scholarly journals Utilisation of semiconductor sequencing for detection of actionable fusions in solid tumors

2021 ◽  
Author(s):  
Marco Loddo ◽  
Keeda-Marie Hardisty ◽  
Tiffany Haddow ◽  
Robert Thatcher ◽  
Gareth Williams
Keyword(s):  
Treatment Options ◽  
Real Life ◽  
Solid Tumours ◽  
Tissue Samples ◽  
Sequencing Platform ◽  
Cancer Management ◽  
Fda Approval ◽  
Semiconductor Sequencing ◽  
Wide Range ◽  
Personalised Treatment

Oncogenic  fusions represent compelling druggable targets in solid tumours highlighted by the recent site agnostic FDA approval of larotrectinib for NTRK rearrangements. However screening for fusions in routinely processed tissue samples is constrained due to degradation of nucleic acid as a result of formalin fixation., To investigate the clinical utility of semiconductor sequencing optimised for detection of actionable fusion transcripts in formalin fixed samples, we have undertaken  an analysis of test trending data  generated by a clinically validated next generation sequencing  platform designed to capture 867 of the most clinically relevant druggable driver-partner oncogenic fusions.   Here we showacross a real-life cohort of 1112 patients with solid tumours  that actionable fusions occur at high frequency (7.4%) with linkage to a wide range of targeted therapy protocols including seven fusion-drug matches with FDA/EMA approval and/or NCCN/ESMO recommendations and 80 clinical trials. The majority of actionable fusions identified were independent of tumour type in keeping with signalling via evolutionary conserved Wnt/β-catenin, RAS/RAF/MEK/ERK, PI3K/AKT/MTOR, PLCy/PKC and JAK/STAT pathways. Taken together our data indicates that semiconductor sequencing for detection of actionable fusions can be integrated into routine diagnostic pathology workflows enabling the identification of personalised treatment options that have potential to improve clinical cancer management across many tumour types.Oncogenic  fusions represent compelling druggable targets in solid tumours highlighted by the recent site agnostic FDA approval of larotrectinib for NTRK rearrangements. However screening for fusions in routinely processed tissue samples is constrained due to degradation of nucleic acid as a result of formalin fixation., To investigate the clinical utility of semiconductor sequencing optimised for detection of actionable fusion transcripts in formalin fixed samples, we have undertaken  an analysis of test trending data  generated by a clinically validated next generation sequencing  platform designed to capture 867 of the most clinically relevant druggable driver-partner oncogenic fusions.   Here we showacross a real-life cohort of 1112 patients with solid tumours  that actionable fusions occur at high frequency (7.4%) with linkage to a wide range of targeted therapy protocols including seven fusion-drug matches with FDA/EMA approval and/or NCCN/ESMO recommendations and 80 clinical trials. The majority of actionable fusions identified were independent of tumour type in keeping with signalling via evolutionary conserved Wnt/β-catenin, RAS/RAF/MEK/ERK, PI3K/AKT/MTOR, PLCy/PKC and JAK/STAT pathways. Taken together our data indicates that semiconductor sequencing for detection of actionable fusions can be integrated into routine diagnostic pathology workflows enabling the identification of personalised treatment options that have potential to improve clinical cancer management across many tumour types.

scholarly journals Treatment Comparison in Rheumatoid Arthritis: Head-to-Head Trials and Innovative Study Designs

2014 ◽  
Vol 2014 ◽  
pp. 1-17 ◽  
Author(s):  
Ennio Giulio Favalli ◽  
Serena Bugatti ◽  
Martina Biggioggero ◽  
Roberto Caporali
Keyword(s):  
Rheumatoid Arthritis ◽  
Treatment Options ◽  
Real Life ◽  
Treatment Comparison ◽  
Optimal Sequencing ◽  
Wide Range ◽  
Randomised Controlled ◽  
Meta Analyses ◽  
Study Designs ◽  
Indirect Comparisons

Over the last decades, the increasing knowledge in the area of rheumatoid arthritis has progressively expanded the arsenal of available drugs, especially with the introduction of novel targeted therapies such as biological disease modifying antirheumatic drugs (DMARDs). In this situation, rheumatologists are offered a wide range of treatment options, but on the other side the need for comparisons between available drugs becomes more and more crucial in order to better define the strategies for the choice and the optimal sequencing. Indirect comparisons or meta-analyses of data coming from different randomised controlled trials (RCTs) are not immune to conceptual and technical challenges and often provide inconsistent results. In this review we examine some of the possible evolutions of traditional RCTs, such as the inclusion of active comparators, aimed at individualising treatments in real-life conditions. Although head-to-head RCTs may be considered the best tool to directly compare the efficacy and safety of two different DMARDs, surprisingly only 20 studies with such design have been published in the last 25 years. Given the recent advent of the first RCTs truly comparing biological DMARDs, we also review the state of the art of head-to-head trials in RA.

Extraction of DNA from a Wide Range of Objects by Treatment with Ammonium Salts

2020 ◽  
Vol 36 (6) ◽  
pp. 98-106
Author(s):  
E.I. Levitin ◽  
B.V. Sviridov ◽  
O.V. Piksasova ◽  
T.E. Shustikova
Keyword(s):  
Dna Extraction ◽  
Dna Isolation ◽  
Tissue Samples ◽  
New Approach ◽  
Cell Wall Disruption ◽  
Wide Range ◽  
Low Salt ◽  
Mammalian Blood ◽  
Plasmid Extraction ◽  
Two Hybrid

Currently, simple, rapid, and efficient techniques for DNA isolation from a wide range of organisms are in demand in biotechnology and bioinformatics. A key (and often limiting) step is the cell wall disruption and subsequent DNA extraction from the disintegrated cells. We have developed a new approach to DNA isolation from organisms with robust cell walls. The protocol includes the following steps: treatment of cells or tissue samples with ammonium acetate followed by cell lysis in low-salt buffer with the addition of SDS. Further DNA extraction is carried out according to standard methods. This approach is efficient for high-molecular native DNA isolation from bacteria, ascomycetes, yeast, and mammalian blood; it is also useful for express analysis of environmental microbial isolates and for plasmid extraction for two-hybrid library screening. express method for DNA isolation; ammonium salt treatment (в русских ключевых такой порядок), osmotic breakage of cells This study was financially supported by the NRC "Kurchatov Institute"-GOSNIIGENETIKA Kurchatov Genomic Center.

Home Learning in Times of COVID: Experiences of Parents

2020 ◽  
Vol 7 (1) ◽  
pp. 9 ◽  
Author(s):  
Shelina Bhamani ◽  
Areeba Zainab Makhdoom ◽  
Vardah Bharuchi ◽  
Nasreen Ali ◽  
Sidra Kaleem ◽  
...  
Keyword(s):  
Real Life ◽  
Sampling Technique ◽  
Online Classes ◽  
Google Docs ◽  
Learning Gap ◽  
Wide Range ◽  
Home Learning ◽  
Collection Data ◽  
Learning At Home ◽  
At Home

<p align="center"><em>The widespread prevalence of COVID-19 pandemic has affected academia and parents alike. Due to the sudden closure of schools, students are missing social interaction which is vital for better learning and grooming while most schools have started online classes. This has become a tough routine for the parents working online at home since they have to ensure their children’s education. The study presented was designed to explore the experiences of home learning in times of COVID-19. A descriptive qualitative study was planned to explore the experiences of parents about home learning and management during COVID-19 to get an insight into real-life experiences.  Purposive sampling technique was used for data collection.  Data were collected from 19 parents falling in the inclusion criteria. Considering the lockdown problem, the data were collected via Google docs form with open-ended questions related to COVID-19 and home learning. Three major themes emerged after the data analysis: impact of COVID on children learning; support given by schools; and strategies used by caregivers at home to support learning. It was analyzed that the entire nation and academicians around the world have come forward to support learning at home offering a wide range of free online avenues to support parents to facilitate home-learning. Furthermore, parents too have adapted quickly to address the learning gap that have emerged in their children’s learning in these challenging times. Measures should be adopted to provide essential learning skills to children at home. Centralized data dashboards and educational technology may be used to keep the students, parents and schools updated.</em></p>

scholarly journals A Systematic Review and Qualitative Synthesis Resulting in a Typology of Elementary Classroom Movement Integration Interventions

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Spyridoula Vazou ◽  
Collin A. Webster ◽  
Gregory Stewart ◽  
Priscila Candal ◽  
Cate A. Egan ◽  
...  
Keyword(s):  
Physical Activity ◽  
Teacher Collaboration ◽  
A Priori ◽  
Real Life ◽  
Dose Intensity ◽  
Routine Practice ◽  
Qualitative Synthesis ◽  
Wide Range ◽  
Meta Analyses ◽  
Movement Integration

Abstract Background/Objective Movement integration (MI) involves infusing physical activity into normal classroom time. A wide range of MI interventions have succeeded in increasing children’s participation in physical activity. However, no previous research has attempted to unpack the various MI intervention approaches. Therefore, this study aimed to systematically review, qualitatively analyze, and develop a typology of MI interventions conducted in primary/elementary school settings. Subjects/Methods Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed to identify published MI interventions. Irrelevant records were removed first by title, then by abstract, and finally by full texts of articles, resulting in 72 studies being retained for qualitative analysis. A deductive approach, using previous MI research as an a priori analytic framework, alongside inductive techniques were used to analyze the data. Results Four types of MI interventions were identified and labeled based on their design: student-driven, teacher-driven, researcher-teacher collaboration, and researcher-driven. Each type was further refined based on the MI strategies (movement breaks, active lessons, other: opening activity, transitions, reward, awareness), the level of intrapersonal and institutional support (training, resources), and the delivery (dose, intensity, type, fidelity). Nearly half of the interventions were researcher-driven, which may undermine the sustainability of MI as a routine practice by teachers in schools. An imbalance is evident on the MI strategies, with transitions, opening and awareness activities, and rewards being limitedly studied. Delivery should be further examined with a strong focus on reporting fidelity. Conclusions There are distinct approaches that are most often employed to promote the use of MI and these approaches may often lack a minimum standard for reporting MI intervention details. This typology may be useful to effectively translate the evidence into practice in real-life settings to better understand and study MI interventions.

scholarly journals ECOCAPTURE@HOME: Protocol for the Remote Assessment of Apathy and Its Everyday-Life Consequences

2021 ◽  
Vol 18 (15) ◽  
pp. 7824
Author(s):  
Valérie Godefroy ◽  
Richard Levy ◽  
Arabella Bouzigues ◽  
Armelle Rametti-Lacroux ◽  
Raffaella Migliaccio ◽  
...  
Keyword(s):  
Everyday Life ◽  
New Technologies ◽  
Electrodermal Activity ◽  
Real Life ◽  
Smartphone Application ◽  
Measurement Model ◽  
Strong Impact ◽  
Active Data ◽  
Personalised Treatment

Apathy, a common neuropsychiatric symptom associated with dementia, has a strong impact on patients’ and caregivers’ quality of life. However, it is still poorly understood and hard to define. The main objective of the ECOCAPTURE programme is to define a behavioural signature of apathy using an ecological approach. Within this program, ECOCAPTURE@HOME is an observational study which aims to validate a method based on new technologies for the remote monitoring of apathy in real life. For this study, we plan to recruit 60 couples: 20 patient-caregiver dyads in which patients suffer from behavioral variant Fronto-Temporal Dementia, 20 patient-caregiver dyads in which patients suffer from Alzheimer Disease and 20 healthy control couples. These dyads will be followed for 28 consecutive days via multi-sensor bracelets collecting passive data (acceleration, electrodermal activity, blood volume pulse). Active data will also be collected by questionnaires on a smartphone application. Using a pool of metrics extracted from these passive and active data, we will validate a measurement model for three behavioural markers of apathy (i.e., daytime activity, quality of sleep, and emotional arousal). The final purpose is to facilitate the follow-up and precise diagnosis of apathy, towards a personalised treatment of this condition within everyday life.

scholarly journals Polymer-Drug Conjugates as Nanotheranostic Agents

2021 ◽  
Vol 2 (1) ◽  
pp. 63-81
Author(s):  
Sajana Manandhar ◽  
Erica Sjöholm ◽  
Johan Bobacka ◽  
Jessica M. Rosenholm ◽  
Kuldeep K. Bansal
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Treatment Options ◽  
The Body ◽  
Drug Conjugates ◽  
Imaging Characteristics ◽  
Wide Range ◽  
Systemic Side Effects ◽  
Theranostic Agents ◽  
The Stability

Since the last decade, the polymer-drug conjugate (PDC) approach has emerged as one of the most promising drug-delivery technologies owing to several benefits like circumventing premature drug release, offering controlled and targeted drug delivery, improving the stability, safety, and kinetics of conjugated drugs, and so forth. In recent years, PDC technology has advanced with the objective to further enhance the treatment outcomes by integrating nanotechnology and multifunctional characteristics into these systems. One such development is the ability of PDCs to act as theranostic agents, permitting simultaneous diagnosis and treatment options. Theranostic nanocarriers offer the opportunity to track the distribution of PDCs within the body and help to localize the diseased site. This characteristic is of particular interest, especially among those therapeutic approaches where external stimuli are supposed to be applied for abrupt drug release at the target site for localized delivery to avoid systemic side effects (e.g., Visudyne®). Thus, with the help of this review article, we are presenting the most recent updates in the domain of PDCs as nanotheranostic agents. Different methodologies utilized to design PDCs along with imaging characteristics and their applicability in a wide range of diseases, have been summarized in this article.

scholarly journals The Supportive Care Needs of Cancer Patients: a Systematic Review

2021 ◽  
Author(s):  
Madeleine Evans Webb ◽  
Elizabeth Murray ◽  
Zane William Younger ◽  
Henry Goodfellow ◽  
Jamie Ross
Keyword(s):  
Cancer Patients ◽  
Healthcare Professionals ◽  
Treatment Options ◽  
Complex Nature ◽  
Narrative Synthesis ◽  
Care Needs ◽  
Wide Range ◽  
Need Support ◽  
Lack Of Control ◽  
Everyday Work

AbstractCancer, and the complex nature of treatment, has a profound impact on lives of patients and their families. Subsequently, cancer patients have a wide range of needs. This study aims to identify and synthesise cancer patients’ views about areas where they need support throughout their care. A systematic  search of the literature from PsycInfo, Embase and Medline databases was conducted, and a narrative. Synthesis of results was carried out using the Corbin & Strauss “3 lines of work” framework. For each line of work, a group of key common needs were identified. For illness-work, the key needs idenitified were; understanding their illness and treatment options, knowing what to expect, communication with healthcare professionals, and staying well. In regards to everyday work, patients wanted to maintain a sense of normalcy and look after their loved ones. For biographical work, patients commonly struggled with the emotion impact of illness and a lack of control over their lives. Spiritual, sexual and financial problems were less universal. For some types of support, demographic factors influenced the level of need reported. While all patients are unique, there are a clear set of issues that are common to a majority of cancer journeys. To improve care, these needs should be prioritised by healthcare practitioners.

scholarly journals Estimating the number of usability problems affecting medical devices: modelling the discovery matrix

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Vincent Vandewalle ◽  
Alexandre Caron ◽  
Coralie Delettrez ◽  
Renaud Périchon ◽  
Sylvia Pelayo ◽  
...  
Keyword(s):  
Medical Devices ◽  
Market Access ◽  
Real Life ◽  
Usability Testing ◽  
Probability Of Detection ◽  
Usability Problems ◽  
Usability Problem ◽  
Wide Range ◽  
The Matrix ◽  
Problem Detection

Abstract Background Usability testing of medical devices are mandatory for market access. The testings’ goal is to identify usability problems that could cause harm to the user or limit the device’s effectiveness. In practice, human factor engineers study participants under actual conditions of use and list the problems encountered. This results in a binary discovery matrix in which each row corresponds to a participant, and each column corresponds to a usability problem. One of the main challenges in usability testing is estimating the total number of problems, in order to assess the completeness of the discovery process. Today’s margin-based methods fit the column sums to a binomial model of problem detection. However, the discovery matrix actually observed is truncated because of undiscovered problems, which corresponds to fitting the marginal sums without the zeros. Margin-based methods fail to overcome the bias related to truncation of the matrix. The objective of the present study was to develop and test a matrix-based method for estimating the total number of usability problems. Methods The matrix-based model was based on the full discovery matrix (including unobserved columns) and not solely on a summary of the data (e.g. the margins). This model also circumvents a drawback of margin-based methods by simultaneously estimating the model’s parameters and the total number of problems. Furthermore, the matrix-based method takes account of a heterogeneous probability of detection, which reflects a real-life setting. As suggested in the usability literature, we assumed that the probability of detection had a logit-normal distribution. Results We assessed the matrix-based method’s performance in a range of settings reflecting real-life usability testing and with heterogeneous probabilities of problem detection. In our simulations, the matrix-based method improved the estimation of the number of problems (in terms of bias, consistency, and coverage probability) in a wide range of settings. We also applied our method to five real datasets from usability testing. Conclusions Estimation models (and particularly matrix-based models) are of value in estimating and monitoring the detection process during usability testing. Matrix-based models have a solid mathematical grounding and, with a view to facilitating the decision-making process for both regulators and device manufacturers, should be incorporated into current standards.

scholarly journals An Interoperability Platform Enabling Reuse of Electronic Health Records for Signal Verification Studies

2016 ◽  
Vol 2016 ◽  
pp. 1-18 ◽  
Author(s):  
Mustafa Yuksel ◽  
Suat Gonul ◽  
Gokce Banu Laleci Erturkmen ◽  
Ali Anil Sinaci ◽  
Paolo Invernizzi ◽  
...  
Keyword(s):  
Real Life ◽  
Case Series ◽  
Background Information ◽  
Data Sets ◽  
Local Data ◽  
Lombardy Region ◽  
Common Information ◽  
Spontaneous Reports ◽  
Wide Range ◽  
Common Information Model

Depending mostly on voluntarily sent spontaneous reports, pharmacovigilance studies are hampered by low quantity and quality of patient data. Our objective is to improve postmarket safety studies by enabling safety analysts to seamlessly access a wide range of EHR sources for collecting deidentified medical data sets of selected patient populations and tracing the reported incidents back to original EHRs. We have developed an ontological framework where EHR sources and target clinical research systems can continue using their own local data models, interfaces, and terminology systems, while structural interoperability and Semantic Interoperability are handled through rule-based reasoning on formal representations of different models and terminology systems maintained in the SALUS Semantic Resource Set. SALUS Common Information Model at the core of this set acts as the common mediator. We demonstrate the capabilities of our framework through one of the SALUS safety analysis tools, namely, the Case Series Characterization Tool, which have been deployed on top of regional EHR Data Warehouse of the Lombardy Region containing about 1 billion records from 16 million patients and validated by several pharmacovigilance researchers with real-life cases. The results confirm significant improvements in signal detection and evaluation compared to traditional methods with the missing background information.

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