Riflettere sulla grammatica a scuola: una ricerca sul soggetto

The paper discusses some preliminary results of the research project GRASS - Grammar Reflection at School: Syntactic Subject, which involved 444 junior and senior students from lower to higher education grades and 16 teachers. Starting from some general remarks on the current state of grammar teaching in the Italian school system, particularly critical as far as real speech, discourse and metalinguistic awareness are concerned, the paper highlights and discusses three main critical issues: a)the confusion between (con)textual reference and grammatical function, well attested by thediverse and incongruous ways used by the respondents to identify and represent the subject of sentences from a text; b) the pupils’ and students’ grammaticality judgements on verb and subject agreement, especially in cases of semantic/syntactic mismatch; c) the relation between the respondents’ explicit definitions of grammatical subject and the emerging underlying notions that characterize the different stages of Italian education as far as primary vs. secondary schools are concerned. Finally, some conclusions are drawn on the possible outcomes that this type of research can have in terms of teachers’ training and teaching practices.In questo articolo vengono presentati i primi risultati della ricerca GRASS (Riflessione Grammaticale a Scuola: il Soggetto Sintattico), che ha coinvolto 444 tra alunni e studenti dalla scuola primaria al primo anno di università e 16 insegnanti. Muovendo da alcune riflessioni generali sull’insegnamento della grammatica nella scuola italiana, la cui criticità sta, fra l’altro, nella scarsa considerazione degli usi linguistici reali nello sviluppo della riflessione metalinguistica, l’articolo tratta nello specifico alcuni aspetti emersi dalla ricerca. Innanzitutto, la confusione tra funzione grammaticale e referenza, ben testimoniata dalle espressioni incongrue e idiosincratiche usate dagli informanti per esplicitare i soggetti individuati in un testo. Poi, i giudizi di grammaticalità rispetto a frasi dell’italiano contenenti casi problematici di accordo verbo-soggetto. Infine, l’analisi delle definizioni esplicite di soggetto fornite da alunni e studenti, che forniscono indicazioni sulla sottostante nozione di soggetto così come viene appresa nel corso della scolarizzazione. Il saggio si conclude con alcune riflessioni su come ricerche di questo tipo possano avere ricadute in termini di formazione degli insegnanti e di pratiche didattiche

Neoadjuvant trials in early breast cancer: pathological response at surgery and correlation to longer term outcomes - what does it all mean?

BACKGROUND: Neoadjuvant breast cancer trials are important for speeding up the introduction of new treatments for patients with early breast cancer and for the highly productive translational research which they facilitate. Meta-analysis of trial data shows clear correlation between pathological response at surgery after neoadjuvant chemotherapy and longer-term outcomes at an individual patient level. However, this does not appear to be present on individual trial level analysis, when correlating improved outcome for the investigational arm for the primary endpoint (pathological response) with longer-term outcomes. DISCUSSION: The correlation between pathological response and longer-term outcomes in trials is dependent on many factors. These include definitions of pathological response, both complete and partial; assessment methods for pathological response at surgery; subtype and prognosis of breast cancer at diagnosis; number of patients recruited; adjuvant treatments; the mechanism of action of the investigational drug; the length of follow-up at the time of reporting; the definitions used in longer-term outcomes analysis; clonal heterogeneity; and new adaptive trial designs with additional neo/adjuvant treatments. Future developments of neoadjuvant breast cancer trials are discussed. With so many factors influencing the correlation of longer-term outcomes for trial-level data, we conclude that the main focus of neoadjuvant trials should remain the primary endpoint of pathological response. Neoadjuvant breast cancer trials are very important investigational studies that will continue to increase our understanding of the disease and offer the potential of more rapid introduction of new treatments for women with high-risk early breast cancer. In the future, we are likely to see both novel trial designs adopted in the neoadjuvant context and modifications of neo/adjuvant treatments for pathological non-responders within clinical trials. Both of these have the intention of improving longer-term outcomes for patients who do not have a good pathological response to first-line neoadjuvant treatment. If successful, these developments are likely to reduce further any positive correlation between pathological response and longer-term outcomes

Decline in Antigenicity of Tumor Markers by Storage Time Using Pathology Sections Cut From Tissue Microarrays.

Sectioning a whole tissue microarrray (TMA block) and storing the sections maximizes the number of sections obtained, but may impair the antigenicity of the stored sections. We have investigated the impact of TMA section storage on antigenicity. First, we reexamined existing TMA data to determine whether antigenicity in stored sections changes over time. Component scores for each marker, based on cellular compartment of staining and score-type, were evaluated separately. Residual components scores adjusted for grade, tumor size, and node positivity, were regressed on the number of days storage to evaluate the effect of storage time. Storage time ranged from 2 to 1897 days, and the mean change in antigenicity per year ranged from -0.88 (95% confidence interval, -1.11 to -0.65) to 0.035 (95% confidence interval, 0.016-0.054). Further analysis showed no significant improvement in the fit of survival models if storage time adjusted scores were included in the models rather than unadjusted scores. We then compared 3 ways of processing TMA sections after cutting-immediate staining, staining after 1 year, and staining after 1 year coated in wax-on the immunohistochemistry results for: progesterone receptor, a routinely used, robust antibody, and MKI67, which is generally considered less robust. The progesterone receptor scores for stored sections were similar to those for unstored sections, whereas the MKI67 scores for stored sections were substantially different to those for unstored sections. Wax coating made little difference to the results. Biomarker antigenicity shows a small decline over time that is unlikely to have an important effect on studies of prognostic biomarkers.We acknowledge the SEARCH team, the National Cancer Registration Service Eastern Office and Information Centre, the Histopathology Core Facility at the CRUK Cambridge Research Institute for immunohistochemical staining and digital image acquisition and the Human Research Tissue Bank, Cambridge University Hospitals NHS Foundation Trust. This work was funded through a programme grant from Cancer Research UK (C490/A10119, C490/A10124 and C490/A16561) and funding from the NIHR Biomedical Research Centre.This is the final version of the article. It was first published by Lippincott Williams & Wilkins at http://dx.doi.org/10.1097/PAI.000000000000017

Screening Performance of Edmonton Symptom Assessment System in Kidney Transplant Recipients

An average prevalence of 35% for psychiatric comorbidity has been reported in kidney transplant recipients (KTRs) and an even higher prevalence of other psychosocial syndromes, as defined by the Diagnostic Criteria for Psychosomatic Research (DCPR), has also been found in this population. Consequently, an easy, simple, rapid psychiatric tool is needed to measure physical and psychological symptoms of distress in KTRs. Recently, the Edmonton Symptom Assessment System (ESAS), a pragmatic patient-centred symptom assessment tool, was validated in a single cohort of KTRs. The aims of this study were: to test the screening performances of ESAS for the International Classification of Diseases-10th Revision (ICD-10) psychiatric diagnoses in KTRs; to investigate the optimal cut-off points for ESAS physical, psychological and global subscales in detecting ICD-10 psychiatric diagnoses; and to compare ESAS scores among KTR with ICD-10 diagnosis and DCPR diagnosis. 134 KTRs were evaluated and administered the MINI International Neuropsychiatric Interview 6.0 and the DCPR Interview. The ESAS and Canadian Problem Checklist (CPC) were given as self-report instruments to be filled in and were used to examine the severity of physical and psychological symptoms and daily-life problems. The physical distress sub-score (ESAS-PHYS), psychological distress sub-score (ESAS-PSY) and global distress score (ESAS-TOT) were obtained by summing up scores of six physical symptoms, four psychological symptoms and all single ESAS symptoms, respectively. Routine biochemistry, immunosuppressive agents, socio-demographic and clinical data were collected. Receiving Operating Characteristic (ROC) analysis was used to examine the ability of the ESAS emotional distress (DT) item, ESAS-TOT, ESAS-PSY and ESAS-PHYS, to detect psychiatric cases defined by using MINI6.0. The area under the ROC curve for ESAS-TOT, ESAS-PHYS, ESAS-PSY and DT item were 0.85, 0.73, 0.89, and 0.77, respectively. The DT item, ESAS-TOT and ESAS-PSY optimal cut-off points were 654 (sensitivity 0.74, specificity 0.73), 6520 (sensitivity 0.85, specificity 0.74) and 6512 (sensitivity 0.85, specificity 0.80), respectively. No valid ESAS-PHYS cut-off was found (sensitivity <0.7, specificity <0.7). Thirty-nine (84.8%) KTRs with ICD-10 diagnosis did exceed both ESAS-TOT and ESAS-PSY cut-offs. Higher scores on the ESAS symptoms (except shortness of breath and lack of appetite) and on the CPC problems were found for ICD-10 cases and DCRP cases than for ICD-10 no-cases and DCPR no-cases. This study shows that ESAS had an optimal screening performance (84.8%) to identify ICD-10 psychiatric diagnosis, evaluated with MINI; furthermore, ESAS-TOT and ESAS-PSY cut-off points could provide a guide for clinical symptom management in KTRs

Inclusion of KI67 significantly improves performance of the PREDICT prognostication and prediction model for early breast cancer.

BACKGROUND: PREDICT (http://www.predict.nhs.uk) is a prognostication and treatment benefit tool for early breast cancer (EBC). The aim of this study was to incorporate the prognostic effect of KI67 status in a new version (v3), and compare performance with the Predict model that includes HER2 status (v2). METHODS: The validation study was based on 1,726 patients with EBC treated in Nottingham between 1989 and 1998. KI67 positivity for PREDICT is defined as >10% of tumour cells staining positive. ROC curves were constructed for Predict models with (v3) and without (v2) KI67 input. Comparison was made using the method of DeLong. RESULTS: In 1274 ER+ patients the predicted number of events at 10 years increased from 196 for v2 to 204 for v3 compared to 221 observed. The area under the ROC curve (AUC) improved from 0.7611 to 0.7676 (p=0.005) in ER+ patients and from 0.7546 to 0.7595 (p=0.0008) in all 1726 patients (ER+ and ER-). CONCLUSION: Addition of KI67 to PREDICT has led to a statistically significant improvement in the model performance for ER+ patients and will aid clinical decision making in these patients. Further studies should determine whether other markers including gene expression profiling provide additional prognostic information to that provided by PREDICT.SEARCH was funded through a programme grant from Cancer Research UK (C490/A10124) and this work is supported by the UK National Institute for Health Research Biomedical Research Centre at the University of Cambridge.This is the final version of the article. It first appeared from BioMed Central via http://dx.doi.org/10.1186/1471-2407-14-90

Reflecting on grammar at school: a research on the subject

The paper discusses some preliminary results of the research project GRASS - Grammar Reflection at School: Syntactic Subject, which involved 444 junior and senior students from lower to higher education grades and 16 teachers. Starting from some general remarks on the current state of grammar teaching in the Italian school system, particularly critical as far as real speech, discourse and metalinguistic awareness are concerned, the paper highlights and discusses three main critical issues: a)the confusion between (con)textual reference and grammatical function, well attested by thediverse and incongruous ways used by the respondents to identify and represent the subject of sentences from a text; b) the pupils’ and students’ grammaticality judgements on verb and subject agreement, especially in cases of semantic/syntactic mismatch; c) the relation between the respondents’ explicit definitions of grammatical subject and the emerging underlying notions that characterize the different stages of Italian education as far as primary vs. secondary schools are concerned. Finally, some conclusions are drawn on the possible outcomes that this type of research can have in terms of teachers’ training and teaching practices

Familial relative risks for breast cancer by pathological subtype: a population-based cohort study.

INTRODUCTION: The risk of breast cancer to first degree relatives of breast cancer patients is approximately twice that of the general population. Breast cancer, however, is a heterogeneous disease and it is plausible that the familial relative risk (FRR) for breast cancer may differ by the pathological subtype of the tumour. The contribution of genetic variants associated with breast cancer susceptibility to the subtype-specific FRR is still unclear. METHODS: We computed breast cancer FRR for subtypes of breast cancer by comparing breast cancer incidence in relatives of breast cancer cases from a population-based series with known estrogen receptor (ER), progesterone receptor (PR) or human epidermal growth factor receptor 2 (HER2) status with that expected from the general population. We estimated the contribution to the FRR of genetic variants associated with breast cancer susceptibility using subtype-specific genotypic relative risks and allele frequencies for each variant. RESULTS: At least one marker was measured for 4,590 breast cancer cases, who reported 9,014 affected and unaffected first-degree female relatives. There was no difference between the breast cancer FRR for relatives of patients with ER-negative (FRR = 1.78, 95% confidence intervals (CI): 1.44 to 2.11) and ER-positive disease (1.82, 95% CI: 1.67 to 1.98), P = 0.99. There was some suggestion that the breast cancer FRR for relatives of patients with ER-negative disease was higher than that for ER-positive disease for ages of the relative less than 50 years old (FRR = 2.96, 95% CI: 2.04 to 3.87; and 2.05, 95% CI: 1.70 to 2.40 respectively; P = 0.07), and that the breast cancer FRR for relatives of patients with ER-positive disease was higher than for ER-negative disease when the age of the relative was greater than 50 years (FRR = 1.76, 95% CI: 1.59 to 1.93; and 1.41, 95% CI: 1.08 to 1.74 respectively, P = 0.06). We estimated that mutations in BRCA1 and BRCA2 explain 32% of breast cancer FRR for relatives of patients with ER-negative and 9.4% of the breast cancer FRR for relatives of patients with ER-positive disease. Twelve recently identified common breast cancer susceptibility variants were estimated to explain 1.9% and 9.6% of the FRR to relatives of patients with ER-negative and ER-positive disease respectively. CONCLUSIONS: FRR for breast cancer was significantly increased for both ER-negative and ER-positive disease. Including receptor status in conjunction with genetic status may aid risk prediction in women with a family history.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Imaging mass cytometry and multiplatform genomics define the phenogenomic landscape of breast cancer

Genomic alterations shape cell phenotypes and the structure of tumor ecosystems in poorly defined ways. To investigate these relationships, we used imaging mass cytometry to quantify the expression of 37 proteins with subcellular spatial resolution in 483 tumors from the METABRIC cohort. Single-cell analysis revealed cell phenotypes spanning epithelial, stromal and immune types. Distinct combinations of cell phenotypes and cell–cell interactions were associated with genomic subtypes of breast cancer. Epithelial luminal cell phenotypes separated into those predominantly impacted by mutations and those affected by copy number aberrations. Several features of tumor ecosystems, including cellular neighborhoods, were linked to prognosis, illustrating their clinical relevance. In summary, systematic analysis of single-cell phenotypic and spatial correlates of genomic alterations in cancer revealed how genomes shape both the composition and architecture of breast tumor ecosystems and will enable greater understanding of the phenotypic impact of genomic alterations

Inter- and Intra-Observer Agreement of PD-L1 SP142 Scoring in Breast Carcinoma:A Large Multi-Institutional International Study

The assessment of PD-L1 expression in TNBC is a prerequisite for selecting patients for immunotherapy. The accurate assessment of PD-L1 is pivotal, but the data suggest poor reproducibility. A total of 100 core biopsies were stained using the VENTANA Roche SP142 assay, scanned and scored by 12 pathologists. Absolute agreement, consensus scoring, Cohen's Kappa and intraclass correlation coefficient (ICC) were assessed. A second scoring round after a washout period to assess intra-observer agreement was carried out. Absolute agreement occurred in 52% and 60% of cases in the first and second round, respectively. Overall agreement was substantial (Kappa 0.654-0.655) and higher for expert pathologists, particularly on scoring TNBC (6.00 vs. 0.568 in the second round). The intra-observer agreement was substantial to almost perfect (Kappa: 0.667-0.956), regardless of PD-L1 scoring experience. The expert scorers were more concordant in evaluating staining percentage compared with the non-experienced scorers (R2 = 0.920 vs. 0.890). Discordance predominantly occurred in low-expressing cases around the 1% value. Some technical reasons contributed to the discordance. The study shows reassuringly strong inter- and intra-observer concordance among pathologists in PD-L1 scoring. A proportion of low-expressors remain challenging to assess, and these would benefit from addressing the technical issues, testing a different sample and/or referring for expert opinions