Search results for: mike hat

Authors: Mike Wei, Nebu Koshy, Koen van Besien, Giorgio Inghirami, Steven M. Horwitz

Abstract:

T-cell prolymphocytic leukemia (T-PLL) is a rare hematologic disease characterized by a T-cell phenotype, rapid progression, and poor prognosis with median survival of less than a year. Alemtuzumab-based chemotherapy has increased the rate of complete remissions but these are often short-lived, and allogeneic transplant is considered the only curative therapy. In recent studies, JAK3 activating mutations have been identified in T-cell cancers, with T-PLL having the highest rate of JAK3 mutations (30 – 42%). As such, T-PLL is a model disease for evaluating the utility of JAK3 inhibitors. We present a case of a 64-year-old man with relapsed-refractory T-PLL. He was initially treated with alemtuzumab and obtained complete response and was consolidated with matched unrelated donor stem cell transplant. His disease stayed in remission for approximately 1.5 years before relapse, which was then treated with a clinical trial of romidepsin-lenalidomide (partial responses then progression at 6 months) and later alemtuzumab. Due to complications of myelosuppression and CMV reactivation, his treatment was interrupted leading to disease progression. The doubling time of lymphocyte count was approximately 20 days and over a span of 60 days the lymphocyte count rose from 8 x 109/L to 68 x 109/L. Exon sequencing showed a JAK3 mutation. The patient consented to and was treated with FDA-approved tofacitinib (initially 5 mg BID, increased to 10 mg BID after 15 days of treatment). An initial decrease in lymphocyte count was followed by progression. In vitro treatment of the patient’s cells showed modest effects of tofacitinib and ruxolitinib as single agents, in the range of doxorubicin, but synergy between the agents. After 40 days of treatment with tofacitinib and with a lymphocyte count of 150 x 109/L, ruxolitinib (5mg BID) was added. Over the 60 days since dual inhibition was started, the lymphocyte count has stabilized. The patient has remained completely asymptomatic during treatment with tofacitinib and ruxolitinib. Neutrophil count has remained normal. Platelet count and hemoglobin have however declined from ~50 x109/L to ~30 x109/L and from 11 g/dL to 8.1 g/dL respectively, since the introduction of ruxolitinib. The stabilization in lymphocyte count confirms the clinical activity of JAK inhibitors in T-PLL as suggested by the presence of JAK3 mutations and by in-vitro assays. It also suggests clinical synergy between ruxolitinib and tofacitinib in this setting. Prospective studies of JAK inhibitors in PLL patients with formal dose-finding studies are needed.

Keywords: tofacitinib, ruxolitinib, T-cell prolymphocytic leukemia, JAK3

Procedia PDF Downloads 311

Authors: Mike Wei, Mario Cedillo, Jiahui Lin, Carol Lorraine Storey-Johnson, Carla Boutin-Foster

Abstract:

Purpose: The extent to which health insurance enrollment succeeds under the Affordable Care Act (ACA) rests heavily on the ability to reach the uninsured and motivate them to enroll. We sought to identify perceptions about the ACA among uninsured patients at a free clinic in New York City. Background: The ACA holds tremendous promise for reducing the number of uninsured Americans. As of April 2014, nearly 8 million people had signed up for health insurance through the Health Insurance Marketplace. Despite this early success, future and continued enrollment rests heavily on the degree of public awareness. Reaching eligible individuals and increasing their awareness and understanding remains a fundamental challenge to realizing the full potential of the ACA. Reaching out to uninsured patients who are seeking care through safety net facilities such as free clinics may provide important avenues for reaching potential enrollees. This project focuses on the experience at the free clinic at Weill Cornell Medical College, the Weill Cornell Community Clinic (WCCC), and seeks to understand perceptions about the ACA among its patient population. Methods: This was a cross-sectional study of all patients who visited the free clinic at Weill Cornell Medical College, the Weill Cornell Community Clinic, from July 2013 to May 2014. Patients who provided informed consent at their visit and completed a semi-structured questionnaire were included (N=62). The questionnaire comprised of questions about demographic characteristics and open-ended questions about their knowledge and perception of the impact of the ACA. Descriptive statistics were used to characterize the population demographics. Qualitative coding techniques were used for open-ended items. Results: Approximately one third of patients surveyed never had health insurance. Of the remaining 65%, 20% lost their insurance within the past year. Only 55% had heard about the ACA, and only 10% knew about the Health Benefits Exchange. Of those who had heard about the ACA, sentiments were tinged with optimistic misperceptions, such as “it will be free health care for all.” While optimistic, most of the responses focused on the economic implications of the ACA. Conclusions: These findings reveal the immense amount of misconception and lack of understanding with regards to the ACA. As such, the study highlights the need to educate and address the concerns of those who remain skeptical or uncertain about the implications of the ACA.

Keywords: Affordable Care Act, demographics, free clinics, underserved.

Procedia PDF Downloads 390

Authors: S. Chowdhury, A. Corlett

Abstract:

Large tsunamis strike the British Columbia coast every few hundred years. The Cascadia Subduction Zone, which extends along the Pacific coast from Vancouver Island to Northern California is one of the most seismically active regions in Canada. Significant earthquakes have occurred in this region, including the 1700 Cascade Earthquake with an estimated magnitude of 9.2. Based on geological records, experts have predicted a 'great earthquake' of a similar magnitude within this region may happen any time. This earthquake is expected to generate a large tsunami that could impact the coastal communities on Vancouver Island. Since many of these communities are in remote locations, they are more likely to be vulnerable, as the post-earthquake relief efforts would be impacted by the damage to critical road infrastructures. To assess the coastal vulnerability within these communities, a hydrodynamic model has been developed using MIKE-21 software. We have considered a 500 year probabilistic earthquake design criteria including the subsidence in this model. The bathymetry information was collected from Canadian Hydrographic Services (CHS), and National Oceanic Atmospheric and Administration (NOAA). The arial survey was conducted using a Cessna-172 aircraft for the communities, and then the information was converted to generate a topographic digital elevation map. Both survey information was incorporated into the model, and the domain size of the model was about 1000km x 1300km. This model was calibrated with the tsunami occurred off the west coast of Moresby Island on October 28, 2012. The water levels from the model were compared with two tide gauge stations close to the Vancouver Island and the output from the model indicates the satisfactory result. For this study, the design water level was considered as High Water Level plus the Sea Level Rise for 2100 year. The hourly wind speeds from eight directions were collected from different wind stations and used a 200-year return period wind speed in the model for storm events. The regional model was set for 12 hrs simulation period, which takes more than 16 hrs to complete one simulation using double Xeon-E7 CPU computer plus a K-80 GPU. The boundary information for the local model was generated from the regional model. The local model was developed using a high resolution mesh to estimate the coastal flooding for the communities. It was observed from this study that many communities will be effected by the Cascadia tsunami and the inundation maps were developed for the communities. The infrastructures inside the coastal inundation area were identified. Coastal vulnerability planning and resilient design solutions will be implemented to significantly reduce the risk.

Keywords: tsunami, coastal flooding, coastal vulnerable, earthquake, Vancouver, wave propagation

Procedia PDF Downloads 132

Authors: Akmez Nabeerasool, Michaelis Massaros, Nigel Brown, David Sanderson, David Parocki, Charlotte Thompson, Mike Lodge, Mikael Khan

Abstract:

The provision of clean and safe drinking water is of paramount importance and is a basic human need. Water scarcity coupled with tightening of regulations and the inability of current treatment technologies to deal with emerging contaminants and Pharmaceuticals and personal care products means that alternative treatment technologies that are viable and cost effective are required in order to meet demand and regulations for clean water supplies. Logistically, the application of water treatment in rural areas presents unique challenges due to the decentralisation of abstraction points arising from low population density and the resultant lack of infrastructure as well as the need to treat water at the site of use. This makes it costly to centralise treatment facilities and hence provide potable water direct to the consumer. Furthermore, across the UK there are segments of the population that rely on a private water supply which means that the owner or user(s) of these supplies, which can serve one household to hundreds, are responsible for the maintenance. The treatment of these private water supply falls on the private owners, and it is imperative that a chemical free technological solution that can operate unattended and does not produce any waste is employed. Arvia’s patented advanced oxidation technology combines the advantages of adsorption and electrochemical regeneration within a single unit; the Organics Destruction Cell (ODC). The ODC uniquely uses a combination of adsorption and electrochemical regeneration to destroy organics. Key to this innovative process is an alternative approach to adsorption. The conventional approach is to use high capacity adsorbents (e.g. activated carbons with high porosities and surface areas) that are excellent adsorbents, but require complex and costly regeneration. Arvia’s technology uses a patent protected adsorbent, Nyex™, which is a non-porous, highly conductive, graphite based adsorbent material that enables it to act as both the adsorbent and as a 3D electrode. Adsorbed organics are oxidised and the surface of the Nyex™ is regenerated in-situ for further adsorption without interruption or replacement. Treated water flows from the bottom of the cell where it can either be re-used or safely discharged. Arvia™ Technology Ltd. has trialled the application of its tertiary water treatment technology in treating reservoir water abstracted near Glasgow, Scotland, with promising results. Several other pilot plants have also been successfully deployed at various locations in the UK showing the suitability and effectiveness of the technology in removing recalcitrant organics (including pharmaceuticals, steroids and hormones), COD and colour.

Keywords: Arvia™ process, adsorption, water treatment, electrochemical oxidation

Procedia PDF Downloads 264

Authors: Dalal Albudaiwi, Mike Allen, Talal Alhaji, Shahnaz Khadimehzadah

Abstract:

As a pandemic, COVID-19 has impacted the whole world since November 2019. In other words, every organization, industry, and institution has been negatively affected by the Coronavirus. The uncertainty of how long the pandemic will last caused chaos at all levels. As with any other institution, public libraries were affected and transmitted into online services and resources. As internationally, have been witnessed that some public libraries were well-prepared for such disasters as the pandemic, and therefore, collections, users, services, technologies, staff, and budgets were all influenced. Public libraries’ policies did not mention any plan regarding such a pandemic. Instead, there are several rules in the guidelines about disasters in general, such as natural disasters. In this pandemic situation, libraries have been involved in different uneasy circumstances. However, it has always been apparent to public libraries the role they play in serving their communities in excellent and critical times. It dwells into the traditional role public libraries play in providing information services and sources to satisfy their information-based community needs. Remarkably increasing people’s awareness of the importance of informational enrichment and enhancing society’s skills in dealing with information and information sources. Under critical circumstances, libraries play a different role. It goes beyond the traditional part of information providers to the untraditional role of being a social institution that serves the community with whatever capabilities they have. This study takes two significant directions. The first focuses on investigating how libraries have responded to COVID-19 and how they manage disasters within their organization. The second direction focuses on how libraries help their communities to act during disasters and how to recover from the consequences. The current study examines how libraries prepare for disasters and the role of public libraries during disasters. We will also propose “measures” to be a model that libraries can use to evaluate the effectiveness of their response to disasters. We intend to focus on how libraries responded to this new disaster. Therefore, this study aims to develop a comprehensive policy that includes responding to a crisis such as Covid-19. An analytical lens inside the libraries as an organization and outside the organization walls will be documented based on analyzing disaster-related literature published in the LIS publication. The study employs content analysis (CA) methodology. CA is widely used in the library and information science. The critical contribution of this work is to propose solutions it provides to libraries and planers to prepare crisis management plans/ policies, specifically to face a new global disaster such as the COVID-19 pandemic. Moreover, the study will help library directors to evaluate their strategies and to improve them properly. The significance of this study lies in guiding libraries’ directors to enhance the goals of the libraries to guarantee crucial issues such as: saving time, avoiding loss, saving budget, acting quickly during a crisis, maintaining libraries’ role during pandemics, finding out the best response to disasters, and creating plan/policy as a sample for all libraries.

Keywords: Covid-19, policy, preparedness, public libraries

Procedia PDF Downloads 83

Authors: Michal Lysek, Mike Danilovic, Jasmine Lihua Liu

Abstract:

HMS Industrial Networks AB has been recognized as one of the most innovative companies in the industrial communication industry worldwide. The creation of their Anybus innovation during the 1990s contributed considerably to the company’s success. From inception, HMS’ employees were innovating for the purpose of creating new business (the creation phase). After the Anybus innovation, they began the process of internationalization (the commercialization phase), which in turn led them to concentrate on cost reduction, product quality, delivery precision, operational efficiency, and increasing growth (the growth phase). As a result of this transformation, performing new radical innovations have become more complicated. The purpose of our research was to explore the dynamics of innovation at HMS from the aspect of key actors, activities, and events, over the three phases, in order to understand what led to the creation of their Anybus innovation, and why it has become increasingly challenging for HMS to create new radical innovations for the future. Our research methodology was based on a longitudinal, retrospective study from the inception of HMS in 1988 to 2014, a single case study inspired by the grounded theory approach. We conducted 47 interviews and collected 1 024 historical documents for our research. Our analysis has revealed that HMS’ success in creating the Anybus, and developing a successful business around the innovation, was based on three main capabilities – cultivating customer relations on different managerial and organizational levels, inspiring business relations, and balancing complementary human assets for the purpose of business creation. The success of HMS has turned the management’s attention away from past activities of key actors, of their behavior, and how they influenced and stimulated the creation of radical innovations. Nowadays, they are rhetorically focusing on creativity and innovation. All the while, their real actions put emphasis on growth, cost reduction, product quality, delivery precision, operational efficiency, and moneymaking. In the process of becoming an international company, HMS gradually refocused. In so doing they became profitable and successful, but they also forgot what made them innovative in the first place. Fortunately, HMS’ management has come to realize that this is the case and they are now in search of recapturing innovation once again. Our analysis indicates that HMS’ management is facing several barriers to innovation related path dependency and other lock-in phenomena. HMS’ management has been captured, trapped in their mindset and actions, by the success of the past. But now their future has to be secured, and they have come to realize that moneymaking is not everything. In recent years, HMS’ management have begun to search for innovation once more, in order to recapture their past capabilities for creating radical innovations. In order to unlock their managerial perceptions of customer needs and their counter-innovation driven activities and events, to utilize the full potential of their employees and capture the innovation opportunity for the future.

Keywords: barriers to innovation, dynamics of innovation, in search of excellence and innovation, radical innovation

Procedia PDF Downloads 380

Authors: Aikaterini Tavoulari, Mike Richardson

Abstract:

Objective: This abstract presents a multisensory participatory design project, inspired by a deafblind PhD student's ambition to climb Mount Everest. The project aims to explore accessible routes for filmmaking and video content creation, catering to the needs of individuals with hearing and sight loss. By engaging participants from the Southwest area of England, recruited through multiple networks, the project seeks to gather qualitative data and insights to inform the development of inclusive media practices. Design: It will be a community-based participatory research design. The workshop will feature various stations that stimulate different senses, such as scent, touch, sight, hearing as well as movement. Participants will have the opportunity to engage with these multisensory experiences, providing valuable feedback on their effectiveness and potential for enhancing accessibility in filmmaking and video content. Methods: Brief semi-structured interviews will be conducted to collect qualitative data, allowing participants to share their perspectives, challenges, and suggestions for improvement. The participatory design approach emphasizes the importance of involving the target audience in the creative process. By actively engaging individuals with hearing and sight loss, the project aims to ensure that their needs and preferences are central to the development of accessible filmmaking techniques and video content. This collaborative effort seeks to bridge the gap between content creators and diverse audiences, fostering a more inclusive media landscape. Results: The findings from this study will contribute to the growing body of research on accessible filmmaking and video content creation. Via inductive thematic analysis of the qualitative data collected through interviews and observations, the researchers aim to identify key themes, challenges, and opportunities for creating engaging and inclusive media experiences for deafblind audiences. The insights will inform the development of best practices and guidelines for accessible filmmaking, empowering content creators to produce more inclusive and immersive video content. Conclusion: The abstract targets the hybrid International Conference for Disability and Diversity in Canada (January 2025), as this platform provides an excellent opportunity to share the outcomes of the project with a global audience of researchers, practitioners, and advocates working towards inclusivity and accessibility in various disability domains. By presenting this research at the conference in person, the authors aim to contribute to the ongoing discourse on disability and diversity, highlighting the importance of multisensory experiences and participatory design in creating accessible media content for the deafblind community and the community with sensory impairments more broadly.

Keywords: vision impairment, hearing impairment, deafblindness, accessibility, filmmaking

Procedia PDF Downloads 45

Authors: Yazan S. Khaled, Shazana Shamsuddin, Jim Tiernan, Mike McPherson, Thomas Hughes, Paul Millner, David G. Jayne

Abstract:

Introduction: There is a need for real-time imaging of colorectal cancer (CRC) to allow tailored surgery to the disease stage. Fluorescence guided laparoscopic imaging of primary colorectal cancer and the draining lymphatics would potentially bring stratified surgery into clinical practice and realign future CRC management to the needs of patients. Fluorescent nanoparticles can offer many advantages in terms of intra-operative imaging and therapy (theranostic) in comparison with traditional soluble reagents. Nanoparticles can be functionalised with diverse reagents and then targeted to the correct tissue using an antibody or Affimer (artificial binding protein). We aimed to develop and test fluorescent silica nanoparticles and targeted against CRC using an anti-carcinoembryonic antigen (CEA) Affimer (Aff). Methods: Anti-CEA and control Myoglobin Affimer binders were subcloned into the expressing vector pET11 followed by transformation into BL21 Star™ (DE3) E.coli. The expression of Affimer binders was induced using 0.1 mM isopropyl β-D-1-thiogalactopyranoside (IPTG). Cells were harvested, lysed and purified using nickle chelating affinity chromatography. The photosensitiser Foslip (soluble analogue of 5,10,15,20-Tetra(m-hydroxyphenyl) chlorin) was incorporated into the core of silica nanoparticles using water-in-oil microemulsion technique. Anti-CEA or control Affs were conjugated to silica nanoparticles surface using sulfosuccinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate (sulfo SMCC) chemical linker. Binding of CEA-Aff or control nanoparticles to colorectal cancer cells (LoVo, LS174T and HC116) was quantified in vitro using confocal microscopy. Results: The molecular weights of the obtained band of Affimers were ~12.5KDa while the diameter of functionalised silica nanoparticles was ~80nm. CEA-Affimer targeted nanoparticles demonstrated 9.4, 5.8 and 2.5 fold greater fluorescence than control in, LoVo, LS174T and HCT116 cells respectively (p < 0.002) for the single slice analysis. A similar pattern of successful CEA-targeted fluorescence was observed in the maximum image projection analysis, with CEA-targeted nanoparticles demonstrating 4.1, 2.9 and 2.4 fold greater fluorescence than control particles in LoVo, LS174T, and HCT116 cells respectively (p < 0.0002). There was no significant difference in fluorescence for CEA-Affimer vs. CEA-Antibody targeted nanoparticles. Conclusion: We are the first to demonstrate that Foslip-doped silica nanoparticles conjugated to anti-CEA Affimers via SMCC allowed tumour cell-specific fluorescent targeting in vitro, and had shown sufficient promise to justify testing in an animal model of colorectal cancer. CEA-Affimer appears to be a suitable targeting molecule to replace CEA-Antibody. Targeted silica nanoparticles loaded with Foslip photosensitiser is now being optimised to drive photodynamic killing, via reactive oxygen generation.

Keywords: colorectal cancer, silica nanoparticles, Affimers, antibodies, imaging

Procedia PDF Downloads 240

Authors: Peter Heimerl, Alexander Plaikner, Mike Peters

Abstract:

Background and Significance of the Study: Family-run businesses are a decisive economic factor in the Alpine tourism and leisure industry. Within the next years, it is expected that a large number of family-run small and medium-sized businesses will transfer ownership due to demographic developments. Four stages of succession processes can be identified by several empirical studies: (1) the preparation phase, (2) the succession planning phase, (3) the development of the succession concept, (4) and the implementation of the business transfer. Family business research underlines the importance of individual's and family’s values: Especially leadership values address mainly the first phase, which strongly determines the following stages. Aim of the Study: The study aims at answering the following research question: Which leadership values are dominating during succession processes in family-run businesses in Austrian Alpine tourism industry? Methodology: Twenty-two problem-centred individual interviews with 11 transferors and their 11 transferees were conducted. Data analysis was carried out using the software program MAXQDA following an inductive approach to data coding. Major Findings: Data analysis shows that nine values particularly influence succession processes, especially during the vulnerable preparation phase. Participation is the most-dominant value (162 references). It covers a style of cooperation, communication, and controlling. Discipline (142) is especially prevailing from the transferor's perspective. It addresses entrepreneurial honesty and customer orientation. Development (138) is seen as an important value, but it can be distinguished between transferors and transferees. These are mainly focused on strategic positioning and new technologies. Trust (105) is interpreted as a basic prerequisite to run the family firm smoothly. Interviewees underline the importance to be able to take a break from family-business management; however, this is only possible when openness and honesty constitute trust within the family firm. Loyalty (102): Almost all interviewees perceive that they can influence the loyalty of the employees through their own role models. A good work-life balance (90) is very important to most of the transferors, especially for their employees. Despite the communicated importance of a good work-life-balance, but however, mostly the commitment to the company is prioritised. Considerations of regionality (82) and regional responsibility are also frequently raised. Appreciation (75) is of great importance to both the handover and the takeover generation -as appreciation towards the employees in the company and especially in connection with the family. Familiarity (66) and the blurring of the boundaries between private and professional life are very common, especially in family businesses. Familial contact and open communication with employees which is mentioned in almost all handing over. Conclusions: In the preparation phase of succession, successors and incumbents have to consider and discuss their leadership and family values of family-business management. Quite often, assistance is needed to commonly and openly discuss these values in the early stages of succession processes. A large majority of handovers fail because of these values. Implications can be drawn to support family businesses, e.g., consulting initiatives at chambers of commerce and business consultancies must address this problem.

Keywords: leadership values, family business, succession processes, succession phases

Procedia PDF Downloads 99

Authors: Jessica Terese Mueller, Christoph Breitsprecher, Mike Oliver Mosko

Abstract:

Due to an unusually high number of asylum seekers entering Germany over the course of the past few years, the need for community interpreters has increased dramatically, in order to make the communication between asylum seekers and various actors in social and governmental agencies possible. In the field of social work in particular, there are community interpreters who possess a wide spectrum of qualifications spanning from state-certified professional interpreters with graduate degrees to lay or ad-hoc interpreters with little to no formal training. To the best of our knowledge, Germany has no official national quality standards for the training of community interpreters at present, which would serve to professionalise this field as well as to assure a certain degree of quality in the training programmes offered. Given the current demand for trained community interpreters, there is a growing number of training programmes geared toward qualifying community interpreters who work with asylum seekers in Germany. These training programmes range from short one-day workshops to graduate programmes with specialisations in Community Interpreting. As part of a larger project to develop quality standards for the qualification of community interpreters working with asylum seekers in the field of social work, a needs assessment was performed in the city-state of Hamburg and the state of North Rhine Westphalia in the form of focus groups and individual interviews with relevant actors in the field in order to determine the content and practical knowledge needed for community interpreters from the perspectives of those who work in and rely on this field. More specifically, social workers, volunteers, certified language and cultural mediators, paid and volunteer community interpreters and asylum seekers were invited to take part in focus groups in both locations, and asylum seekers, training providers, researchers, linguists and other national and international experts were individually interviewed. The responses collected in these focus groups and interviews have been analysed using Mayring’s concept of content analysis. In general, the responses indicate a high degree of overlap related to certain categories as well as some categories which seemed to be of particular importance to certain groups individually, while showing little to no relevance for other groups. For example, the topics of accuracy and transparency of the interpretations, as well as professionalism and ethical concerns were touched on in some form in most groups. Some group-specific topics which are the focus of experts were topics related to interpreting techniques and more concretely described theoretical and practical knowledge which should be covered in training programmes. Social workers and volunteers generally concentrated on issues regarding the role of the community interpreters and the importance of setting and clarifying professional boundaries. From the perspective of service receivers, asylum seekers tended to focus on the importance of having access to interpreters who are from their home region or country and who speak the same regiolect, dialect or variety as they do in order to prevent misunderstandings or misinterpretations which might negatively affect their asylum status. These results indicate a certain degree of consensus with trainings offered internationally for community interpreters.

Keywords: asylum seekers, community interpreting, needs assessment, quality standards, training

Procedia PDF Downloads 167

Authors: Jing Zhang, Yvonne Reinwald, Nick Poulson, Alicia El Haj, Chung See, Mike Somekh, Melissa Mather

Abstract:

Biomedical imaging of native tissue using light offers the potential to obtain excellent structural and functional information in a non-invasive manner with good temporal resolution. Image contrast can be derived from intrinsic absorption, fluorescence, or scatter, or through the use of extrinsic contrast. A major challenge in applying optical microscopy to in vivo tissue imaging is the effects of light attenuation which limits light penetration depth and achievable imaging resolution. Recently Selective Plane Illumination Microscopy (SPIM) has been used to map the 3D distribution of fluorophores dispersed in biological structures. In this approach, a focused sheet of light is used to illuminate the sample from the side to excite fluorophores within the sample of interest. Images are formed based on detection of fluorescence emission orthogonal to the illumination axis. By scanning the sample along the detection axis and acquiring a stack of images, 3D volumes can be obtained. The combination of rapid image acquisition speeds with the low photon dose to samples optical sectioning provides SPIM is an attractive approach for imaging biological samples in 3D. To date all implementations of SPIM rely on the use of fluorescence reporters be that endogenous or exogenous. This approach has the disadvantage that in the case of exogenous probes the specimens are altered from their native stage rendering them unsuitable for in vivo studies and in general fluorescence emission is weak and transient. Here we present for the first time to our knowledge a label-free implementation of SPIM that has downstream applications in the clinical setting. The experimental set up used in this work incorporates both label-free and fluorescent illumination arms in addition to a high specification camera that can be partitioned for simultaneous imaging of both fluorescent emission and scattered light from intrinsic sources of optical contrast in the sample being studied. This work first involved calibration of the imaging system and validation of the label-free method with well characterised fluorescent microbeads embedded in agarose gel. 3D constructs of mammalian cells cultured in agarose gel with varying cell concentrations were then imaged. A time course study to track cell proliferation in the 3D construct was also carried out and finally a native tissue sample was imaged. For each sample multiple images were obtained by scanning the sample along the axis of detection and 3D maps reconstructed. The results obtained validated label-free SPIM as a viable approach for imaging cells in a 3D gel construct and native tissue. This technique has the potential use in a near-patient environment that can provide results quickly and be implemented in an easy to use manner to provide more information with improved spatial resolution and depth penetration than current approaches.

Keywords: bioimaging, optics, selective plane illumination microscopy, tissue imaging

Procedia PDF Downloads 250

Authors: Dongping Fang, Lian Duan, Xiaojing Yuan, Mike Xu, Allyn Klunder, Kevin Tan, Suiting Cao, Yeqing Ji

Abstract:

Accurate prediction of a medical condition with straight clinical evidence is a long-sought topic in the medical management and health insurance field. Although great progress has been made with machine learning algorithms, the medical community is still, to a certain degree, suspicious about the model's accuracy and interpretability. This paper presents an innovative hierarchical attention deep learning model to achieve good prediction and clear interpretability that can be easily understood by medical professionals. This deep learning model uses a hierarchical attention structure that matches naturally with the medical history data structure and reflects the member’s encounter (date of service) sequence. The model attention structure consists of 3 levels: (1) attention on the medical code types (diagnosis codes, procedure codes, lab test results, and prescription drugs), (2) attention on the sequential medical encounters within a type, (3) attention on the medical codes within an encounter and type. This model is applied to predict the occurrence of stage 3 chronic kidney disease (CKD3), using three years’ medical history of Medicare Advantage (MA) members from a top health insurance company. The model takes members’ medical events, both claims and electronic medical record (EMR) data, as input, makes a prediction of CKD3 and calculates the contribution from individual events to the predicted outcome. The model outcome can be easily explained with the clinical evidence identified by the model algorithm. Here are examples: Member A had 36 medical encounters in the past three years: multiple office visits, lab tests and medications. The model predicts member A has a high risk of CKD3 with the following well-contributed clinical events - multiple high ‘Creatinine in Serum or Plasma’ tests and multiple low kidneys functioning ‘Glomerular filtration rate’ tests. Among the abnormal lab tests, more recent results contributed more to the prediction. The model also indicates regular office visits, no abnormal findings of medical examinations, and taking proper medications decreased the CKD3 risk. Member B had 104 medical encounters in the past 3 years and was predicted to have a low risk of CKD3, because the model didn’t identify diagnoses, procedures, or medications related to kidney disease, and many lab test results, including ‘Glomerular filtration rate’ were within the normal range. The model accurately predicts members A and B and provides interpretable clinical evidence that is validated by clinicians. Without extra effort, the interpretation is generated directly from the model and presented together with the occurrence date. Our model uses the medical data in its most raw format without any further data aggregation, transformation, or mapping. This greatly simplifies the data preparation process, mitigates the chance for error and eliminates post-modeling work needed for traditional model explanation. To our knowledge, this is the first paper on an interpretable deep-learning model using a 3-level attention structure, sourcing both EMR and claim data, including all 4 types of medical data, on the entire Medicare population of a big insurance company, and more importantly, directly generating model interpretation to support user decision. In the future, we plan to enrich the model input by adding patients’ demographics and information from free-texted physician notes.

Keywords: deep learning, interpretability, attention, big data, medical conditions

Procedia PDF Downloads 91