Lessons in learning gain: insights from a pilot project

‘Learning gain’ has become an increasingly prominent concept in debates about the effectiveness of higher education across OECD countries. In England, interest has been heightened by the Higher Education Funding Council for England (HEFCE)’s major research initiative on learning gain, launched in 2015, and by the new Teaching Excellence Framework which assesses learning and teaching and student outcomes. HEFCE’s novel research initiative has funded a set of experimental projects across the English higher education sector for the first time. This paper presents preliminary findings from one such project at the University of East Anglia (UEA). The project trials and evaluates three approaches to identifying and measuring learning gain using data from cohorts of students across different discipline areas during 2015–2016 and 2016–2017. It builds upon previous work carried out at UEA in developing self-efficacy assessments and applying concept inventories. Student marks provide a simple comparator as a third approach to measuring learning gain

Array-based comparative genomic hybridization analysis reveals chromosomal copy number aberrations associated with clinical outcome in canine diffuse large B-cell lymphoma

Canine Diffuse Large B-cell Lymphoma (cDLBCL) is an aggressive cancer with variable clinical response. Despite recent attempts by gene expression profiling to identify the dog as a potential animal model for human DLBCL, this tumor remains biologically heterogeneous with no prognostic biomarkers to predict prognosis. The aim of this work was to identify copy number aberrations (CNAs) by high-resolution array comparative genomic hybridization (aCGH) in 12 dogs with newly diagnosed DLBCL. In a subset of these dogs, the genetic profiles at the end of therapy and at relapse were also assessed. In primary DLBCLs, 90 different genomic imbalances were counted, consisting of 46 gains and 44 losses. Two gains in chr13 were significantly correlated with clinical stage. In addition, specific regions of gains and losses were significantly associated to duration of remission. In primary DLBCLs, individual variability was found, however 14 recurrent CNAs (>30%) were identified. Losses involving IGK, IGL and IGH were always found, and gains along the length of chr13 and chr31 were often observed (>41%). In these segments, MYC, LDHB, HSF1, KIT and PDGFR alpha are annotated. At the end of therapy, dogs in remission showed four new CNAs, whereas three new CNAs were observed in dogs at relapse compared with the previous profiles. One ex novo CNA, involving TCR, was present in dogs in remission after therapy, possibly induced by the autologous vaccine. Overall, aCGH identified small CNAs associated with outcome, which, along with future expression studies, may reveal target genes relevant to cDLBCL

A single amino acid change A19V in perforin: a novel, frequent predisposing factor to childhood acute lymphoblastic leukemia?

We screened 100 children with acute lymphoblastic leukemia (ALL) to assess the incidence of single amino acid change A91V in perform. Heterozygous A91V was found in 12/100 patients and 5/127 controls (OR, 3.4; 95%CI: 1.15-9.95; p=0.014). A91V is a novel and frequent predisposing factor for childhood ALL

Synthesis of dialkyl ethers by decarboxylation of dialkyl carbonates

The decarboxylation reaction of dialkyl carbonates to give their related ethers was investigated. The reaction was carried out at atmospheric pressure and in the presence of hydrotalcite or basic alumina as catalysts without any solvent. The influence of several reaction parameters on the selectivity was studied (e.g. temperature, amount of catalyst, substrate concentration, solvent). The stability of the catalyst was also investigated. The experimental data for the decarboxylation confirmed that this reaction is complicated by competitive processes, such as dismutation and, in one case, pyrolysis. The results obtained show that in the presence of hydrotalcite as a catalyst, symmetrical dialkyl ethers can be synthesised with yields up to 80%. Dissymmetrical ethers (i.e. methyl alkyl ethers) can be produced with yields up to 80% at high temperature (250 ◦C). The catalyst proved to be fully recyclable in all cases studied, except for the carbonate containing n-octyl moiety

Epigenetic silencing of TFPI-2 in canine diffuse large B-cell lymphoma

Epigenetic modifications are important early events during carcinogenesis. In particular, hypermethylation of CpG islands in the promoter region of tumor suppressor genes is a well-known mechanism of gene silencing that contributes to cancer development and progression. Tissue factor pathway inhibitor 2 (TFPI-2) is a tumor suppressor involved in invasiveness inhibition. Although TFPI-2 transcriptional silencing, through promoter hypermethylation, has been widely reported in several human malignancies, it has never been explored in lymphoma. In the present study TFPI-2 methylation and gene expression have been investigated in canine Diffuse Large B-cell lymphomas (cDLBCL). The methylation level of 23 CpGs located within the TFPI-2 promoter was investigated by bisulfite-specific PCR and next generation amplicon deep sequencing (GS Junior 454, Roche) in 22 cDLBCLs and 9 controls. For the same specimens, TFPI-2 gene expression was assessed by means of Real-time RT-PCR. Sequence analysis clearly demonstrated that TFPI2 is frequently hypermethylated in cDLBCL. Hypermethylation of the TFPI-2 promoter was found in 77% of DLBCLs ( 17 out of 22) and in one normal lymph node. Globally, dogs with DLBCL showed a mean methylation level significantly increased compared to controls (p<0.01) and analysis of hypermethylation by site identified 19 loci out of 23 ( 82%) with mean methylation levels from 2- to 120-fold higher in cDLBCL. Gene expression analysis confirmed a significant down-regulation of TFPI-2 ( p<0.05) in DLBCLs compared with normal lymph nodes, suggesting that TFPI-2 hypermethylation negatively regulates its transcription. In addition, a significant positive correlation ( p<0.01) was found between TFPI-2 methylation levels and age providing the first indication of age-associated epigenetic modifications in canine DLBCL. To conclude, our findings demonstrated that epigenetic dysregulation of TFPI-2, leading to its reduced expression, is frequently detected in canine DLBCL. In the next future, the aberrant TFPI-2 promoter hypermethylation may be considered in association with prognosis and therapy

Mustard carbonates: the effect of the leaving group

The substitution of a chlorine atom with a carbonate moiety in mustard compounds has led to a new class of molecules, namely mustard carbonates that retain the reactivity of the well-know toxic iprites, but are safe for the operator and the environment [1]. In this work, we report the further development in mustard carbonates chemistry.The influence of the leaving group on the anchimeric effect of sulfur mustard carbonates has been investigated both in autoclave and neat conditions. Results have led to enhanced selectivity of the anchimerically driven alkylation, as well as, to the improved and more accessible reaction conditions [2]. On the basis of the best results obtained the greener and efficient one-pot method of anchimericlly aided alkylation through syntesis of 2-(methylthio)ethyl ethyl carbonate in situ has been developed. Besides, a new family of half-mustard carbonate anisotropic electrophiles has been synthesized and their reactivity with aromatic nucleophiles has been investigated. The selectivity between two possible products deriving from the nucleophilic attack on the anysotropic mustard carbonates has been shown to depend on the intensity of the electron-withdrawig effect (combination of –I and –M effects) of substituent on an aromatic nucleophile in the para-position. This is remarkable example of how Green Chemistry can domesticate toxic compounds and open the way for their potential application in both preparative and industrial chemistry

Mustard carbonate analogues: influence of the leaving group

The substitution of a chlorine atom with a carbonate moiety in mustard compounds has led to a new class of molecules, namely mustard carbonates that retain the reactivity of the well-know toxic iprites, but are safe for the operator and the environment [1]. Herein we report the influence of the leaving group on the neighboring effect of sulfur half mustard carbonates (HMCs) usually less reactive than nitrogen ones [2]. Several new 2-(methylthio)ethyl alkyl carbonates have been synthesized and their reactivity has been investigated in both autoclave and neat conditions. The results reactions between the HMCs and phenol performed in autoclave (180 °C, no base, in acetonitrile media) showed that the efficiency of the anchimeric effect is directly dependent on the steric hindrance of the HMC leaving group. The least steric hindered 2-(methylthio)ethyl methyl carbonate gave the methyl (2-phenoxyethyl)sulfane in higher yield, whereas the most steric hindered 2-(methylthio)ethyl t-butyl carbonate did not reacted at all. The influence of the leaving group on the anchimeric effect has been also investigated in neat conditions at 150 °C in the presence of catalytic amount of K2CO3. In this case, due to the absence of the solvent and the presence of the base the reaction is more complicated by transesterification reactions and formation of unwanted products. Interestingly 2-(methylthio)ethyl ethyl carbonate showed to be the most efficient carbonate among the ones studied. This resulted might be ascribed to its ability to free the cyclic intermediate from its molecular cage as intimate ion pair more readily than the other HMCs. Finally, several nucleophiles have been then tested in neat reaction conditions using 2-(methylthio)ethyl ethyl carbonate and a catalytic amount of base. In all cases studied it was observed an almost quantitative anchimeric aided alkylation over SN2 reaction, i.e., formation of ethyl aryl ethers. The best results achieved have led to an enhanced product selectivity, more accessible reaction conditions and a better insight on the reaction mechanism of mustard carbonates

A systematic review of the risk factors for clinical response to opioids for all-age patients with cancer-related pain and presentation of the paediatric STOP pain study

Inter-patient variability in response to opioids is well known but a comprehensive definition of its pathophysiological mechanism is still lacking and, more importantly, no studies have focused on children. The STOP Pain project aimed to evaluate the risk factors that contribute to clinical response and adverse drug reactions to opioids by means of a systematic review and a clinical investigation on paediatric oncological patients

DNA methylation profiling reveals common signatures of tumorigenesis and defines epigenetic prognostic subtypes of canine Diffuse Large B-cell Lymphoma

Epigenetic deregulation is a hallmark of cancer characterized by frequent acquisition of new DNA methylation in CpG islands. To gain insight into the methylation changes of canine DLBCL, we investigated the DNA methylome in primary DLBCLs in comparison with control lymph nodes by genome-wide CpG microarray. We identified 1,194 target loci showing different methylation levels in tumors compared with controls. The hypermethylated CpG loci included promoter, 5'-UTRs, upstream and exonic regions. Interestingly, targets of polycomb repressive complex in stem cells were mostly affected suggesting that DLBCL shares a stem cell-like epigenetic pattern. Functional analysis highlighted biological processes strongly related to embryonic development, tissue morphogenesis and cellular differentiation, including HOX, BMP and WNT. In addition, the analysis of epigenetic patterns and genome-wide methylation variability identified cDLBCL subgroups. Some of these epigenetic subtypes showed a concordance with the clinical outcome supporting the hypothesis that the accumulation of aberrant epigenetic changes results in a more aggressive behavior of the tumor. Collectively, our results suggest an important role of DNA methylation in DLBCL where aberrancies in transcription factors were frequently observed, suggesting an involvement during tumorigenesis. These findings warrant further investigation to improve cDLBCL prognostic classification and provide new insights on tumor aggressiveness