably contributes to its favorable antiarrhythmic effect. To enable optimal titration of carvedilol's actions as a beta blocker and as a suppressor of SOICR separately, we developed a new SOICR-inhibiting, minimally beta-blocking carvedilol analog, VK-II-86. VK-II-86 prevented stress-induced ventricular tachyarrhythmias in RyR2-mutant mice and did so more effectively when combined with either of the selective beta blockers metoprolol or bisoprolol. Combining SOICR inhibition with optimal beta blockade has the potential to provide antiarrhythmic therapy that can be tailored to individual patients.

Author(s): Drosophila 12 Genomes Consortium; Project Leaders; Andrew G. Clark (corresponding author) [1]; Michael B. Eisen (corresponding author) [2, 3]; Douglas R. Smith (corresponding author) [4]; Casey M. Bergman (corresponding [...]

Differentially substituted 1,3-diaryl-substituted allylic cations generated by ionization of the corresponding allylic alcohols in the presence of a Lewis acid has undergone chemoselective and regioselective electrocyclization reactions in order to produce 1-aryl-1H-indenes. An unusual dimerization reaction has occurred to produce a cyclopenta[a]indene by a formal cationic 2[pi]+2[pi] cycloaddition of the allylic cation with the intermediate indene.

The introduction of ring strain in the dienophile, as with moderately strained bicycle[2.2.1]heptenes (norbornene), has enabled three-component Povarov reaction with in situ formed N-arylimines under Lewis acid catalyzed conditions (B[F.sub.3].O[Et.sub.2]). The preference for the formation of exo-exo diastereomic adducts is seen in most cases, but the formation of exo-endo adducts is observed for reactions of ortho- or meta-substituted anilines.

Magnetic resonance imaging (MRI) is a well established diagnostic technique, one from which all patients should be able to benefit, including those with implanted medical devices. This paper describes an experimental and numerical study of the temperature rise near the ends of wires by the radio frequency (rf) field in MRI. These wires simulate long wires which may be part of a medical implant. Temperature rise as a function of time was measured for wires of different lengths and diameters in a phantom exposed to the 64 MHz rf field inside a MRI body coil. For wires with no or thin insulation, the maximal rise was about seven times background for a wire length of 20 cm; wires with longer and shorter lengths exhibited less temperature rise. The temperature rise was greater for wires with thicker insulation. Computer simulations using a quasistatic model are in reasonable agreement with the measurements on shorter wires. It is concluded that medical implants with long conducting lead wires may result in potentially unsafe temperature rise during MRI imaging. © 2000 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Total elbow arthroplasty can be a rewarding operation and is becoming increasingly used in the elderly fracture population. Multiple approaches are represented in the literature and deciding on the best approach is difficult. This review discusses approaches and their reported outcomes, aiming to allow surgeons to make an informed choice about which approach to use. [ABSTRACT FROM AUTHOR]

β-Blockers are a standard treatment for heart failure and cardiac arrhythmias. There are ~30 commonly used β-blockers, representing a diverse class of drugs with different receptor affinities and pleiotropic properties. We reported that among 14 β-blockers tested previously, only carvedilol effectively suppressed cardiac ryanodine receptor (RyR2)-mediated spontaneous Ca2+ waves during store Ca2+ overload, also known as store overload-induced Ca2+ release (SOICR). Given the critical role of SOICR in arrhythmogenesis, it is of importance to determine whether there are other β-blockers that suppress SOICR. Here, we assessed the effect of other commonly used β-blockers on RyR2-mediated SOICR in HEK293 cells, using single-cell Ca2+ imaging. Of the 13 β-blockers tested, only nebivolol, a β-1-selective β-blocker with nitric oxide synthase (NOS)-stimulating action, effectively suppressed SOICR. The NOS inhibitor (N-nitro-Larginine methyl ester) had no effect on nebivolol's SOICR inhibition, and the NOS activator (histamine or prostaglandin E2) alone did not inhibit SOICR. Hence, nebivolol's SOICR inhibition was independent of NOS stimulation. Like carvedilol, nebivolol reduced the opening of single RyR2 channels and suppressed spontaneous Ca2+ waves in intact hearts and catecholaminergic polymorphic ventricular tachycardia (CPVT) in the mice harboring a RyR2 mutation (R4496C). Interestingly, a non-β-blocking nebivolol enantiomer, (l)-nebivolol, also suppressed SOICR and CPVT without lowering heart rate. These data indicate that nebivolol, like carvedilol, possesses a RyR2-targeted action that suppresses SOICR and SOICR-evoked VTs. Thus, nebivolol represents a promising agent for Ca2+-triggered arrhythmias. [ABSTRACT FROM AUTHOR]

Carvedilol is the current β-blocker of choice for suppressing ventricular tachyarrhythmia (VT). However, carvedilol's benefits are dose-limited, attributable to its potent β-blocking activity that can lead to bradycardia and hypotension. The clinically used carvedilol is a racemic mixture of β-blocking S-carvedilol and non-β-blocking R-carvedilol. We recently reported that novel non-β-blocking carvedilol analogues are effective in suppressing arrhythmogenic Ca2+ waves and stress-induced VT without causing bradycardia. Thus, the non-β-blocking R-carvedilol enantiomer may also possess this favourable anti-arrhythmic property. To test this possibility, we synthesized R-carvedilol and assessed its effect on Ca2+ release and VT. Like racemic carvedilol, R-carvedilol directly reduces the open duration of the cardiac ryanodine receptor (RyR2), suppresses spontaneous Ca2+ oscillations in human embryonic kidney (HEK) 293 cells, Ca2+ waves in cardiomyocytes in intact hearts and stress-induced VT in mice harbouring a catecholaminergic polymorphic ventricular tachycardia (CPVT)-causing RyR2 mutation. Importantly, Rcarvedilol did not significantly alter heart rate or blood pressure. Therefore, the non-β-blocking R-carvedilol enantiomer represents a very promising prophylactic treatment for Ca2+ - triggered arrhythmia without the bradycardia and hypotension often associated with racemic carvedilol. Systematic clinical assessments of R-carvedilol as a new anti-arrhythmic agent may be warranted. [ABSTRACT FROM AUTHOR]

Carvedilolis a uniquely effective drug for the treatment of cardiacarrhythmias in patients with heart failure. This activity is in partbecause of its ability to inhibit store-overload-induced calcium release(SOICR) through the RyR2 channel. We describe the synthesis, characterization,and bioassay of ca. 100 compounds based on the carvedilol motif toidentify features that correlate with and optimize SOICR inhibition.A single-cell bioassay was employed on the basis of the RyR2-R4496Cmutant HEK-293 cell line in which calcium release from the endoplasmicreticulum through the defective channel was measured. IC50values for SOICR inhibition were thus obtained. The compounds investigatedcontained modifications to the three principal subunits of carvedilol,including the carbazole and catechol moieties, as well as the linkerchain containing the β-amino alcohol functionality. The SARresults indicate that significant alterations are tolerated in eachof the three subunits. [ABSTRACT FROM AUTHOR]

Carvedilol is one of the most effective beta blockers for preventing ventricular tachyarrhythmias in heart failure, but the mechanisms underlying its favorable antiarrhythmic benefits remain unclear. Spontaneous Ca2+ waves, also called store overload-induced Ca2+ release (SOICR), evoke ventricular tachyarrhythmias in individuals with heart failure. Here we show that carvedilol is the only beta blocker tested that effectively suppresses SOICR by directly reducing the open duration of the cardiac ryanodine receptor (RyR2). This unique anti-SOICR activity of carvedilol, combined with its beta-blocking activity, probably contributes to its favorable antiarrhythmic effect. To enable optimal titration of carvedilol's actions as a beta blocker and as a suppressor of SOICR separately, we developed a new SOICR-inhibiting, minimally beta-blocking carvedilol analog, VK-II-86. VK-II-86 prevented stress-induced ventricular tachyarrhythmias in RyR2-mutant mice and did so more effectively when combined with either of the selective beta blockers metoprolol or bisoprolol. Combining SOICR inhibition with optimal beta blockade has the potential to provide antiarrhythmic therapy that can be tailored to individual patients. [ABSTRACT FROM AUTHOR]