The Principals We Hire for Today’s Schools: Voices of Superintendents

The purpose of this study was to identify superintendents’ perceptions of the characteristics of and abilities needed by successful principals in today’s schools. In addition, identification of superintendents’ concerns relative to the principals they hire was solicited

Medication errors and processes to reduce them in care homes in the United Kingdom: a scoping review

Medicines-related incidents are a leading cause of preventable harm across all patient groups, including care home residents. Despite national guidance, there is little information on assessing medication error rates and evaluating changes to reduce them. This review explored the scientific and grey literature on medicines-related incidents, causation and evaluation of changes in care homes in the United Kingdom. The research identified 2951 documents, 32 analysed; some of them covered more than one area. Seven reported rate and causes, eleven causes, eleven made recommendations, and four reported the evaluation of changes to processes and systems. Three areas emerged; 1) medicines-related incident rates ranged between 1% and 38%, 2) incident rates increased where formulations were not tablets or capsules ranging from 12% to 50% depending on the formulation, 3) three evaluations of changes aimed at reducing medicine incidents. Therefore, information on medicines-related incidents in care homes is available, but not systematically described

Regulatory T Cell Responses in Participants with Type 1 Diabetes after a Single Dose of Interleukin-2: A Non-Randomised, Open Label, Adaptive Dose-Finding Trial

BACKGROUND: Interleukin-2 (IL-2) has an essential role in the expansion and function of CD4+ regulatory T cells (Tregs). Tregs reduce tissue damage by limiting the immune response following infection and regulate autoreactive CD4+ effector T cells (Teffs) to prevent autoimmune diseases, such as type 1 diabetes (T1D). Genetic susceptibility to T1D causes alterations in the IL-2 pathway, a finding that supports Tregs as a cellular therapeutic target. Aldesleukin (Proleukin; recombinant human IL-2), which is administered at high doses to activate the immune system in cancer immunotherapy, is now being repositioned to treat inflammatory and autoimmune disorders at lower doses by targeting Tregs. METHODS AND FINDINGS: To define the aldesleukin dose response for Tregs and to find doses that increase Tregs physiologically for treatment of T1D, a statistical and systematic approach was taken by analysing the pharmacokinetics and pharmacodynamics of single doses of subcutaneous aldesleukin in the Adaptive Study of IL-2 Dose on Regulatory T Cells in Type 1 Diabetes (DILT1D), a single centre, non-randomised, open label, adaptive dose-finding trial with 40 adult participants with recently diagnosed T1D. The primary endpoint was the maximum percentage increase in Tregs (defined as CD3+CD4+CD25highCD127low) from the baseline frequency in each participant measured over the 7 d following treatment. There was an initial learning phase with five pairs of participants, each pair receiving one of five pre-assigned single doses from 0.04 × 106 to 1.5 × 106 IU/m2, in order to model the dose-response curve. Results from each participant were then incorporated into interim statistical modelling to target the two doses most likely to induce 10% and 20% increases in Treg frequencies. Primary analysis of the evaluable population (n = 39) found that the optimal doses of aldesleukin to induce 10% and 20% increases in Tregs were 0.101 × 106 IU/m2 (standard error [SE] = 0.078, 95% CI = -0.052, 0.254) and 0.497 × 106 IU/m2 (SE = 0.092, 95% CI = 0.316, 0.678), respectively. On analysis of secondary outcomes, using a highly sensitive IL-2 assay, the observed plasma concentrations of the drug at 90 min exceeded the hypothetical Treg-specific therapeutic window determined in vitro (0.015-0.24 IU/ml), even at the lowest doses (0.040 × 106 and 0.045 × 106 IU/m2) administered. A rapid decrease in Treg frequency in the circulation was observed at 90 min and at day 1, which was dose dependent (mean decrease 11.6%, SE = 2.3%, range 10.0%-48.2%, n = 37), rebounding at day 2 and increasing to frequencies above baseline over 7 d. Teffs, natural killer cells, and eosinophils also responded, with their frequencies rapidly and dose-dependently decreased in the blood, then returning to, or exceeding, pretreatment levels. Furthermore, there was a dose-dependent down modulation of one of the two signalling subunits of the IL-2 receptor, the β chain (CD122) (mean decrease = 58.0%, SE = 2.8%, range 9.8%-85.5%, n = 33), on Tregs and a reduction in their sensitivity to aldesleukin at 90 min and day 1 and 2 post-treatment. Due to blood volume requirements as well as ethical and practical considerations, the study was limited to adults and to analysis of peripheral blood only. CONCLUSIONS: The DILT1D trial results, most notably the early altered trafficking and desensitisation of Tregs induced by a single ultra-low dose of aldesleukin that resolves within 2-3 d, inform the design of the next trial to determine a repeat dosing regimen aimed at establishing a steady-state Treg frequency increase of 20%-50%, with the eventual goal of preventing T1D. TRIAL REGISTRATION: ISRCTN Registry ISRCTN27852285; ClinicalTrials.gov NCT01827735.This is the final version of the article. It first appeared from the Public Library of Science via http://dx.doi.org/10.1371/journal.pmed.100213

An experimental study of the effects of pictures on the literal comprehension of second grade readers

The purpose of the study was to investigate the effect of pictures on the literal reading comprehension of average second graders. The study attempted to discover whether or not there were differences in comprehension when second graders read in three alternate reading conditions: text without pictures (T), text with pictures (TP), and a page of text alternating with a picture page (TAP). The study also attempted to discover whether possible differences in comprehension were more significant for either average or above-average readers.In order to measure differences in amount of comprehension in the three reading conditions, the researcher constructed an instrument consisting of three comparable passages, pictures corresponding to the passages, and ten questions covering the content of each passage. Each subject was asked to read three different passages in three different reading conditions. The ten questions were asked after each of the passages was read. The scores from the comprehension questions became the raw data of the study.The data were analyzed in a 3X3X2 Factorial Analysis of Variance. The factors were reading condition with three levels (T. TP, and TAP), three orders of presentation of the passages, and reading ability with two levels (average and above-average readers).Results indicated that all subjects comprehended equal amounts of content in the three reading conditions (F=.34 at .71 probability). Further, both average and above-average readers were equally unaffected by the presence of pictures in their reading materials (F=.17 at .84 probability).An implication of the study is that teachers should clarify their reason for using pictures in beginning reading instruction. Although pictures may prove to be helpful in fulfilling various affective instructional purposes such as building interest in reading, the pictures do not seem to be a valid method of increasing literal reading comprehension.Thesis (D. Ed.