A novel pipeline employing deep multi-attention channels network for the autonomous detection of metastasizing cells through fluorescence microscopy.

Metastasis driven by cancer cell migration is the leading cause of cancer-related deaths. It involves significant changes in the organization of the cytoskeleton, which includes the actin microfilaments and the vimentin intermediate filaments. Understanding how these filament change cells from normal to invasive offers insights that can be used to improve cancer diagnosis and therapy. We have developed a computational, transparent, large-scale and imaging-based pipeline, that can distinguish between normal human cells and their isogenically matched, oncogenically transformed, invasive and metastasizing counterparts, based on the spatial organization of actin and vimentin filaments in the cell cytoplasm. Due to the intricacy of these subcellular structures, manual annotation is not trivial to automate. We used established deep learning methods and our new multi-attention channel architecture. To ensure a high level of interpretability of the network, which is crucial for the application area, we developed an interpretable global explainable approach correlating the weighted geometric mean of the total cell images and their local GradCam scores. The methods offer detailed, objective and measurable understanding of how different components of the cytoskeleton contribute to metastasis, insights that can be used for future development of novel diagnostic tools, such as a nanometer level, vimentin filament-based biomarker for digital pathology, and for new treatments that significantly can increase patient survival.

Preparing Institutions to Implement Harmonized Medicine and Nursing Curricula Through the Use of Cross-Institutional Faculty Developers.

Background: Effective implementation of new curricula requires faculty to be knowledgeable about curriculum goals and have the appropriate pedagogical skills to implement the curriculum, even more so if the new curriculum is being deployed at multiple institutions. In this paper, we describe the process of creating a common faculty development program to train cross-institutional faculty developers to support the implementation of national harmonized medicine and nursing curricula. Methods: A five-step approach was used, including a cross-institutional needs assessment survey for faculty development needs, the development of a generic faculty development program, the identification and training of cross-institutional faculty educators, and the implementation of cross-institutional faculty capacity-building workshops. Results: A list of common cross-cutting faculty development needs for teaching and learning was identified from the needs assessment survey and used to develop an accredited, cross-institutional faculty development program for competency-based learning and assessment. A total of 24 cross-institutional faculty developers were identified and trained in 8 core learning and assessment workshops. A total of 18 cross-institutional and 71 institutional workshops were conducted, of which 1292 faculty members and 412 residents were trained, and three cross-institutional educational research projects were implemented. Conclusion: The success attained in this study shows that the use of cross-institutional faculty developers is a viable model and sustainable resource that can be used to support the implementation of harmonized national curricula.

Mosaic Muir Torre Syndrome: Keratoacanthoma as a Piece of the Puzzle.

ABSTRACT: Lynch syndrome is an inherited condition, which increases the risk of numerous visceral malignancies and cutaneous tumors such as keratoacanthomas and sebaceous tumors. It is typically identified by immunohistochemistry of tissue taken from tumors or through genetic testing with next-generation sequencing. Diagnosing Lynch syndrome becomes more complex when the individual is mosaic for the relevant pathogenic variant. There are very few cases of this reported in the medical literature. It is even more unusual for the diagnosis to be made based on testing of a keratoacanthoma lesion. We report a case where immunohistochemistry of a keratoacanthoma helped make a diagnosis of mosaic Lynch syndrome. We will explore how mosaicism should be considered when a phenotype is strong, even if next-generation sequencing reports no pathogenic or likely pathogenic variant and how lesions such as keratoacanthomas can have a role in the early detection and treatment of future malignancies.

The process of harmonizing competency-based curricula for medicine and nursing degree programmes: A Multi-institutional and multi-professional experience from Tanzania.

In many low- and middle-income countries, there seems to be a mismatch between graduate skills and healthcare industry requirements due to variability in curricula. With the current increased global demand for competent health profession graduates, harmonizing competency-based curricula (CBC) is necessary to address this mismatch. This paper describes how three health professions training universities in Tanzania and their two long-standing United States partners embarked on developing harmonized CBC for undergraduate medicine and nursing degrees. The main goal of the activity was to develop templates to harmonize curricula that would support graduates to acquire mandatory national Graduate Minimum Essential Competencies (GMEC) irrespective of the institution of their training. The paper describes the processes of engaging multiple institutions, the professions of medicine and nursing and various stakeholders to develop mandatory curricula generic competencies, creating milestones for assessing competencies, training faculty at each of the three partnering institutions in curriculum delivery and assessments, resulting in the adoption of the curricula by the University leadership at each institution. Ultimately the Tanzania Commission for Universities (TCU) a regulatory body required all schools of medicine and nursing in the country to adopt the curricula, thus creating a harmonized national standard for teaching medicine and nursing beginning October 2022.

Metastasising Fibroblasts Show an HDAC6-Dependent Increase in Migration Speed and Loss of Directionality Linked to Major Changes in the Vimentin Interactome.

Metastasising cells express the intermediate filament protein vimentin, which is used to diagnose invasive tumours in the clinic. We aimed to clarify how vimentin regulates the motility of metastasising fibroblasts. STED super-resolution microscopy, live-cell imaging and quantitative proteomics revealed that oncogene-expressing and metastasising fibroblasts show a less-elongated cell shape, reduced cell spreading, increased cell migration speed, reduced directionality, and stronger coupling between these migration parameters compared to normal control cells. In total, we identified and compared 555 proteins in the vimentin interactome. In metastasising cells, the levels of keratin 18 and Rab5C were increased, while those of actin and collagen were decreased. Inhibition of HDAC6 reversed the shape, spreading and migration phenotypes of metastasising cells back to normal. Inhibition of HDAC6 also decreased the levels of talin 1, tropomyosin, Rab GDI ß, collagen and emilin 1 in the vimentin interactome, and partially reversed the nanoscale vimentin organisation in oncogene-expressing cells. These findings describe the changes in the vimentin interactome and nanoscale distribution that accompany the defective cell shape, spreading and migration of metastasising cells. These results support the hypothesis that oncogenes can act through HDAC6 to regulate the vimentin binding of the cytoskeletal and cell-extracellular matrix adhesion components that contribute to the defective motility of metastasising cells.

Distinct Biomarker Profiles Distinguish Malawian Children with Malarial and Non-malarial Sepsis.

Presently, it is difficult to accurately diagnose sepsis, a common cause of childhood death in sub-Saharan Africa, in malaria-endemic areas, given the clinical and pathophysiological overlap between malarial and non-malarial sepsis. Host biomarkers can distinguish sepsis from uncomplicated fever, but are often abnormal in malaria in the absence of sepsis. To identify biomarkers that predict sepsis in a malaria-endemic setting, we retrospectively analyzed data and sera from a case-control study of febrile Malawian children (aged 6-60 months) with and without malaria who presented to a community health center in Blantyre (January-August 2016). We characterized biomarkers for 29 children with uncomplicated malaria without sepsis, 25 without malaria or sepsis, 17 with malaria and sepsis, and 16 without malaria but with sepsis. Sepsis was defined using systemic inflammatory response criteria; biomarkers (interleukin-6 [IL-6], tumor necrosis factor receptor-1, interleukin-1 ß [IL-1ß], interleukin-10 [IL-10], von Willebrand factor antigen-2, intercellular adhesion molecule-1, and angiopoietin-2 [Ang-2]) were measured with multiplex magnetic bead assays. IL-6, IL-1ß, and IL-10 were elevated, and Ang-2 was decreased in children with malaria compared with non-malarial fever. Children with non-malarial sepsis had greatly increased IL-1ß compared with the other subgroups. IL-1ß best predicted sepsis, with an area under the receiver operating characteristic (AUROC) of 0.71 (95% CI: 0.57-0.85); a combined biomarker-clinical characteristics model improved prediction (AUROC of 0.77, 95% CI: 0.67-0.85). We identified a distinct biomarker profile for non-malarial sepsis and developed a sepsis prediction model. Additional clinical and biological data are necessary to further explore sepsis pathophysiology in malaria-endemic regions.

Breast Cancer knowledge, perceptions and practices in a rural Community in Coastal Kenya.

BACKGROUND: Data on breast healthcare knowledge, perceptions and practice among women in rural Kenya is limited. Furthermore, the role of the male head of household in influencing a woman's breast health seeking behavior is also not known. The aim of this study was to assess the knowledge, perceptions and practice of breast cancer among women, male heads of households, opinion leaders and healthcare providers within a rural community in Kenya. Our secondary objective was to explore the role of male heads of households in influencing a woman's breast health seeking behavior. METHODS: This was a mixed method cross-sectional study, conducted between Sept 1st 2015 Sept 30th 2016. We administered surveys to women and male heads of households. Outcomes of interest were analysed in Stata ver 13 and tabulated against gender. We conducted six focus group discussions (FGDs) and 22 key informant interviews (KIIs) with opinion leaders and health care providers, respectively. Elements of the Rapid Assessment Process (RAP) were used to guide analysis of the FGDs and the KIIs. RESULTS: A total of 442 women and 237 male heads of households participated in the survey. Although more than 80% of respondents had heard of breast cancer, fewer than 10% of women and male heads of households had knowledge of 2 or more of its risk factors. More than 85% of both men and women perceived breast cancer as a very serious illness. Over 90% of respondents would visit a health facility for a breast lump. Variable recognition of signs of breast cancer, limited decision- autonomy for women, a preference for traditional healers, lack of trust in the health care system, inadequate access to services, limited early-detection services were the six themes that emerged from the FGDs and the KIIs. There were discrepancies between the qualitative and quantitative data for the perceived role of the male head of household as a barrier to seeking breast health care. CONCLUSIONS: Determining level of breast cancer knowledge, the characteristics of breast health seeking behavior and the perceived barriers to accessing breast health are the first steps in establishing locally relevant intervention programs.

Utilization of health services in a resource-limited rural area in Kenya: Prevalence and associated household-level factors.

BACKGROUND AND METHODS: Knowledge of utilization of health services and associated factors is important in planning and delivery of interventions to improve health services coverage. We determined the prevalence and factors associated with health services utilization in a rural area of Kenya. Our findings inform the local health management in development of appropriately targeted interventions. We used a cluster sample survey design and interviewed household key informants on history of illness for household members and health services utilization in the preceding month. We estimated prevalence and performed random effects logistic regression to determine the influence of individual and household level factors on decisions to utilize health services. RESULTS AND CONCLUSIONS: 1230/6,440 (19.1%, 95% CI: 18.3%-20.2%) household members reported an illness. Of these, 76.7% (95% CI: 74.2%-79.0%) sought healthcare in a health facility. The majority (94%) of the respondents visited dispensary-level facilities and only 60.1% attended facilities within the study sub-counties. Of those that did not seek health services, 43% self-medicated by buying non-prescription drugs, 20% thought health services were too costly, and 10% indicated that the sickness was not serious enough to necessitate visiting a health facility. In the multivariate analyses, relationship to head of household was associated with utilization of health services. Relatives other than the nuclear family of the head of household were five times less likely to seek medical help (Odds Ratio 0.21 (95% CI: 0.05-0.87)). Dispensary level health facilities are the most commonly used by members of this community, and relations at the level of the household influence utilization of health services during an illness. These data enrich the perspective of the local health management to better plan the allocation of healthcare resources according to need and demand. The findings will also contribute in the development of community-level health coverage interventions that target the disadvantaged household groups.

Population Health Science: A Core Element of Health Science Education in Sub-Saharan Africa.

Sub-Saharan Africa suffers an inordinate burden of disease and does not have the numbers of suitably trained health care workers to address this challenge. New concepts in health sciences education are needed to offer alternatives to current training approaches.A perspective of integrated training in population health for undergraduate medical and nursing education is advanced, rather than continuing to take separate approaches for clinical and public health education. Population health science educates students in the social and environmental origins of disease, thus complementing disease-specific training and providing opportunities for learners to take the perspective of the community as a critical part of their education.Many of the recent initiatives in health science education in sub-Saharan Africa are reviewed, and two case studies of innovative change in undergraduate medical education are presented that begin to incorporate such population health thinking. The focus is on East Africa, one of the most rapidly growing economies in sub-Saharan Africa where opportunities for change in health science education are opening. The authors conclude that a focus on population health is a timely and effective way for enhancing training of health care professionals to reduce the burden of disease in sub-Saharan Africa.

Where teachers are few: documenting available faculty in five Tanzanian medical schools.

BACKGROUND: Faced with one of the lowest physician-to-population ratios in the world, the Government of Tanzania is urging its medical schools to train more physicians. The annual number of medical students admitted across the country rose from 55 in the 1990s to 1,680 approved places for the 2015/16 academic year. These escalating numbers strain existing faculty. OBJECTIVE: To describe the availability of faculty in medical schools in Tanzania. DESIGN: We identified faculty lists published on the Internet by five Tanzanian medical schools for the 2011/12 academic year and analyzed the appointment status, rank, discipline, and qualifications of faculty members. RESULTS: The five schools reported 366 appointed faculty members (excluding visiting, part-time, or honorary appointments) for an estimated total enrolled student capacity of 3,275. Thirty-eight percent of these faculty were senior lecturers or higher. Twenty-seven percent of the appointments were in basic science, 51% in clinical science, and 21% in public health departments. The most populated disciplines (more than 20 faculty members across the five institutions) were biochemistry and molecular biology, medicine, obstetrics and gynecology, pediatrics, and surgery; the least populated disciplines (less than 10 faculty members) were anesthesiology, behavioral sciences, dermatology, dental surgery, emergency medicine, hematology, ophthalmology, orthopedics, otorhinolaryngology, oncology and radiology, psychiatry. These figures are only indicative of faculty numbers because of differences in the way the schools published their faculty lists. CONCLUSIONS: Universities are not recruiting faculty at the same rate that they are admitting students, and there is an imbalance in the distribution of faculty across disciplines. Although there are differences among the universities, all are struggling to recruit and retain staff. If Tanzanian universities, the government, donors, and international partners commit resources to develop, recruit, and retain new faculty, Tanzania could build faculty numbers to permit a quality educational experience for its doctors of tomorrow.

Modeling solutions to Tanzania's physician workforce challenge.

BACKGROUND: There is a great need for physicians in Tanzania. In 2012, there were approximately 0.31 physicians per 10,000 individuals nationwide, with a lower ratio in the rural areas, where the majority of the population resides. In response, universities across Tanzania have greatly increased the enrollment of medical students. Yet evidence suggests high attrition of medical graduates to other professions and emigration from rural areas where they are most needed. OBJECTIVE: To estimate the future number of physicians practicing in Tanzania and the potential impact of interventions to improve retention, we built a model that tracks medical students from enrollment through clinical practice, from 1990 to 2025. DESIGN: We designed a Markov process with 92 potential states capturing the movement of 25,000 medical students and physicians from medical training through employment. Work possibilities included clinical practice (divided into rural or urban, public or private), non-clinical work, and emigration. We populated and calibrated the model using a national 2005/2006 physician mapping survey, as well as graduation records, graduate tracking surveys, and other available data. RESULTS: The model projects massive losses to clinical practice between 2016 and 2025, especially in rural areas. Approximately 56% of all medical school students enrolled between 2011 and 2020 will not be practicing medicine in Tanzania in 2025. Even with these losses, the model forecasts an increase in the physician-to-population ratio to 1.4 per 10,000 by 2025. Increasing the absorption of recent graduates into the public sector and/or developing a rural training track would ameliorate physician attrition in the most underserved areas. CONCLUSIONS: Tanzania is making significant investments in the training of physicians. Without linking these doctors to employment and ensuring their retention, the majority of this investment in medical education will be jeopardized.

Image training, using random images of melanoma, performs as well as the ABC(D) criteria in enabling novices to distinguish between melanoma and mimics of melanoma.

Robust experimental evidence supporting many attempts to facilitate early melanoma diagnosis is lacking. In an experimental study using a browser interface we have examined diagnostic accuracy, sensitivity and specificity of novices in distinguishing between melanomas and mimics of melanoma. We show that rule-based ABC methods and image training, based on random images of melanoma, improve specificity to similar degrees, with-out effects on sensitivity, leading to small improvements in overall accuracy. There was a significant effect of age with older subjects performing better. Although both the ABC method and image training groups showed improved performance over the control group, overall performance was poor. For instance, for a task in which 1 in 4 test images was a melanoma, and 3 out of 4 benign, both interventions (ABC or image training) increased accuracy from the control value of 53% to around 61%. For reference, dermatology trainees performed at a much higher level of accuracy. Our study provides little support for the use of such methods in public education, but suggests ways in which performance might be improved.

Mekong Basin Disease Surveillance (MBDS): a trust-based network.

The Mekong Basin Disease Surveillance (MBDS) network was formally established in 2001 through a Memorandum of Understanding signed by six Ministers of Health of the countries in the Greater Mekong sub-region: Cambodia, China (Yunnan and Guangxi), Lao PDR, Myanmar, Thailand and Vietnam. The main areas of focus of the network are to: i) improve cross-border infectious disease outbreak investigation and response by sharing surveillance data and best practices in disease recognition and reporting, and by jointly responding to outbreaks; ii) develop expertise in epidemiological surveillance across the countries; and iii) enhance communication between the countries. Comprised of senior health officials, epidemiologists, health practitioners, and other professionals, the MBDS has grown and matured over the years into an entity based on mutual trust that can be sustained into the future. Other regions have started emulating the network's pioneering work. In this paper, we describe the development of MBDS, the way in which it operates today, and some of its achievements. We present key challenges the network has faced and lessons its members have learned about how to develop sufficient trust for health and other professionals to alert each other to disease threats across national borders and thereby more effectively combat these threats.

The evolution and expansion of regional disease surveillance networks and their role in mitigating the threat of infectious disease outbreaks.

We examine the emergence, development, and value of regional infectious disease surveillance networks that neighboring countries worldwide are organizing to control cross-border outbreaks at their source. The regional perspective represented in the paper is intended to serve as an instructive framework for others who decide to launch such networks as new technologies and emerging threats bring countries even closer together. Distinct from more formal networks in geographic regions designated by the World Health Organization (WHO), these networks usually involve groupings of fewer countries chosen by national governments to optimize surveillance efforts. Sometimes referred to as sub-regional, these "self-organizing" networks complement national and local government recognition with informal relationships across borders among epidemiologists, scientists, ministry officials, health workers, border officers, and community members. Their development over time reflects both incremental learning and growing connections among network actors; and changing disease patterns, with infectious disease threats shifting over time from local to regional to global levels. Not only has this regional disease surveillance network model expanded across the globe, it has also expanded from a mostly practitioner-based network model to one that covers training, capacity-building, and multidisciplinary research. Today, several of these networks are linked through Connecting Organizations for Regional Disease Surveillance (CORDS). We explore how regional disease surveillance networks add value to global disease detection and response by complementing other systems and efforts, by harnessing their power to achieve other goals such as health and human security, and by helping countries adapt to complex challenges via multi-sectoral solutions. We note that governmental commitment and trust among participating individuals are critical to the success of regional infectious disease surveillance networks.

Partnering on education for health: Muhimbili University of Health and Allied Sciences and the University of California San Francisco.

In 2005, Muhimbili University of Health and Allied Sciences (MUHAS) in Tanzania and the University of California San Francisco (UCSF) in the United States joined to form a partnership across all the schools in our institutions. Although our goal is to address the health workforce crisis in Tanzania, we have gained much as institutions. We review the work undertaken and point out how this education partnership differs from many research collaborations. Important characteristics include: (i) activities grew out of MUHAS's institutional needs, but also benefit UCSF; (ii) working across professions changed the discourse from 'medical education' to 'health professions education'; (iii) challenged by gaps in our respective health-care systems, both institutions chose a new focus, interprofessional team work; (iv) despite being so differently resourced, MUHAS and UCSF seek strategies to address growing class sizes; and (v) we involved a wider range of people - faculty, administrators, students, and residents - at both institutions than is usually the case with research. This partnership has convinced us to exhort other academic leaders in the health arena to seek opportunities together to enlighten and enliven our educational enterprises.

First steps towards interprofessional health practice in Tanzania: an educational experiment in rural Bagamoyo district.

Health workers in Tanzania struggle to provide adequate health care for populations with high maternal, neonatal, and child mortality and high prevalence of communicable and non-communicable diseases. There are longstanding shortages of staff and resources. Universities are training more health professionals and revising curricula to be sure that staff have the specific skills needed to work in rural districts. This includes training people from different disciplines to work more effectively together. While teamwork is important in all settings, it is particularly critical in rural areas where there are few trained professionals. The health professional schools at Muhimbili University of Health and Allied Sciences (MUHAS) developed curricula that share common competencies to promote interprofessional cooperation. In this article, we describe a pilot program developed by MUHAS to train its professional students (dentists, doctors, environmental health officers, nurses, and pharmacists) to work collaboratively with each other and with other health staff at the district level. We describe the reactions of participants, and identify some considerations for taking such an exercise to scale for education.

Teaching and educational scholarship in Tanzania: faculty initiative to improve performance of health professions' students.

Well-educated and competent health professionals influence the health system in which they work to improve health outcomes, through clinical care and community interventions, and by raising standards of practice and supervision. To prepare these individuals, training institutions must ensure that their faculty members, who design and deliver education, are effective teachers. We describe the experience of the Muhimbili University of Health and Allied Sciences (MUHAS) in encouraging improvements in the teaching capacity of its faculty and postgraduate students triggered by a major institutional transition to competency-based education. We employed a multi-stage process that started by identifying the teaching and learning needs and challenges of MUHAS students and faculty. Collaborating with the University of California San Francisco (UCSF), MUHAS responded to these needs by introducing faculty to competency-based curricula and later to strategies for long term continuing improvement. We demonstrate that teaching faculty members are keen for local institutional support to enable them to enhance their skills as educators, and that they have been able to sustain a program of faculty development for their peers.

Health professions educators as agents of change in Tanzania: creativity to implement new curricula.

Muhimbili University of Health and Allied Sciences (MUHAS) strives to instill in its graduates skills and competencies appropriate to serving the Tanzanian population well. MUHAS leadership, working in collaboration with educators from the University of California San Francisco (UCSF), selected and trained an interdisciplinary group of faculty members to promote effective teaching. We describe the development of this group of faculty change agents - now known as the Health Professions Educators Group (HPEG). The HPEG invigorated the education environment at MUHAS by: engaging many colleagues in special training events that introduced new methods for teaching and assessment; encouraging innovation; and developing strong mentoring relationships. HPEG members piloted courses in education to prepare all postgraduate students as peer educators, teaching assistants, and as candidates for faculty future appointments. Creation of a 'teaching commons' reinforces the new focus on innovative teaching as faculty members share experiences and gain recognition for their contributions to quality education.

An institutional research agenda: focusing university expertise in Tanzania on national health priorities.

A well-articulated institutional health research agenda can assist essential contributors and intended beneficiaries to visualize the link between research and community health needs, systems outcomes, and national development. In 2011, Tanzania's Muhimbili University of Health and Allied Sciences (MUHAS) published a university-wide research agenda. In developing the agenda, MUHAS leadership drew on research expertise in its five health professional schools and two institutes, its own research relevant documents, national development priorities, and published literature. We describe the process the university underwent to form the agenda and present its content. We assess MUHAS's research strengths and targets for new development by analyzing faculty publications over a five-year period before setting the agenda. We discuss implementation challenges and lessons for improving the process when updating the agenda. We intend that our description of this agenda-setting process will be useful to other institutions embarking on similar efforts to align research activities and funding with national priorities to improve health and development.

Tracking university graduates in the workforce: information to improve education and health systems in Tanzania.

With a severe shortage of highly trained health professionals, Tanzania must make the best possible use of available human resources and support training institutions to educate more graduates. We highlight the overlooked but significant role of universities in collecting, managing, and using human resources data in Tanzania and in other countries struggling to build their health workforces. Although universities, professional councils, ministries of health, education, and finance, and non-governmental organizations in Tanzania all maintain databases that include details of health professionals' education, registration, and employment, they do not make the information easily accessible to one another. Using as an example Muhimbili University of Health and Allied Sciences - the leading public institution for health professions education in Tanzania - we explore how training institutions can gather and use data to target and improve the quality of education for increasing numbers of graduates. We specifically examine the substantial challenge universities face in locating more members of each graduating class and conclude with recommendations about how the situation can be improved.