Reliable detection of disseminated tumor cells and of the biodistribution of tumor-targeting therapeutic antibodies within the entire body has long been needed to better understand and treat cancer metastasis. Here, we developed an integrated pipeline for automated quantification of cancer metastases and therapeutic antibody targeting, named DeepMACT. First, we enhanced the fluorescent signal of cancer cells more than 100-fold by applying the vDISCO method to image metastasis in transparent mice. Second, we developed deep learning algorithms for automated quantification of metastases with an accuracy matching human expert manual annotation. Deep learning-based quantification in 5 different metastatic cancer models including breast, lung, and pancreatic cancer with distinct organotropisms allowed us to systematically analyze features such as size, shape, spatial distribution, and the degree to which metastases are targeted by a therapeutic monoclonal antibody in entire mice. DeepMACT can thus considerably improve the discovery of effective antibody-based therapeutics at the pre-clinical stage. VIDEO ABSTRACT.
The Working Group also thanks our Chairs, Dan Burnett, Matt Stone, Brent Zundel,and Wayne Chang, as well as our W3C Staff Contacts, Kazuyuki Ashimura andIvan Herman, for their expert management and steady guidance of the groupthrough the W3C standardization process.
Damas Expert 3 7 2 14
The first qualitative area of exploration from this exploratory sequential design is to identify the potential risks, in which the authors conduct in-depth interviews with ten different experts in Cambodia. Using the structural equation model (SEM) in AMOS and descriptive statistics analysis, this study investigates the risks that affect the RSC performance on an environmental, social and economic basis and subsequently proposes risk management strategies. The authors collect quantitative data from 200 Cambodian farmers through interviews and surveys.
This study applied diverse rules of thumb to establish the sample size of ten experts in Battambang province for the qualitative methodology to achieve saturation. The advantages of rules of thumb are quick and convenient.
The researchers employed an expert sampling method to choose each expert for in-depth interviews as part of a qualitative design. This sampling technique is significant because it is considered the best method to elicit the perspective of rice-farming specialists with a high level of knowledge and experience in a related field.
We used the index of consistency (IOC) to examine the construct validity and the consistency of the findings from the questionnaires. If the IOC score is found between 0.00 and 0.49, it is excluded from the questionnaire. But the question of items with more than 0.50 IOC score means validity, readability, clarity and comprehensiveness (Muangpan, 2015). We requested five experts who earned Ph.D. degrees and have experience of more than five years to determine the IOC score. The overall IOC score is 0.9.
More importantly, the researchers asked the experts to estimate the risk prioritization in their RSC. The risk prioritization relied on expected loss (expected loss scenarios = likelihood*effect). Figure 6 depicts these results.
She was previously the head of MENA corporate investigations atFTI Consulting where she managed many complex multi-jurisdictionalmatters in the field of integrity due diligence, asset tracing andlitigation support, including in Saudi Arabia, the UAE andLibya.Prior to her move into consulting, she was head of the MiddleEast and North Africa Country Risk Forecasting team at S&PGlobal, responsible for political risk forecasting, scenariomodelling and quantitative risk scoring across the whole region.Anna has led on projects including devising a political risk modelrelating to the security of Qatari food imports, managing a seriesof in-depth MENA region country studies for a US government client,and war-gaming possible future developments in the Syria conflict.She has provided expert comment to several media outlets includingAl Jazeera, Reuters and the BBC. Anna started her career as anArabic linguist with the Foreign and Commonwealth Office.Anna holds an MA with Distinction in Arabic from the School ofOriental and African Studies, having written her dissertation on1950s-60s Iraqi poetry. She also holds a 1st class honors degree inArabic from the University of Edinburgh and studied in Cairo andDamascus. She speaks French and Arabic.
This consensus must be based on data derived from all stakeholders involved in the care of individuals with OI including the people with OI themselves. In order to achieve this, an assembly of three groups from the OI community was formed, consisting of a lead team, an expert team and focus groups. In each country an ethical review was conducted and ethical approval was obtained where required.
The lead team consisted of six professionals, five were members of a pediatric or adult OI interdisciplinary team and the sixth was the coordinator from the non-government organization (NGO) Care4BrittleBones. The role of the lead team was to drive the overall project, spearhead the initial research and literature search, and prepare all materials for the video conferences, expert team meetings and focus groups. The expert team consisted of 21 professionals. Membership included internationally recognized professionals, as well as representatives of patient organizations from different countries. Overall, eight countries on three continents were represented. Clinical disciplines represented included orthopedic surgery, rehabilitation, genetics, pediatrics, psychology, physiotherapy, occupational therapy and endocrinology. The background of the professionals who participated is shown in Table 1. The role of the expert team was to advise and provide input on materials presented by the lead team, engage with others and work towards consensus by participating in Delphi rounds.
In order to reach consensus on every decision, modified Delphi rounds were held with the expert team. The lead team had no vote in the Delphi rounds. Over a period of one and a half years, the lead team together with the expert team held a total of 20 videoconferences. Also a final face to face meeting took place during an international conference in November 2019. Each meeting had at least 80% participation.
After reviewing the outcomes extracted from the literature, trials and registries, the lead team identified domains and the expert team proceeded to prioritize these domains. After three modified Delphi rounds, the expert team agreed on a final selection of these domains and their definition (ICF definition as well as a lay description). These domains were then presented to the focus groups after translation into the languages appropriate for the countries in which the focus groups were held.
The process for the focus groups was described in a detailed protocol including a standard set of slides and a scoring sheet to identify and prioritize the outcome domains taking into account the items of importance for the OI community and their wishes and hopes for the future per domain. Domains were ranked and then added or removed as per group consensus. The standardized approach was discussed at the outset with the national OI patient organizations in each country in order to respect the cultural aspects and to ensure that in each cultural setting the participants would feel comfortable to speak up in order to obtain outcomes of consistent quality. All content was collected and analyzed by the lead team and the final domains were determined by the expert team. Ethical review for the focus groups was obtained according to local requirements.
The literature search yielded over 6000 hits including 19 trials, 16 multicenter studies, and 2 registry studies. After correction for duplicates, 49 articles were reviewed and resulted in a database of 402 different outcome domains. After reducing the 402 domains reported in the literature to 44, these domains were then prioritized by the expert team through 3 modified Delphi rounds and 24 domains were selected (Table 2). These 24 domains with the ICF definition as well as a lay description were then presented to the focus groups. An overview of the process of selecting the outcome domains and measurements can be found in the flowchart in Fig. 2.
After four Delphi rounds the expert team reached consensus on the final set of measuring instruments shown in Table 3. For most domains, agreement was reached within the 1st and 2nd Delphi rounds. Some domains needed more discussion particularly those covered by patient reported outcomes measures (PROMs) covering multiple domains.
The expert team and focus groups expressed the need to address all aspects of bone fractures. Incidence, healing and type of treatment, as well as the mechanism of fracture (low impact vs high impact) in children will be reported. Incidence will be reported as the sum of clinically reported fractures, patient reported fractures and radiologically confirmed fractures, considering that not all fractures are always clearly visible on radiologic imaging. In daily practice, many patients are treated for clinical fractures without radiologic imaging or will manage minor fractures themselves without hospital visits and minimize the exposure to radiation.
The focus groups defined surgeries as major life events in the majority of cases, as the severity of the disease and the quality of healthcare was determined by the complexity and frequency of surgery and the outcome. The expert team decided to record these events.
The expert team agreed to include the measurement of scoliosis and kyphosis with Cobb angles on total spine X-rays as spinal deformities are common in OI and severe malformations of the spine may lead to various other problems affecting quality of life.
Given the frequency of malalignment, the relation between bowing and fractures, the possibility for guided growth, and the need for surgery to improve function if significant malalignment is present, the expert team chose long standing axis X-rays to measure and report on limb alignment. 2ff7e9595c
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