High-Content Analysis of Breast Cancer Using Single-Cell Deep Transfer Learning

High-content analysis has revolutionized cancer drug discovery by identifying substances that alter the phenotype of a cell, which prevents tumor growth and metastasis. The high-resolution biofluorescence images from assays allow precise quantitative measures enabling the distinction of small molecules of a host cell from a tumor. In this work, we are particularly interested in the application of deep neural networks (DNNs), a cutting-edge machine learning method, to the classification of compounds in chemical mechanisms of action (MOAs). Compound classification has been performed using image-based profiling methods sometimes combined with feature reduction methods such as principal component analysis or factor analysis. In this article, we map the input features of each cell to a particular MOA class without using any treatment-level profiles or feature reduction methods. To the best of our knowledge, this is the first application of DNN in this domain, leveraging single-cell information. Furthermore, we use deep transfer learning (DTL) to alleviate the intensive and computational demanding effort of searching the huge parameter's space of a DNN. Results show that using this approach, we obtain a 30% speedup and a 2% accuracy improvement.

A Thematic Comparison of Eight Frameworks of Quality Criteria in Qualitative Health Research

Background: Despite the increasing incidences of the publication of assessment frameworks intending to establish the "standards" of the quality of qualitative research, the research conducted using such empirical methods are still facing difficulties in being published or recognised by funding agencies. Methods: We conducted a thematic content analysis of eight frameworks from psychology/psychiatry and general medicine. The frameworks and their criteria are then compared against each other. Findings: The results illustrated the difficulties in reaching consensus on the definition of quality criteria. This showed the differences between the frameworks from the point of views of the underlying epistemology and the criteria suggested. Discussion: The aforementioned differences reflect the diversity of paradigms implicitly referred to by the authors of the frameworks, although rarely explicitly mentioned in text. We conclude that the increase in qualitative research and publications has failed to overcome the difficulties in establishing shared criteria and the great heterogeneity of concepts raises methodological and epistemological problems.

The Patientʼs Perception of Eosinophilic Esophagitis Related Symptoms: a Qualitative Content Analysis

Background and Aims: The international EEsAI study group is currently developing an activity index for Eosinophilic Esophagitis (EoE). A potential discrepancy between patient and physician reported EoE symptoms has not been assessed yet. Therefore, we aimed to evaluate patient reported items describing their EoE activity and to compare these with the physicianʼs perception. Methods: A questionnaire was sent to 100 EoE patients in Switzerland. EoE-related symptoms dependent and independent of food intake were reported by patients. Results were analyzed using a qualitative content analysis and compared with symptoms reported by international EoE experts in Delphi rounds. Results: The questionnaire response rate was 64/100. The following items were developed by combining categories based on patients answers: food-consistency related dysphagia, frequency and severity of dysphagia, food impaction, strategies to avoid food impaction, food allergy, drinking-related retrosternal pain. The following food categories associated with dysphagia were identified: meat, rice, dry bread, French fries, raw, fibrous foods, others. Sports and psychological stress were identified as triggers for non-food intake related EoE symptoms. A good correlation was found between patient and physicianʼs reported EoE related symptoms. Conclusions: There is a good correlation between patient reported symptoms and the physicianʼs perception of clinical items as reported by international EoE experts. These patient reported outcomes will now be incorporated into the EEsAI questionnaire that measures EoE activity.

Qualitative analysis of barriers and facilitators encountered by HIV patients in an ART adherence programme.

Background Medication adherence is a complex, dynamic and changing behaviour that is affected by a variety of factors, including the patient's beliefs and life circumstances. Studies have highlighted barriers to medication adherence (e.g., unmanaged side effects or a lack of social support), as well as facilitators of medication adherence (e.g., technical simplicity of treatment and psychological acceptance of the disease). Since August 2004, in Lausanne (Switzerland), physicians have referred patients who are either experiencing or are at risk of experiencing problems with their HIV antiretroviral treatment (ART) to a routine interdisciplinary ART adherence programme. This programme consists of multifactorial intervention including electronic drug monitoring (MEMS(TM)). Objective This study's objective was to identify the barriers and facilitators encountered by HIV patients with suboptimal medication adherence (≤90 % adherence over the study period). Setting The community pharmacy of the Department of Ambulatory Care and Community Medicine in Lausanne (Switzerland). Method The study consisted of a retrospective, qualitative, thematic content analysis of pharmacists' notes that were taken during semi-structured interviews with patients and conducted as part of the ART adherence programme between August 2004 and May 2008. Main outcome measure Barriers and facilitators encountered by HIV patients. Results Barriers to and facilitators of adherence were identified for the 17 included patients. These factors fell into three main categories: (1) cognitive, emotional and motivational; (2) environmental, organisational and social; and (3) treatment and disease. Conclusion The pharmacists' notes revealed that diverse barriers and facilitators were discussed during medication adherence interviews. Indeed, the results showed that the 17 non-adherent patients encountered barriers and benefited from facilitators. Therefore, pharmacists should inquire about all factors, regardless of whether they have a negative or a positive impact on medication adherence, and should consider all dimensions of patient adherence. The simultaneous strengthening of facilitators and better management of barriers may allow healthcare providers to tailor care to a patient's specific needs and support each individual patient in improving his medication-related behaviour.

Inter-rater Reliability of Criteria-Based Content Analysis of Children's Statements of Abuse.

The evaluation of children's statements of sexual abuse cases in forensic cases is critically important and must and reliable. Criteria-based content analysis (CBCA) is the main component of the statement validity assessment (SVA), which is the most frequently used approach in this setting. This study investigated the inter-rater reliability (IRR) of CBCA in a forensic context. Three independent raters evaluated the transcripts of 95 statements of sexual abuse. IRR was calculated for each criterion, total score, and overall evaluation. The IRR was variable for the criteria, with several being unsatisfactory. But high IRR was found for the total CBCA scores (Kendall's W = 0.84) and for overall evaluation (Kendall's W = 0.65). Despite some shortcomings, SVA remains a robust method to be used in the comprehensive evaluation of children's statements of sexual abuse in the forensic setting. However, the low IRR of some CBCA criteria could justify some technical improvements.

Assessment of Young Learners’ English Proficiency in Bilingual Content Instruction CLIL

This applied linguistic study in the field of second language acquisition investigated the assessment practices of class teachers as well as the challenges and visions of language assessment in bilingual content instruction (CLIL) at primary level in Finnish basic education. Furthermore, pupils’ and their parents’ perceptions of language assessment and LangPerform computer simulations as an alternative, modern assessment method in CLIL contexts were examined. The study was conducted for descriptive and developmental purposes in three phases: 1) a CLIL assessment survey; 2) simulation 1; and 3) simulation 2. All phases had a varying number of participants. The population of this mixed methods study were CLIL class teachers, their pupils and the pupils’ parents. The sampling was multi-staged and based on probability and random sampling. The data were triangulated. Altogether 42 CLIL class teachers nationwide, 109 pupils from the 3rd, 4th and 5th grade as well as 99 parents from two research schools in South-Western Finland participated in the CLIL assessment survey followed by an audio-recorded theme interview of volunteers (10 teachers, 20 pupils and 7 parents). The simulation experimentations 1 and 2 produced 146 pupil and 39 parental questionnaires as well as video interviews of volunteered pupils. The data were analysed both quantitatively using percentages and numerical frequencies and qualitatively employing thematic content analysis. Based on the data, language assessment in primary CLIL is not an established practice. It largely appears to be infrequent, incidental, implicit and based on impressions rather than evidence or the curriculum. The most used assessment methods were teacher observation, bilingual tests and dialogic interaction, and the least used were portfolios, simulations and peer assessment. Although language assessment was generally perceived as important by teachers, a fifth of them did not gather assessment information systematically, and 38% scarcely gave linguistic feedback to pupils. Both pupils and parents wished to receive more information on CLIL language issues; 91% of pupils claimed to receive feedback rarely or occasionally, and 63% of them wished to get more information on their linguistic coping in CLIL subjects. Of the parents, 76% wished to receive more information on the English proficiency of their children and their linguistic development. This may be a response to indirect feedback practices identified in this study. There are several challenges related to assessment; the most notable is the lack of a CLIL curriculum, language objectives and common ground principles of assessment. Three diverse approaches to language in CLIL that appear to affect teachers’ views on language assessment were identified: instrumental (language as a tool), dual (language as a tool and object of learning) and eclectic (miscellaneous views, e.g. affective factors prioritised). LangPerform computer simulations seem to be perceived as an appropriate alternative assessment method in CLIL. It is strongly recommended that the fundamentals for assessment (curricula and language objectives) and a mutual assessment scheme should be determined and stakeholders’ knowledge base of CLIL strengthened. The principles of adequate assessment in primary CLIL are identified as well as several appropriate assessment methods suggested.

Socially Constructed Environmental Issues and Sport: A Content Analysis of Ski Resort Environmental Communications

Due to the impact of sport on the natural environment (UN, 2010), it is important to examine the interplay between environmental issues and sport (Hums, 2010, Mallen & Chard, 2011; Nauright & Pope, 2009; Ziegler, 2007). This research content analyzed 82 ski resort environmental communications (SRECs). These communications were rated for their prominence, breadth, and depth using the delineation of environmental issues provided by the Sustainable Slopes Program (SSP) Charter. This data was compared to the resorts’ degree of environmentally responsible action as rated by the Ski Area Citizens’ Coalition (SACC). An adaptation of Hudson and Miller's (2005) model was then used to classify the ski resorts as inactive, reactive, exploitive, or proactive in their environmental activities. Recommendations have been made for standardization and transparency in environmental disclosures and an environmental management system to aid ski resorts in moving from ad hoc processes to a systematic and comprehensive framework for improving environmental performance.

The Representation of the Feminine in the Portuguese Press : A Content Analysis of the Diário de Notícias Newspaper

This is a brief report of a research project, coordinated by me and funded by the Portuguese Government. It studies ‘The Representation of the Feminine in the Portuguese Press’ (POCI/COM 55780/2004), and works on the content analysis of discourse on the feminine in various Portuguese newspapers, covering the time span of February 1st till April 30th 2006. The paper is divided into two parts: in the first part, I will briefly discuss the typology used to code the text units of selected articles; in the second part, I will explore the most expressive percentages of the first two weeks of February for the content analysis of the Diário de Notícias newspaper. These percentages were obtained with the NVivo 6 qualitative data treatment software programme.

Sterol content analysis suggests altered eburicol 14 alpha-demethylase (CYP51) activity in isolates of Mycosphaerella graminicola adapted to azole fungicides

The recent decline in the effectiveness of some azole fungicides in controlling the wheat pathogen Mycosphaerella graminicola has been associated with mutations in the CYP51 gene encoding the azole target, the eburicol 14 alpha-demethylase (CYP51), an essential enzyme of the ergosterol biosynthesis pathway. In this study, analysis of the sterol content of M. graminicola isolates carrying different variants of the CYP51 gene has revealed quantitative differences in sterol intermediates, particularly the CYP51 substrate eburicol. Together with CYP51 gene expression studies, these data suggest that mutations in the CYP51 gene impact on the activity of the CYP51 protein.

Cloud information content analysis of multi-angular measurements in the oxygen A-band: application to 3MI and MSPI

The vertical distribution of cloud cover has a significant impact on a large number of meteorological and climatic processes. Cloud top altitude and cloud geometrical thickness are then essential. Previous studies established the possibility of retrieving those parameters from multi-angular oxygen A-band measurements. Here we perform a study and comparison of the performances of future instruments. The 3MI (Multi-angle, Multi-channel and Multi-polarization Imager) instrument developed by EUMETSAT, which is an extension of the POLDER/PARASOL instrument, and MSPI (Multi-angles Spectro-Polarimetric Imager) develoloped by NASA's Jet Propulsion Laboratory will measure total and polarized light reflected by the Earth's atmosphere–surface system in several spectral bands (from UV to SWIR) and several viewing geometries. Those instruments should provide opportunities to observe the links between the cloud structures and the anisotropy of the reflected solar radiation into space. Specific algorithms will need be developed in order to take advantage of the new capabilities of this instrument. However, prior to this effort, we need to understand, through a theoretical Shannon information content analysis, the limits and advantages of these new instruments for retrieving liquid and ice cloud properties, and especially, in this study, the amount of information coming from the A-Band channel on the cloud top altitude (CTOP) and geometrical thickness (CGT). We compare the information content of 3MI A-Band in two configurations and that of MSPI. Quantitative information content estimates show that the retrieval of CTOP with a high accuracy is possible in almost all cases investigated. The retrieval of CGT seems less easy but possible for optically thick clouds above a black surface, at least when CGT > 1–2 km.