Capturing the sociomateriality of digital literacy events

This paper discusses a method of collecting and analysing multimodal data during classroom-based digital literacy research. Drawing on reflections from two studies, the authors discuss theoretical and methodological implications encountered in the collection, transcription and presentation of such data. Following an ethnomethodological framework that co-develops theory and methodology, the studies capture digital literacy activities as real-time screen recordings, with embedded video recordings of participants’ movements and vocalisations around the tasks during writing. The result is a multimodal rendition of digital literacy events on- and off-screen, allowing linguistic and multimodal transcriptions to capture the complexity of the data in a format amenable to analysis. Acquiring such data allowed for the development of detailed analyses of digital literacy events in the classroom, including interaction that would otherwise have escaped standard ethnography and video analysis, through sensibilities that approach social and material items without a priori hierarchies. This leads us to a ‘performative’ notion of digital literacies and an analytic methodology that is useful for researchers paying greater attention to the sociomaterial assemblages in which digital literacy events unfold

Targeted imaging of colorectal dysplasia in living mice with fluorescence microendoscopy

We validate specific binding activity of a fluorescence-labeled peptide to colorectal dysplasia in living mice using a miniature, flexible, fiber microendoscope that passes through the instrument channel of an endoscope. The microendoscope delivers excitation light at 473 nm through a fiber-optic bundle with outer diameter of 680 µm to collect en face images at 10 Hz with 4 µm lateral resolution. We applied the FITC-labeled peptide QPIHPNNM topically to colonic mucosa in genetically engineered mice that spontaneously develop adenomas. More than two-fold greater fluorescence intensity was measured from adenomas compared to adjacent normal-appearing mucosa. Images of adenomas showed irregular morphology characteristic of dysplasia

Застосування зворотних залежностей у математичних моделях складних об’єктів та систем

Представлено метод побудови апроксимуючих поліноміальних функцій багатьох змінних, який засновано на використанні в поліномах від’ємних степенів та застосуванні до поліномів обмеження на сумарну величину ступеня добутку змінних. Запропоновано використання штрафної функції на кількість членів полінома. Експериментальним шляхом отримано оптимальну величину коефіцієнта запропонованої штрафної функції.Представлен метод построения аппроксимирующих полиномиальных функций многих переменных, основанный на использовании в полиномах отрицательных степеней и применении к полиномам ограничения на суммарную величину степени произведения переменных. Предложено использование штрафной функции на количество членов полинома. Экспериментальным путем получена оптимальная величина коэффициента предложенной штрафной функции.A method of constructing approximating polynomials functions of many variables, based on the use of the negative degrees in polynomials and the application of the limitation on the total value of the product variable to polynoms is presented. The usage of the penalty function for the number of polynomial members is suggested. The optimum value of the proposed penalty functions coefficient is experimentally obtained

Inhibition of EGFR, HER2, and HER3 signalling in patients with colorectal cancer wild-type for BRAF, PIK3CA, KRAS, and NRAS (FOCUS4-D): a phase 2–3 randomised trial

Background: A substantial change in trial methodology for solid tumours has taken place, in response to increased understanding of cancer biology. FOCUS4 is a phase 2–3 trial programme testing targeted agents in patients with advanced colorectal cancer in molecularly stratified cohorts. Here, we aimed to test the hypothesis that combined inhibition of EGFR, HER2, and HER3 signalling with the tyrosine kinase inhibitor AZD8931 will control growth of all wild-type tumours. Methods: In FOCUS4-D, we included patients from 18 hospitals in the UK with newly diagnosed advanced or metastatic colorectal cancer whose tumour was wild-type for BRAF, PIK3CA, KRAS, and NRAS. After 16 weeks of first-line therapy, patients with stable or responding tumours were randomised to oral AZD8931 (40 mg twice a day) or placebo. Randomisation was done by minimisation with a random element of 20%, minimisation by hospital site, site of primary tumour, WHO performance status, 16-week CT scan result, number of metastatic sites, and first-line chemotherapy regimen. The primary outcome was progression-free-survival. CT scans were assessed by local radiologists according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. Preplanned interim analyses were assessed per protocol and were agreed using multiarm multistage (MAMS) trial design methodology triggered by occurrence of progression-free survival events in the placebo group. The final analysis was assessed by intention to treat. This trial is registered at , ISRCTN 90061546. Findings: Between July 7, 2014, and March 7, 2016, 32 patients were randomised to study treatment, 16 to AZD8931 and 16 to placebo. At the first preplanned interim analysis (March, 2016), the independent data monitoring committee (IDMC) recommended closure of FOCUS4-D because of a lack of activity. At the final analysis (Aug 1, 2016), 31 patients had had a progression-free survival event (15 with AZD8931 and 16 with placebo). Median progression-free survival was 3·48 months (95% CI 1·51–5·09) in the placebo group and 2·96 months (1·94–5·62) in the AZD8931 group. No progression-free survival benefit of AZD8931 compared with placebo was noted (hazard ratio [HR] 1·10, 95% CI 0·47–3·57; p=0·95). The most common grade 3 adverse event in the AZD8931 group was skin rash (three [20%] of 15 patients with available data vs none of 16 patients in the placebo group), and in the placebo group it was diarrhoea (one [7%] vs one [6%]). No grade 4 adverse events were recorded and no treatment-related deaths were reported. Interpretation: The MAMS trial design for FOCUS4 has shown efficiency and effectiveness in trial outcome delivery, informing the decision to proceed or stop clinical evaluation of a targeted treatment within a molecularly defined cohort of patients. The overarching FOCUS4 trial is now aiming to open a replacement arm in the cohort with all wild-type tumours. Funding: Medical Research Council (MRC) and National Institute for Health Research (NIHR) Efficacy and Mechanism Evaluation programme, Cancer Research UK, NIHR Clinical Trials Research Network, Health and Care Research Wales, and AstraZeneca

KRAS Mutation Detection in Paired Frozen and Formalin-Fixed Paraffin-Embedded (FFPE) Colorectal Cancer Tissues

KRAS mutation has been unambiguously identified as a marker of resistance to cetuximab-based treatment in metastatic colorectal cancer (mCRC) patients. However, most studies of KRAS mutation analysis have been performed using homogenously archived CRC specimens, and studies that compare freshly frozen specimens and formalin-fixed paraffin-embedded (FFPE) specimens of CRC are lacking. The aim of the present study was to evaluate the impact of tissue preservation on the determination of KRAS mutational status. A series of 131 mCRC fresh-frozen tissues were first analyzed using both high-resolution melting (HRM) and direct sequencing. KRAS mutations were found in 47/131 (35.8%) using both approaches. Out of the 47 samples that were positive for KRAS mutations, 33 had available matched FFPE specimens. Using HRM, 2/33 (6%) demonstrated suboptimal template amplification, and 2/33 (6%) expressed an erroneous wild-type KRAS profile. Using direct sequencing, 6/33 (18.1%) displayed a wild-type KRAS status, and 3/33 (9.1%) showed discordant mutations. Finally, the detection of KRAS mutations was lower among the FFPE samples compared with the freshly frozen samples, demonstrating that tissue processing clearly impacts the accuracy of KRAS genotyping

Real-world comparison of the effects of etanercept and adalimumab on well-being in non-systemic juvenile idiopathic arthritis: a propensity score matched cohort study

Background: Etanercept (ETN) and adalimumab (ADA) are considered equally efective biologicals in the treat‑ ment of arthritis in juvenile idiopathic arthritis (JIA) but no studies have compared their impact on patient-reported well-being. The objective of this study was to determine whether ETN and ADA have a diferential efect on patientreported well-being in non-systemic JIA using real-world data. Methods: Biological-naive patients without a history of uveitis were selected from the international Pharmachild registry. Patients starting ETN were matched to patients starting ADA based on propensity score and outcomes were collected at time of therapy initiation and 3–12 months afterwards. Primary outcome at follow-up was the improve‑ ment in Juvenile Arthritis Multidimensional Assessment Report (JAMAR) visual analogue scale (VAS) well-being score from baseline. Secondary outcomes at follow-up were decrease in active joint count, adverse events and uveitis events. Outcomes were analyzed using linear and logistic mixed efects models. Results: Out of 158 eligible patients, 45 ETN starters and 45 ADA starters could be propensity score matched result‑ ing in similar VAS well-being scores at baseline. At follow-up, the median improvement in VAS well-being was 2 (inter‑ quartile range (IQR): 0.0 – 4.0) and scores were signifcantly better (P=0.01) for ETN starters (median 0.0, IQR: 0.0 – 1.0) compared to ADA starters (median 1.0, IQR: 0.0 – 3.5). The estimated mean diference in VAS well-being improvement from baseline for ETN versus ADA was 0.89 (95% CI: -0.01 – 1.78; P=0.06). The estimated mean diference in active joint count decrease was -0.36 (95% CI: -1.02 – 0.30; P=0.28) and odds ratio for adverse events was 0.48 (95% CI: 0.16 –1.44; P=0.19). One uveitis event was observed in the ETN group. Conclusions: Both ETN and ADA improve well-being in non-systemic JIA. Our data might indicate a trend towards a slightly stronger efect for ETN, but larger studies are needed to confrm this given the lack of statistical signifcance