All posts by Ulysses Labilles, DMD, PhD

”Every dream comes from a speck of hope. It is through hope where we gain our strength to make a change."

A Priori Tumor Grading Scale to Triage and Schedule Post COVID-19 Mohs Surgery Patients

The United States is slowly relaxing stay-at-home orders and reopening businesses to reverse the nation’s ailing economy after the spread of the coronavirus that killed millions of jobs and pummeled the global economy. The virus was initially identified as a cluster of pneumonia cases in Wuhan, Hubei Province of China. Later reclassified as a Novel Coronavirus on December 31, 2019, by the World Health Organization (WHO), and health experts in the US, Canada, Germany, Russia, China, Korea, Japan, and Nigeria declared COVID-19 as a Global Pandemic. During the peak of the COVID pandemic, the Centers for Disease and Prevention, the U.S. Centers for Medicare and Medicaid Services, and professional organizations issued countermeasures to flatten the curve, such as elective surgical procedure cancellation. The coronavirus infections are still on the upswing in Texas, Arizona, Florida, and Utah.

A system to forecast the transmission of the virus based on live and current data is critical (Petropoulos & Makridakis, 2020). Cumulative first wave data aggregated nationally and globally could provide accurate forecasting of probable second wave COVID-19 transmission. While accurate forecasting of the virus’s spread is essential, it is critical to establish guidelines to avoid a Coronavirus rebound and frivolous lawsuits that could stunt economic recovery. In the absence of liability protection that shields medical facilities, and employers, it is critical to developing a scheduling point system that controls the number of patients in the waiting area that could be exposed to the asymptomatic transmission of COVID-19. Even with robust liability protection, negligent facilities could still be punished and be sued for damages. The average wait period is 18 minutes during a medical visit. The patients have enough time to mingle, increasing the probability of transmission of infectious diseases based on the amount and nature of contacts between healthy and infected individuals (Goscé & Johansson, 2018). A priori tumor grading scale in scheduling Mohs patients in the post-COVID period as it relates to the parameters for diffusion is vital for the safety and protection of both the patients and healthcare workers. Depending on the tumor grade, the overall degree of connectivity, comorbidity in association to tumor history using the Labilles “United Paradigm of Cancer Causation” (2017), the patient needs to be seen as the earliest. The grading scale introduced on the “Manual of Frozen Section Processing for Mohs Micrographic Surgery” (2008) is an urgency-scoring system to assist Mohs surgeons, administrators, and staff in triaging surgery patients.

References

Beggs, C. B., Shepherd, S. J., & Kerr, K. G. (2010). Potential for airborne transmission of infection in the waiting areas of healthcare premises: stochastic analysis using a Monte Carlo model. BMC infectious diseases10(1), 247.

Franczyk, B. (2019, July). An Intelligent and Data-Driven Decision Support Solution for the Online Surgery Scheduling Problem. In Enterprise Information Systems: 20th International Conference, ICEIS 2018, Funchal, Madeira, Portugal, March 21-24, 2018, Revised Selected Papers (Vol. 363, p. 82). Springer.

Friedman, E., Friedman, J., Johnson, S., & Landsberg, A. (2020). Transitioning out of the coronavirus lockdown: A framework for zone-based social distancing. arXiv preprint arXiv:2004.08504.

Goscé, L., & Johansson, A. (2018). Analysing the link between public transport use and airborne transmission: mobility and contagion in the London underground. Environmental Health17(1), 84.

Labilles, U. (2017). Pathopoiesis mechanism of smoking and shared genes in pancreatic cancer (Copyright Registration No. TX0008490984) [Ph.D. dissertation, Walden University]. ProQuest Dissertations Publishing.

McCulloch, Hetzer, Geddis, McConnell, Brock, Keating, Labilles, Marino, Beck, Wade & Fisher (2008). Manual of Frozen Section Processing for Mohs Micrographic Surgery. In F. Fish III (Ed.). Labilles, U, Immunohistochemistry (p.1201). American College of Mohs Surgery.

Petropoulos, F., & Makridakis, S. (2020). Forecasting the novel coronavirus COVID-19. PloS one15(3), e0231236.

IN THE CONTEXT OF DATA COLLECTION — IS BIGGER BETTER? Can big data help in our fight against COVID-19?

Color logo with backgroundThe traditional researcher concept that big data equates statistical significance should not eclipse the importance of understanding the interrelationship between the effect size, power, and sample size that could translate to both practical and statistical significance. It is critical to be guided by a working theory that gives birth to a useful solution to any given problem, such as in cancer epidemiology, most importantly, to the current COVID-19 pandemic. In 2017, the ”Unified Paradigm of Cancer Causation (UPCC),” a metatheory on cancer epidemiology, was introduced. The premise of this theory can be used in contact tracing as it relates to correlation with socio-behavioral risk factors, environmental interaction, and demographic determinants (SEDD). Understanding the trajectory of COVID-19 transmission could benefit from lessons learned from past and existing legal measures on efficient delivery of emergency and disaster relief not only by updating research reporting protocols but using a theory that bridge the gap between the federal, state, and local government. Petropoulos and Makridakis (2020) highlighted the integral significance of investigating the unknown variables associated with COVID-19 transmission. It is vital to explore the compounding factors that derail emergency relief. Should there be an improved, coordinated effort from the federal, state, and local governments? Are there other compounding factors in establishing an effective strategy in flattening the curve? In the next series, the questions on the COVID-19 epidemiology and its impact on Public Health will be explored, as well as how vital to streamline the Public Health Emergency Preparedness and Disaster Relief Systems. Months after the first case of the virus in the U.S, should we already have started establishing a seasonality pattern prediction protocol? This protocol does include not only age-specific social dynamics but also other compounding factors that complicate the public health countermeasure on social distancing?

It is crucial to adopt real-time modeling that is not only a computational algorithm but provides timely availability of relevant data, as stated by Birrell et al. (2020). Interdisciplinary collaboration both the U.S. and globally must embrace the promise of real-time modeling that provides a timely, relevant data available that could produce a novel cutting edge support tool and methodology for emergency and disaster management and public health policy.

References

Birrell, P. J., Wernisch, L., Tom, B. D., Held, L., Roberts, G. O., Pebody, R. G., & De Angelis, D. (2020). Efficient real-time monitoring of an emerging influenza pandemic: How feasible?. Annals of Applied Statistics14(1), 74-93.

Labilles, U. (2016). The New Public Health: Beyond Genetics and Social Inequalities. Unpublished manuscript, College of Health Sciences, Public Health, Epidemiology, Walden University, Minneapolis.

Labilles, U. (2017). Pathopoiesis Mechanism of Smoking and Shared Genes in Pancreatic Cancer.

Olson, D. R., Lopman, B. A., Konty, K. J., Mathes, R. W., Papadouka, V., Ternier, A., … & Pitzer, V. E. (2020). Surveillance data confirm multiyear predictions of rotavirus dynamics in New York City. Science advances6(9), eaax0586.

Petropoulos, F., & Makridakis, S. (2020). Forecasting the novel coronavirus COVID-19. PloS one15(3), e0231236.

Educational Gamification Design Principles and Formative Feedbacks: Overcoming Inappropriate Postings in Discussion Thread

What is Gamification? Gamification is the craft of deriving all the fun and addicting elements found in games (Konopelko & O’Broin,2017) and applied in real-world activities such as learning. Dealing with a learner who posted something inappropriate in a discussion, immediate short feedback using alternative means of communication such as the “message tool” or a private feedback discussion area for a private message is essential to guide the student to the right track following the prescribed rubric of the assigned topic. Incorporating education gamification design principles in combination with formative feedbacks make the learning experience more fun, more “real” and engaging, leading to the perceived enhanced value of the educational exercise.

The education gamification design principle “Freedom to fail” as stated by Haaranen et al., (2014), Berkling and Thomas, (2013), De Byl and Hooper, (2013), Hentenryck and Coffrin, (2014)) presumes no penalties on poor choice or task performance allowed students to revise and re-submit assignments, or go back to the discussion thread and post a relevant argument. Then the student will have the chance to reclaim the conversation, and apply the principle “Freedom of choice” where he/she could weave together the contributions of other students in the class. In this way, as educators, we show empathy; at the same time, help our learners develop empathy. We have the chance in this scenario, to remove the notion of a “tribe of one,” loyal to one party, but rather induce collaboration for the better good. It will add up to a flight of discussion and rebuttal, nurturing a conversation of ideas, a forum where creative partnership thrive. Hybrid formative feedbacks could promote interest and the drive to deeply engage in a discussion forum, transforming the gaming concept to positive addictive behavior that encourages collective intelligence (CI). CI or group intelligence in a class will then eclipse any inappropriate discussion post and reverse the probable implication of negativity to positivity. Feedback to students that is informed by insights derived from both personal and professional experience make the feedback process “more real” to support one’s development as a reflective, resilient, and humanistic professional in their field of choice. Formative feedbacks can illuminate students’ personal and professional growth.

References

Berkling, K., & Thomas, C. (2013). Gamification of a Software Engineering course and a detailed analysis of the factors that lead to it’s failure. Int. Conference on Interactive Collaborative Learning, (pp. 525–530). Kazan, Russia. doi:10.1109/ICL.2013.6644642

De Byl, P., & Hooper, J. (2013). Key Attributes of Engagement in a Gamified Learning Environment. 30th ASCILITE Conference, (pp. 221–229).

Haaranen, L., Ihantola, P., Hakulinen, L., & Korhonen, A. (2014). How (not) to introduce badges to online exercises. In J. Dougherty, & K. Nagel (Ed.), SIGCSE ’14 (pp. 33–38). Atlanta, GA: ACM.

Hentenryck, P. V., & Coffrin, C. (2014). Teaching Creative Problem Solving in a MOOC. In J. Dougherty, & K. Nagel (Ed.), SIGCSE’14 (pp. 677–682). Atlanta, GA: ACM

Konopelko, M., & O’Broin, D., (2017). Helping Students to Internalise Standards Through Gamification. European Conference on Games Based Learning, 890.

Turkle, S., (2016). Reclaiming conversation: The power of talk in a digital age. Penguin.

Wald, H. S., & Weiss, B. (2018). Making it “More Real”: Using Personal Narrative in Faculty Feedback to a Medical Student’s Reflective Writing–An Illustrative Exemplar. MedEdPublish, 7.

Blast from the Past: Revisiting the Significance of Therapeutic Potential of Psilocybin

Research on the therapeutic potential of psychedelic drugs fell into a hiatus in the past decades until scientists from the United States, Switzerland, and Germany began its revival, exploring its biochemical and physiologic effects in combination with psychotherapy. In the 1950s to the mid-1960s, tens of thousands of patients are estimated to have been treated by psychedelic drugs such as psilocybin because of its unique potency, but its therapeutic promise was eclipsed by countercultural movements (Carhart-Harris, & Goodwin, 2017). Psilocybin, a naturally occurring plant alkaloid found in Psilocybe genus of mushrooms, popularly known as “magic mushrooms” may have been used for healing purposes for many years, (Carhart-Harris et al., 2016), but its pharmacodynamic significance needs high-quality clinical trials to earn medical justification. COMPASS Pathways was recently approved by the US Food and Drug Administration (FDA) for a clinical trial of psilocybin therapy for treatment-resistant depression (TRD).  A life sciences company with the primary intent of accelerating patient access to evidence-based innovation in mental health, COMPASS Pathways will springboard landmark trials across North America and Europe, including the UK and other countries, after regulatory approvals. Phase III studies will be dependent upon the success of these trials.

Globally, the burden of the high prevalence of TRD in the primary care setting justifies the need for a more clinician-led proactive approach to improving the outcome of patient management. While the 2016 study of Carhart-Harris et al. provides preliminary support for safety and efficacy of psilocybin for treatment of TRD, the study highlighted the importance of further trials with a more rigorous design. However, the lack of single definition of what constitutes ‘treatment resistance’ as noted by Thomas et al. (2013), made it critical to stratify research participants based on treatment resistance in association to non-adherence to medication, treatment resistance attributable to failure to respond after antidepressant medication to the more complex medication non-response classification systems. The FDA approval for COMPASS Pathways to conduct a Phase IIb trial will help amplify current knowledge on the effect of psilocybin on depression. Major depression has been ranked by the World Health Organization (WHO) as the fourth leading contributor to the global burden of disease and is expected to be top of the ranking by 2030 (Erritzoe et al., 2018). According to  George Goldsmith, COMPASS Pathways Chairman/Co-founder, and Ekaterina Malievskaia, Chief Medical Officer/Co-founder, the collaborative effort among scientists, clinicians, patient representatives and regulators from Europe and North America will give us evidence-based understanding of the efficacy of psilocybin therapy, as well as assess the safety and positive outcome of this new approach. The study will be the largest psychoactive care clinical trial following numerous academic early reviews on psilocybin’s pharmacodynamic and pharmacokinetic promise in improving the management outcome of TRD. Completion of COMPASS Pathways studies will raise awareness on the safety and efficacy of this novel protocol that could be benefited by patients with depression who failed to respond with either cognitive psychotherapy or medication. Removing psychological defenses as the original rationale of using psychedelic drugs in combination with psychotherapy, endorses the findings of Watts et al. (2017) on the increased amygdala (right amygdala) responses suggestive to positive mood effects and alleviation of depressive symptoms of psychedelics (Roseman et al., 2017). The continued focus on therapeutic interventions with evidence-based alternative strategies is critical in easing the socio-economic burden and improving the prognosis of TRD.

 

References

Carhart-Harris, R., Bolstridge, M., Rucker, J., Day, C., Erritzoe, D., Kaelen, M., Bloomfield, M., Rickard. J., Forbes, B., Feilding, A., Taylor, D., Pilling, S., Curran, V., Nutt, D. (2016). Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. Lancet Psychiatry. 3, 619-27. doi: https://doi.org/10.1016/S2215-0366(16)30065-7

Carhart-Harris, R., & Goodwin, G. (2017). The Therapeutic Potential of Psychedelic Drugs: Past, Present, and Future. Neuropsychopharmacology, 1-9. doi: http://dx.doi.org/10.1038/npp.2017.84

Erritzoe, D., Roseman, L., Nour, M., MacLean, K., Kaelen, M., Nutt, D.J., Carhart-Harris, R.L. (2018). Effects of psilocybin therapy on personality structure. Acta Psychiatrica Scandinavica, 1–11. doi: 10.1111/acps.12904

Hermle L., Oepen G., Botsch H., Borchardt D., Gouzoulis E. et al. (1992). Mescaline-induced psychopathological, neuropsychological, and neurometabolic effects in normal subjects: experimental psychosis as a tool for psychiatric research. Biol Psychiatry, 32: 976–991. doi: http://dx.doi.org/10.1016/0006-3223(92)90059-9

Roseman, L., Demetriou, L., Wall, M., Nutt, D., Carhart-Harris, R. (2017). Increased amygdala responses to emotional faces after psilocybin for treatment-resistant depression. Neuropharmacology, 1-7. doi: https://doi.org/10.1016/j.neuropharm.2017.12.041

Strassman R., Qualls C. (1994). Dose-response study of N,Ndimethyltryptamine in humans. I. Neuroendocrine, autonomic, and cardiovascular effects. Arch Gen Psychiatry, 51: 85–97.

The Global Strategy Final – WHO. (n.d.). Retrieved from http://www.who.int/substance_abuse/alcstratenglishfinal.pdf?ua=1

Thomas, L., Kessler, D., Campbell, J., Morrison, J., Peters, T., Williams, C., Lewis, G., Wiles, N. (2013). Prevalence of treatment-resistant depression in primary care: a cross-sectional study. British Journal of General Practice. e852-e858. doi: http://dx.doi.org/10.3399/bjgp13X675430

Vollenweider F., Leenders K., Scharfetter C., Maguire P., Stadelmann O., Angst J. (1997). Positron emission tomography and fluorodeoxyglucose studies of metabolic hyperfrontality and psychopathology in the psilocybin model of psychosis. Neuropsychopharmacology, 16: 357–372. doi: http://dx.doi.org/10.1016/S0893-133X(96)00246-1

 

Bridging Cancer Epidemiology and Social Evolution

Research Design 2Modern epidemiology is a direct result of the paradigm shift from a population-based (upstream) to a downstream (individual) approach. The impact of modern epidemiology such as ‘molecular’ and ‘genetic’ epidemiology (Loomis & Wing, 1990; Diez-Roux, 1998) requires an explanatory power that mostly dependent upon the advances in technology and information systems. Moreover, before estimating the economic effect of a specific intervention before it is implemented, nor assess the economic and/or quality-of-life value of an ongoing or anticipated intervention (Rothermel, 2013); it is critical to recognize not only the significance of sophisticated technologies that go beyond the established genome, proteome, and gene expression platforms, but also new techniques of study design and data analysis (Pearce, 1996; Verma, Khoury & Ioannidis, 2013). Given the remarkable progress in the last decade in advanced technology and new methods for biologic measurements, the reductionist approach of modern epidemiology often ignored the significant causes of disease. Pearce (1996) argue that epidemiology must reintegrate itself into public health and must rediscover the population perspective. However, while the new paradigm could produce a lifestyle approach to social policy, the cumulative outcome of research in cancer epidemiology could equate positive implications to population health.

The key figures in the new epidemiologic model not only acknowledges the development of new techniques of study design and data analysis but also recognize the need for a multidisciplinary approach (social, biologic, statistical), and specifying the population group as the unit of study (Susser, 1985). While occupational carcinogens can be controlled with some difficulty through regulatory measures (Pearce, 1996), it is essential to acknowledge the fundamental problem of tobacco use, not by its consumption but in its production. Pearch (1996) focused on some of these fundamental changes in epidemiology over the past few decades and considered the concepts of causality involved, as well as their ideological and practical consequences. While smoking cessation could be the probable social implication, it is important to stress the epidemiologic value of a study on the apparent correlation between gender and age, modification effect of tobacco use among individuals with pancreatic cancer (PC) and cancer types with a shared-gene association (CTSG-A). The outcome of a risk factor epidemiologic study in individual terms could uplift precision medicine to meet the challenges in tailoring medical interventions based on patient’s biological profile, genetic and epigenetic traits, giving a better understanding of the environment, genetic, biodemographic interactions (EGBIs).

Embraced by both biomedical and social determinist frameworks, the interlinking of the traditional epidemiologic level of intervention (upstream or distal) and the modern epidemiologic level of intervention (downstream or proximal) put public health in the conundrum of the proximal-distal divide. Signal the importance of the argument of the 2008 study of Krieger in replacing the terms proximal and distal from the public health lexicon, supports the recommendation of Wemrell et al. (2016) on the critical need for open interdisciplinary debates on the contribution of social theory to the epidemiological inquiry. While coping with the demand of the 21st-century, global health could still be viewed and approached within the mindset of traditional epidemiology, and the purview of molecular and cancer epidemiology.

The discovery of tobacco smoking as a cause of lung cancer in the early 1950s gave the field of epidemiology its recognition (Pearce, 1996), shifting the epidemiologic paradigm in the object of study in the mid-20th century on the role of multiple causes. Establishing the correlation of age, gender a modifiable risk factor (smoking) with PC and CTSG-A requires the use of early and current epidemiologic theories, and contemporary mainstream epidemiologic concept coalescing to a United Paradigm of Cancer Causation (UPCC). The complex, integrative approach of UPCC supports the views of Loomis, and Wing (1990), Pearce (1996), and McEwen and Getz (2013) in embracing the new epidemiologic paradigm congruent to the advances in cancer genome sequencing. Theorizing the pathopoiesis mechanism of smoking, inherited genes, and association of gender and age in the etiopathogenesis of PC/CTSG-A warrants exploration of its causal footprints, conjoining both biomedical and lifestyle (Krieger, 2011).

Follow-up and future research on the role of molecular epidemiology in emphasizing individual susceptibility to PC will assess the relative contribution of modifiable risk factors to non-modifiable genetic factors. In this premise, the etiopathogenesis of the disease could be explored from the bottom up. Bridging cancer epidemiology and social evolution will be dependent upon the incorporation of the strength of the social network and social contagion theory. The testable assumption of the social network theory as its strength states that the social structure of the network itself be primarily responsible for determining individual behavior and attitudes by shaping the flow of resources which determines access to opportunities and constraints on behavior (Berkman et al., 2000). Why choose if a single theory cannot make a change? Incorporating these ideas in addition to the composite and underpinnings of UPCC could springboard a priori argument on the role of social networks in the spread of an intervention such as smoking cessation, or amplifying the promotion of the significance of early screening to improve mortality and morbidity.

While the causal nature of peer effects could be associated with tobacco use; the social contagion theory of Christakis and Fowler (2013) set an argument on human social networks exhibiting a “three degrees of separation.” Such association could support the assumption of spreading the interpersonal influence that acknowledges the significance of early screening, and the promise of a novel therapeutic approach. Like the widely discussed classic paper of Travers and Milgram (1969) on ‘six degrees of separation,’ the three degrees of separation or the three degrees of separation rule (Christakis & Fowler, 2009) agreed on the premise that telegraph phrases are meant to be evocative, and not definitive. For example, the role of interpersonal influence in spreading novel ideas such as advances in early screening to achieve a more significant therapeutic outcome. The preponderance of the evidence that points to the added significance of a passive-broadcast viral messaging to create social contagion warrants the recognition of the approach. Taking into account factors such as the promise of the outcome of a research study in the quality of life, social and economic incentives could expand the social network and amplify social support needed by individuals with PC or any deadly diseases. According to Kroenke et al. (2013), effective social support interventions need to evolve beyond social-emotional interventions and need to account for disease severity and treatment status.

References

Berkman, L. F., Glass, T., Brissette, I., & Seeman, T. E. (2000). From social integration to health: Durkheim in the new millennium. Social Science & Medicine51(6), 843-857. https://doi.org/10.1016/S0277-9536(00)00065-4

Christakis, N.A & Fowler, J.H. (2009). Connected: The Surprising Power of Our Social Networks and How They Shape Our Lives. (First ed.). New York: Little, Brown, and Company.

Christakis, N. A., & Fowler, J. H. (2013). Social contagion theory: examining dynamic social networks and human behavior. Statistics in medicine32(4), 556-577. doi: 10.1002/sim.5408

Diez-Roux, A. V. (1998). On genes, individuals, society, and epidemiology. American Journal of Epidemiology148(11), 1027-1032. http://dx.doi.org/10.1093/oxfordjournals.aje.a009578

Krieger, N. (2008). Proximal, Distal, and the Politics of Causation: What’s Level Got to Do With It?  American Journal of Public Health (AJPH), 98(2). http://dx.doi.org/10.2105/AJPH.2007.111278

Krieger, N. (2011). Epidemiology and the people’s health: theory and context (Vol. 213). New York: Oxford University Press.

Kroenke, C. H., Kwan, M. L., Neugut, A. I., Ergas, I. J., Wright, J. D., Caan, B. J., … & Kushi, L. H. (2013). Social networks, social support mechanisms, and quality of life after breast cancer diagnosis. Breast cancer research and treatment139(2), 515-527. doi:  10.1007/s10549-013-2477-2

Labilles, U. (2015a). Reevaluating the Impact of Cigarette Smoking on Pancreatic Cancer. Unpublished manuscript, College of Health Sciences, Public Health, Epidemiology, Walden University, Minneapolis.

Labilles, U. (2015b, September 27). A Promise to a Dying Brother [Web log post]. Retrieved from https://onenationsecho.com/2015/09/27/a-promised-to-a-dying-brother/.

Labilles, U. (2015c). Prospectus: Tobacco Use and Family Cancer History in the Pathopoiesis of Pancreatic Cancer. Unpublished manuscript, College of Health Sciences, Public Health, Epidemiology, Walden University, Minneapolis.

Labilles, U. (2016). The New Public Health: Beyond Genetics and Social Inequalities. Unpublished manuscript, College of Health Sciences, Public Health, Epidemiology, Walden University, Minneapolis.

Labilles, U. (2017). Pathopoiesis Mechanism of Smoking and Shared Genes in Pancreatic Cancer. ProQuest-CSA, LLC. Library of Congress, Copyright R# TX 8-490-984, Washington DC. doi: 10.13140/RG.2.2.30721.35681

Loomis, D., & Wing, S. (1990). Is molecular epidemiology a germ theory for the end of the twentieth century?. International journal of epidemiology, 19(1), 1-3. http://dx.doi.org/10.1093/ije/19.1.1

McEwen, B. S., & Getz, L. (2013). Lifetime experiences, the brain, and personalized medicine: An integrative perspective. Metabolism62, S20-S26. https://doi.org/10.1016/j.metabol.2012.08.020

Pearce, N. (1996). Traditional epidemiology, modern epidemiology, and public health. American journal of public health86(5), 678-683.

Rothermel, C. (2013). What is health economics and outcomes research? A primer for medical writers. AMWA Journal, 28(3)

Susser, M. (1985). Epidemiology in the United States after World War II: the evolution of technique. Epidemiologic reviews7(1), 147-177. http://dx.doi.org/10.1093/oxfordjournals.epirev.a036280

Travers, J., & Milgram, S. (1969). An experimental study of the small world problem. Sociometry, 425-443. doi: 10.2307/2786545

Verma, M., Khoury, M. J., & Ioannidis, J. P. (2013). Opportunities and challenges for selected emerging technologies in cancer epidemiology: mitochondrial, epigenomic, metabolomic, and telomerase profiling. Cancer Epidemiology Biomarkers & Prevention22(2), 189-200. http://dx.doi.org/10.1158/1055-9965.EPI-12-1263

Wemrell, M., Merlo, J., Mulinari, S., & Hornborg, A. C. (2016). Contemporary epidemiology: a review of critical discussions within the discipline and a call for further dialogue with social theory. Sociology Compass10(2), 153-171. doi: 10.1111/soc4.12345

 

From an Evolutionary Model to the Unified Paradigm of Cancer Causation (UPCC)

Screenshot (94)

Three essential events launched the field of cancer epidemiology during the 18th century. First, is Bernardino Ramazzini’s study on cervical cancer in 1713, the research of Percival Pott in 1775 that led the way on occupational carcinogenic exposure studies, and Thomas Venner on the danger of tobacco use in his Via Recta, published in London in 1620 (American Cancer Society, 2014). After two centuries when John Hill wrote a book entitled “Cautions Against the Immoderate Use of Snuff” in 1761; Krain (1970), along with other studies in the 1970s, Wynder, Mabuchi, Maruchi and Fortner (1973) explored the causality of tobacco use in the development of PC. Jones et al. (2008) found that PCs have an average of 63 genetic alterations that can explain the major features of pancreatic tumorigenesis. The intensive genetic studies described by Jones et al. (2008) gave way to the better understanding of the core set of pathways and processes, embracing the idea of Owens, Coffey, and Baylin (1982) that tumor heterogeneity is a fundamental facet of all solid tumors. While pancreatic cancer (PC) has few viable treatment options, Jones et al. (2008) suggested that the best hope for therapeutic development may lie in the discovery of agents that target the physiologic effects of the altered pathways and processes rather than their gene components. Above all, the significance that could not have been appreciated in the absence of global analysis is the identification of the precise genetic alterations that may be responsible for tumor pathway dysregulation (Jones et al., 2008).

The pathogenic theory of medicine or the germ theory of disease was highly controversial when first proposed as a concept that microorganisms are the cause of many diseases. After validation in the 19th century, germ theory revolutionized both medical thought and the art of surgery, becoming a fundamental part of modern medicine and clinical microbiology. My metatheory, the “Unified Paradigm of Cancer Causation (UPCC)” is as a composite of germ theory and Darwinian evolutionary system (Greaves & Maley, 2012) along with other theories will provide clarity on the narrative of the initiation of PC. Albeit the acceptance of the somatic mutation theory of carcinogenesis (SMT) as the mainstream narrative of how neoplasms develop (Soto & Sonnenschein, 2004), SMT included in the UPCC’s cocktail of theories will build on the arguments of the core principle of genetic variation and pattern of mutations (environmental and genetics) that are sufficient probable causes of the disease. UPCC could explain the behavior of PC cell in rationalizing the complex array of the possible interaction of smoking and inherited genes.

Pancreatic cancer is the fourth most prevalent cause of cancer death in Western societies and is projected to be the second leading cause within a decade (Waddell et al., 2015). While using the Darwinian methods that link human sociocultural progress to genetic evolution (Richerson & Boyd, 2000); Lynch and Rebbeck (2013) used a “Multi-level Biologic and Social Integrative Construct” (MBASIC) to integrate macro environment and individual factors with biology. Considering the limitation and information generated by single-level studies have reached a saturation point (Lynch & Rebbeck, 2013), I highlighted the significance of individual level (behaviors, carcinogenic exposures); and biologic level (inherited susceptibility variants in my dissertation “Pathopoiesis Mechanism of Smoking and Shared Genes in Pancreatic Cancer.” Germline changes associated with PC could range from slightly increased risk (low penetrance genes) to high lifetime risk (high penetrance genes). Given that PC is the antecedent of inherited (germline), and acquired (somatic) mutations in cancer-causing genes, adding the probable correlation between gender and age, modifiable risk factors to the equation that could trigger or wake up a sleeping germline mutation could position the result of a study for improved public health intervention, translation, and implementation in clinical settings to alter the expression of the disease.

References

American Cancer Society. (2014). History of cancer epidemiology. Retrieved from http://www.cancer.org/cancer/cancerbasics/thehistoryofcancer/the-history-of-cancer-cancer-epidemiology

Greaves, M., & Maley, C. C. (2012). Clonal evolution in cancer. Nature, 481(7381), 306-313. doi: 10.1038/nature10762

Hill, J. (1761). Cautions Against the Immoderate Use of Snuff: Founded on the Known Qualities of the Tobacco Plant and the Effects It Must Produce When This Way Taken into the Body. R. Baldwin and J. Jackson, London, UK. (Held now only as a self-contained pamphlet at shelfmark 1560/2918 in the British Library).

Jones, S., Hruban, R. H., Kamiyama, M., Borges, M., Zhang, X., Parsons, D. W., … & Iacobuzio-Donahue, C. A. (2009). Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene. Science324(5924), 217-217. doi: 10.1126/science.1171202

Krain, L. S. (1970). The rising incidence of carcinoma of the pancreas—real or apparent?. Journal of surgical oncology2(2), 115-124. doi: 10.1002/jso.2930020206

Labilles, U. (2015a). Reevaluating the Impact of Cigarette Smoking on Pancreatic Cancer. Unpublished manuscript, College of Health Sciences, Public Health, Epidemiology, Walden University, Minneapolis.

Labilles, U. (2015b, September 27). A Promise to a Dying Brother [Web log post]. Retrieved from https://onenationsecho.com/2015/09/27/a-promised-to-a-dying-brother/.

Labilles, U. (2015c). Prospectus: Tobacco Use and Family Cancer History in the Pathopoiesis of Pancreatic Cancer. Unpublished manuscript, College of Health Sciences, Public Health, Epidemiology, Walden University, Minneapolis.

Labilles, U. (2016). The New Public Health: Beyond Genetics and Social Inequalities. Unpublished manuscript, College of Health Sciences, Public Health, Epidemiology, Walden University, Minneapolis.

Labilles, U. (2017). Pathopoiesis Mechanism of Smoking and Shared Genes in Pancreatic Cancer. ProQuest-CSA, LLC. Library of Congress, Copyright R# TX 8-490-984, Washington DC. doi: 10.13140/RG.2.2.30721.35681

Lynch, S. M., & Rebbeck, T. R. (2013). Bridging the gap between biologic, individual, and macroenvironmental factors in cancer: a multilevel approach. Cancer Epidemiology Biomarkers & Prevention22(4), 485-495. doi: 10.1158/1055-9965.EPI-13-0010

Owens, A.H., Coffey, D.S. & Baylin, S.B. (1982). Tumor cell heterogeneity: Origins and Implications. (Vol 4). San Diego: Academic Press.

Richerson, P. J., & Boyd, R. (2000). Evolution: The Darwinian theory of social change: an homage to Donald T. Campbell. Paradigms of Social Change: Modernization, Development, Transformation, Evolution, pp. 1-30. http://www.des.ucdavis.edu/faculty/richerson/evolutionberlin.pdf

Richerson, P. J., Boyd, R., & Henrich, J. (2010). Gene-culture coevolution in the age of genomics. Proceedings of the National Academy of Sciences, 107(Supplement 2), 8985-8992. doi: 10.1073/pnas.0914631107

Soto, A. M., & Sonnenschein, C. (2004). The somatic mutation theory of cancer: growing problems with the paradigm?. Bioessays26(10), 1097-1107. doi: 10.1002/bies.20087

Waddell, N., Pajic, M., Patch, A. M., Chang, D. K., Kassahn, K. S., Bailey, P., … & Quinn, M. C. (2015). Whole genomes redefine the mutational landscape of pancreatic cancer. Nature518(7540), 495-501. doi: 10.1038/nature14169

Wynder, E. L., Mabuchi, K., Maruchi, N., & Fortner, J. G. (1973). Epidemiology of cancer of the pancreas. Journal of the National Cancer Institute50(3), 645-667. https://doi.org/10.1093/jnci/50.3.645

 

Continuing the Journey to Make a Difference

Innovative Management and Development (Inno MD) from Uly Labilles, DMD, Ph.D on Vimeo.