The impact of teaching assistants on pupils

The International Guide to Student Achievement brings together and critically examines the major influences shaping student achievement today

Transcorneal electrical stimulation for the treatment of retinitis pigmentosa: results from the TESOLAUK trial

OBJECTIVE: To explore the impact of weekly transcorneal electrical stimulation (TES) over a 6-month period as a treatment for retinitis pigmentosa (RP). METHODS AND ANALYSIS: A prospective open-label observational trial was carried out assessing weekly TES in participants with RP for a period of 6 months followed by observation for a further 6 months. Clinical examination and investigations were carried out at 3 monthly intervals for a total of 12 months. The primary outcome measure explored safety through a descriptive analysis of adverse effects with secondary outcome measures evaluating structural and functional efficacy. RESULTS: Seven male and seven female participants with RP aged 18-80 years were recruited. TES was well tolerated with no serious adverse events reported. Two participants reported transient foreign body sensation and one participant had discomfort underneath the skin electrode. Following 6 months of TES, best-corrected visual acuity increased by 1.1±1.4 letters in the control arm and 0.93±1.4 letters in the treated arm. Central microperimetry threshold sensitivity rose by 0.02±0.5 decibels (dB) and 0.37±0.4 dB and Goldmann visual field volume by 0.16±0.09 steradians (sr) vs 0.22±0.12 sr for the control and treated eye, respectively. There was no statistical significance seen between eyes following the treatment or observation period. CONCLUSION:: This small open-label clinical trial showed that TES was safe and well tolerated in patients with RP. Visual function measurements at 6 months demonstrated no significant difference between the control and treated eyes. The results justify a larger clinical trial over a longer period of time in order to identify any treatment effect

Longitudinal Study to Assess the Quantitative Use of Fundus Autofluorescence for Monitoring Disease Progression in Choroideremia

BACKGROUND: Characterisation of preserved autofluorescence (PAF) area in choroideremia (CHM) and its validity for monitoring disease progression in clinical trials is of importance. METHODS: Eighty patients with molecularly confirmed CHM were recruited. PAF area was measured manually by 2 graders and half-life was calculated based on exponential decay model. RESULTS: Mean age at baseline and follow-up examination was 38.1 (range, 10-69) and 40.7 (range, 11-70) years. Mean follow-up interval was 29 months (range, 6-104). The median LogMAR visual acuity was 0.10 (OD) and 0.18 (OS). Interobserver repeatability for PAF area was -0.99 to 1.03 mm2 (-6.46 to 6.49% of area). There was a statistically significant relationship between age and rate of PAF area loss (r2 = 0.28, p = 0.012). The half-life for PAF area was 13.7 years (range, 1.7-216.0 years). The correlation between half-life and age was stronger than between half-life and log transformed baseline PAF area, although neither was statistically significant. CONCLUSIONS: The intra- and inter-observer PAF area measurement variability provides a baseline change, which must be overcome in a clinical trial if this metric were to be used. Treatments must slow progression to alter the exponential decay in a timely manner accounting for naturally slow progression patterns

Longitudinal Study to Assess the Quantitative Use of Fundus Autofluorescence for Monitoring Disease Progression in Choroideremia

BACKGROUND: Characterisation of preserved autofluorescence (PAF) area in choroideremia (CHM) and its validity for monitoring disease progression in clinical trials is of importance. METHODS: Eighty patients with molecularly confirmed CHM were recruited. PAF area was measured manually by 2 graders and half-life was calculated based on exponential decay model. RESULTS: Mean age at baseline and follow-up examination was 38.1 (range, 10-69) and 40.7 (range, 11-70) years. Mean follow-up interval was 29 months (range, 6-104). The median LogMAR visual acuity was 0.10 (OD) and 0.18 (OS). Interobserver repeatability for PAF area was -0.99 to 1.03 mm2 (-6.46 to 6.49% of area). There was a statistically significant relationship between age and rate of PAF area loss (r2 = 0.28, p = 0.012). The half-life for PAF area was 13.7 years (range, 1.7-216.0 years). The correlation between half-life and age was stronger than between half-life and log transformed baseline PAF area, although neither was statistically significant. CONCLUSIONS: The intra- and inter-observer PAF area measurement variability provides a baseline change, which must be overcome in a clinical trial if this metric were to be used. Treatments must slow progression to alter the exponential decay in a timely manner accounting for naturally slow progression patterns

Population Selection and Sequencing of Caenorhabditis elegans Wild Isolates Identifies a Region on Chromosome III Affecting Starvation Resistance

To understand the genetic basis of complex traits, it is important to be able to efficiently phenotype many genetically distinct individuals. In the nematode Caenorhabditis elegans, individuals have been isolated from diverse populations around the globe and whole-genome sequenced. As a result, hundreds of wild strains with known genome sequences can be used for genome-wide association studies (GWAS). However, phenotypic analysis of these strains can be laborious, particularly for quantitative traits requiring multiple measurements per strain. Starvation resistance is likely a fitness-proximal trait for nematodes, and it is related to metabolic disease risk in humans. However, natural variation in C. elegans starvation resistance has not been systematically characterized, and precise measurement of the trait is time-intensive. Here, we developed a population-selection-and-sequencing-based approach to phenotype starvation resistance in a pool of 96 wild strains. We used restriction site-associated DNA sequencing (RAD-seq) to infer the frequency of each strain among survivors in a mixed culture over time during starvation. We used manual starvation survival assays to validate the trait data, confirming that strains that increased in frequency over time are starvation-resistant relative to strains that decreased in frequency. Further, we found that variation in starvation resistance is significantly associated with variation at a region on chromosome III. Using a near-isogenic line (NIL), we showed the importance of this genomic interval for starvation resistance. This study demonstrates the feasibility of using population selection and sequencing in an animal model for phenotypic analysis of quantitative traits, documents natural variation of starvation resistance in C. elegans, and identifies a genomic region that contributes to such variation

Long-term trends in tropical cyclone tracks around Korea and Japan in late summer and early fall

This study investigates long-term trends in tropical cyclones (TCs) over the extratropical western North Pacific (WNP) over a period of 35 years (1982-2016). The area analyzed extended across 30-45 degrees N and 120-150 degrees E, including the regions of Korea and Japan that were seriously affected by TCs. The northward migration of TCs over the WNP to the mid-latitudes showed a sharp increase in early fall. In addition, the duration of TCs over the WNP that migrated northwards showed an increase, specifically in early to mid-September. Therefore, more recently, TC tracks have been observed to significantly extend into the mid-latitudes. The recent northward extension of TC tracks over the WNP in early fall was observed to be associated with changes in environmental conditions that were favorable for TC activities, including an increase in sea surface temperature (SST), decrease in vertical wind shear, expansion of subtropical highs, strong easterly steering winds, and an increase in relative vorticity. In contrast, northward migrations of TCs to Korea and Japan showed a decline in late August, because of the presence of unfavorable environmental conditions for TC activities. These changes in environmental conditions, such as SST and vertical wind shear, can be partially associated with the Pacific decadal oscillation

Sustained Effects of Incredible Years as a Preventive Intervention in Preschool Children with Conduct Problems

The present study evaluated preventive effects of the Incredible Years program for parents of preschool children who were at risk for a chronic pattern of conduct problems, in the Netherlands. In a matched control design, 72 parents of children with conduct problems received the Incredible Years program. These families (intervention group) were compared with 72 families who received care as usual (control group). Two years after termination of the intervention, it appeared that observed and selfrated parenting skills were significantly improved in the intervention group. Likewise, in this group, observed child conduct problems showed sustained intervention effects. The decrease in observed critical parenting mediated the decrease in observed child conduct problems over time. In addition, it appeared that parental influence increased over time

C–O–H–S fluids and granitic magma : how S partitions and modifies CO2 concentrations of fluid-saturated felsic melt at 200 MPa

Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Contributions to Mineralogy and Petrology 162 (2011): 849-865, doi:10.1007/s00410-011-0628-1.Hydrothermal volatile-solubility and partitioning experiments were conducted with fluid-saturated haplogranitic melt, H2O, CO2, and S in an internally heated pressure vessel at 900°C and 200 MPa; three additional experiments were conducted with iron-bearing melt. The run-product glasses were analyzed by electron microprobe, FTIR, and SIMS; and they contain ≤ 0.12 wt% S, ≤ 0.097 wt.% CO2, and ≤ 6.4 wt.% H2O. Apparent values of log ƒO2 for the experiments at run conditions were computed from the [(S6+)/(S6++S2-)] ratio of the glasses, and they range from NNO-0.4 to NNO+1.4. The C-O-H-S fluid compositions at run conditions were computed by mass balance, and they contained 22-99 mol% H2O, 0-78 mol% CO2, 0-12 mol% S, and < 3 wt% alkalis. Eight S-free experiments were conducted to determine the H2O and CO2 concentrations of melt and fluid compositions and to compare them with prior experimental results for C-O-H fluid-saturated rhyolite melt, and the agreement is excellent. Sulfur partitions very strongly in favor of fluid in all experiments, and the presence of S modifies the fluid compositions, and hence, the CO2 solubilities in coexisting felsic melt. The square of the mole fraction of H2O in melt increases in a linear fashion, from 0.05-0.25, with the H2O concentration of the fluid. The mole fraction of CO2 in melt increases linearly, from 0.0003-0.0045, with the CO2 concentration of C-O-H-S fluids. Interestingly, the CO2 concentration in melts, involving relatively reduced runs (log ƒO2 ≤ NNO+0.3) that contain 2.5-7 mol% S in the fluid, decreases significantly with increasing S in the system. This response to the changing fluid composition causes the H2O and CO2 solubility curve for C-O-H-S fluid-saturated haplogranitic melts at 200 MPa to shift to values near that modeled for C-O-H fluid-saturated, S-free rhyolite melt at 150 MPa. The concentration of S in haplogranitic melt increases in a linear fashion with increasing S in C-O-H-S fluids, but these data show significant dispersion that likely reflects the strong influence of ƒO2 on S speciation in melt and fluid. Importantly, the partitioning of S between fluid and melt does not vary with the (H2O/H2O+CO2) ratio of the fluid. The fluid-melt partition coefficients for H2O, CO2, and S and the atomic (C/S) ratios of the run-product fluids are virtually identical to thermodynamic constraints on volatile partitioning and the H, S, and C contents of pre-eruptive magmatic fluids and volcanic gases for subduction-related magmatic systems thus confirming our experiments are relevant to natural eruptive systems.This research was supported in part by National Science Foundation awards EAR 0308866 and EAR-0836741 to J.D.W

Pain and analgesic use associated with skeletal-related events in patients with advanced cancer and bone metastases

PURPOSE: Bone metastases secondary to solid tumors increase the risk of skeletal-related events (SREs), including the occurrence of pathological fracture (PF), radiation to bone (RB), surgery to bone (SB), and spinal cord compression (SCC). The aim of this study was to evaluate the impact of SREs on patients' pain, analgesic use, and pain interference with daily functioning. METHODS: Data were combined from patients with solid tumors and bone metastases who received denosumab or zoledronic acid across three identically designed phase 3 trials (N = 5543). Pain severity (worst pain) and pain interference were assessed using the Brief Pain Inventory at baseline and each monthly visit. Analgesic use was quantified using the Analgesic Quantification Algorithm. RESULTS: The proportion of patients with moderate/severe pain and strong opioid use generally increased in the 6 months preceding an SRE and remained elevated, while they remained relatively consistent over time in patients without an SRE. Regression analysis indicated that all SRE types were significantly associated with an increased risk of progression to moderate/severe pain and strong opioid use. PF, RB, and SCC were associated with significantly greater risk of pain interference overall. Results were similar for pain interference with emotional well-being. All SRE types were associated with significantly greater risk of pain interference with physical function. CONCLUSIONS: SREs are associated with increased pain and analgesic use in patients with bone metastases. Treatments that prevent SREs may decrease pain and the need for opioid analgesics and reduce the impact of pain on daily functioning