Informed Consent in Cross-cultural Perspective: Clinical Research in the Tibetan Autonomous Region, PRC

Procedures of Informed Consent are considered a high priority for international biomedical research. However, informed consent protocols are not necessarily transferable across cultural, national or ethnic groups. Recent debates identify the need for balancing ethical universals with practical and local conditions and paying attention to questions of cultural competence when it comes to the Informed Consent process for clinical biomedical research. This article reports on the results of a two-year effort to establish a culturally appropriate Informed Consent process for biomedical research in the Tibet Autonomous Region in the People's Republic of China. A team of Tibetan and American researchers, physicians, health professionals and medical anthropologists conducted the research. The Informed Consent was specifically for undertaking a triple-blind, double placebo-controlled randomized clinical trial of a Tibetan medicine compared with Misoprostol for reducing postpartum blood loss. The findings suggest greater need for flexibility and cooperation in establishing Informed Consent protocols across cultures and nations.     

Artificial womb technology and clinical translation: Innovative treatment or medical research?

In 2017 and 2019, two research teams claimed ‘proof of principle’ for artificial womb technology (AWT). AWT has long been a subject of speculation in bioethical literature, with broad consensus that it is a welcome development. Despite this, little attention is afforded to more immediate ethical problems in the development of AWT, particularly as an alternative to neonatal intensive care. To start this conversation, I consider whether experimental AWT is innovative treatment or medical research. The research–treatment distinction, pervasive in regulation worldwide, is intended to isolate research activities and subject them to a greater degree of oversight. I argue that there is a tendency in the literature to conceptualize AWT for partial ectogenesis as innovative treatment. However, there are sufficiently serious ethical concerns with experimental AWT that mean that it must not be first used on humans on the basis that it is a ‘beneficial treatment’. First, I outline the prospects for translation of AWT animal studies into treatment for human preterms. Second, I challenge the conceptualizations of experimental AWT as innovative treatment. It must be considered medical research to reflect the investigatory nature of the process and guarantee sufficient protections for subjects. Identifying that AWT is research is crucial in formulating further ethico-legal questions regarding the experimental use of AWT. Third, I demonstrate that clinical trials will be a necessary part of the clinical translation of AWT because of requirements laid out by regulators. I consider the justification for clinical trials and highlight some of the crucial ethical questions about the conditions under which they should proceed.     

Ethical and legal aspects of oncogenomics

The discovery of the genes and cellular pathways that play fundamental roles in several diseases, and the understanding of many diseases at a molecular level due to the advances in the field of genomics, have revolutionized the diagnosis, therapy and prevention of human diseases. Application of genetic testing in numerous medical fields, including pharmacogenomics and oncogenomics, raised numerous ethical questions and introduced legal instruments that are aimed at ensuring the appropriate protection of human research participants. For the effective development of human genomics and translation of novel, validated biomarkers into potentially useful clinical applications in personalized medicine, there is a need for clear ethical standards and principles in all phases of clinical research.     

Are Phase 1 Trials Therapeutic? Risk,Ethics, and Division of Labor

Despite their crucial role in the translation of pre‐clinical research into new clinical applications, phase 1 trials involving patients continue to prompt ethical debate. At the heart of the controversy is the question of whether risks of administering experimental drugs are therapeutically justified. We suggest that prior attempts to address this question have been muddled, in part because it cannot be answered adequately without first attending to the way labor is divided in managing risk in clinical trials. In what follows, we approach the question of therapeutic justification for phase 1 trials from the viewpoint of five different stakeholders: the drug regulatory authority, the IRB, the clinical investigator, the referring physician, and the patient. Our analysis shows that the question of therapeutic justification actually raises multiple questions corresponding to the roles and responsibilities of the different stakeholders involved. By attending to these contextual differences, we provide more coherent guidance for the ethical negotiation of risk in phase 1 trials involving patients. We close by discussing the implications of our argument for various perennial controversies in phase 1 trial practice.     

Bioethics for clinicians: 16. Dealing with demands for inappropriate treatment

Demands by Patients or their Families for treatment thought to be inappropriate by health care providers constitute an important set of moral problems in clinical practice. A variety of approaches to such cases have been described in the literature, including medical futility, standard of care and negotiation. Medical futility fails because it confounds morally distinct cases: demand for an ineffective treatment and demand for an effective treatment that supports a controversial end (e.g., permanent unconsciousness). Medical futility is not necessary in the first case and is harmful in the second. Ineffective treatment falls outside the standard of care, and thus health care workers have no obligation to provide it. Demands for treatment that supports controversial ends are difficult cases best addressed through open communication, negotiation and the use of conflict-resolution techniques. Institutions should ensure that fair and unambiguous procedures for dealing with such cases are laid out in policy statements.     

Radiomics in radiooncology – Challenging the medical physicist

PurposeNoticing the fast growing translation of artificial intelligence (AI) technologies to medical image analysis this paper emphasizes the future role of the medical physicist in this evolving field. Specific challenges are addressed when implementing big data concepts with high-throughput image data processing like radiomics and machine learning in a radiooncology environment to support clinical decisions.MethodsBased on the experience of our interdisciplinary radiomics working group, techniques for processing minable data, extracting radiomics features and associating this information with clinical, physical and biological data for the development of prediction models are described. A special emphasis was placed on the potential clinical significance of such an approach.ResultsClinical studies demonstrate the role of radiomics analysis as an additional independent source of information with the potential to influence the radiooncology practice, i.e. to predict patient prognosis, treatment response and underlying genetic changes. Extending the radiomics approach to integrate imaging, clinical, genetic and dosimetric data (‘panomics’) challenges the medical physicist as member of the radiooncology team.ConclusionsThe new field of big data processing in radiooncology offers opportunities to support clinical decisions, to improve predicting treatment outcome and to stimulate fundamental research on radiation response both of tumor and normal tissue. The integration of physical data (e.g. treatment planning, dosimetric, image guidance data) demands an involvement of the medical physicist in the radiomics approach of radiooncology. To cope with this challenge national and international organizations for medical physics should organize more training opportunities in artificial intelligence technologies in radiooncology.     

Prospects for translational regenerative medicine

Translational medicine is an evolutional concept that encompasses the rapid translation of basic research for use in clinical disease diagnosis, prevention and treatment. It follows the idea "from bench to bedside and back", and hence relies on cooperation between laboratory research and clinical care. In the past decade, translational medicine has received unprecedented attention from scientists and clinicians and its fundamental principles have penetrated throughout biomedicine, offering a sign post that guides modern medical research toward a patient-centered focus. Translational regenerative medicine is still in its infancy, and significant basic research investment has not yet achieved satisfactory clinical outcomes for patients. In particular, there are many challenges associated with the use of cell- and tissue-based products for clinical therapies. This review summarizes the transformation and global progress in translational medicine over the past decade. The current obstacles and opportunities in translational regenerative medicine are outlined in the context of stem cell therapy and tissue engineering for the safe and effective regeneration of functional tissue. This review highlights the requirement for multi-disciplinary and inter-disciplinary cooperation to ensure the development of the best possible regenerative therapies within the shortest timeframe possible for the greatest patient benefit.     

Tibetan medicine plurality

Tibetan medicine historically has had multiple medical lineages, despite ancient, shared literary medical canons. However, since the second half of the 20th century in Tibet, increasing state control and commoditization has lead to centralization and standardization of Tibetan medicine. Here we investigate how much variation in the use of medicinal plants remains in contemporary Tibetan medicine. Medicinal plants used and/or sold by fifteen Tibetan medical institutions, markets, and doctors, as well as two additional non-Tibetan markets, are inventoried and vouchered (where allowed). The data are ordered by Non-metric Multidimensional Scaling. Four distinct groups are defined: (1) government recognized Tibetan medical institutions and their disciples both in Lhasa and elsewhere, (2) local herbal doctors near Mt. Khawa Karpo, eastern Himalayas, (3) Tibetan medicinal markets in Lhasa and near Mt. Khawa Karpo, and (4) non-Tibetan medicinal markets near Dali and Kunming, Yunnan. This clearly documents the plurality of Tibetan medical traditions—official, local, and market—while differentiating these from non-Tibetan markets.     

Ethical hurdles for translational research

The notion of translational research has gained considerable currency over the past few years. While such an approach promises great scientific and clinical advances, the penumbra of translational research tends to incorporate prioritizing scientific projects based upon their potential for translation; tight financial connections between sponsors, scientists and clinical investigators; and sometimes research involving biological approaches for which there is little experience determining safety. It is these aspects of translational research that raise some serious ethical challenges. In this report, we examine three specific areas that raise ethical questions: (1) the potential implications of prioritizing research objectives based on the potential for translation; (2) cautions related to moving from bench to bedside (and back again); and (3) unique questions for translational research initiatives in academic medical centers. Based on this examination, it is clear that the financial and ethical costs as well as benefits of taking a translational approach need to be considered. In the meantime, exquisite attention needs to be paid whenever translational research is likely to affect the traditional fiduciary responsibilities of scientists, clinicians and institutions to research subjects, patients and students. Successful mechanisms that might be developed to address any untoward effects should be shared and evaluated.     

Improving the care of people with traumatic brain injury through the Neurotrauma Evidence Translation (NET) program: protocol for a program of research

ABSTRACT: The Neurotrauma Evidence Translation (NET) program was funded in 2009 to increase the uptake of research evidence in the clinical care of patients who have sustained traumatic brain injury. This paper reports the rationale and plan for this five-year knowledge translation research program. The overarching aims of the program are threefold: to improve outcomes for people with traumatic brain injury; to create a network of neurotrauma clinicians and researchers with expertise in knowledge translation and evidence-based practice; and to contribute knowledge to the field of knowledge translation research. The program comprises a series of interlinked projects spanning varying clinical environments and disciplines relevant to neurotrauma, anchored within four themes representing core knowledge translation activities: reviewing research evidence; understanding practice; developing and testing interventions for practice change; and building capacity for knowledge translation in neurotrauma. The program uses a range of different methods and study designs, including: an evidence fellowship program; conduct of and training in systematic reviews; mixed method study designs to describe and understand factors that influence current practices (e.g., semistructured interviews and surveys); theory-based methods to develop targeted interventions aiming to change practice; a cluster randomised trial to test the effectiveness of a targeted theory-informed intervention; stakeholder involvement activities; and knowledge translation events such as consensus conferences.     

Suffering the Winds of Lhasa: Politicized Bodies, Human Rights, Cultural Difference, and Humanism in Tibet

Tibetan refugees and Western activists note that if universal human rights standards were enforced in China, Tibetans would suffer less and come closer to political independence. This article explores potential problems of universalism and individualism in human rights discourse by examining understandings of the body and suffering among Lhasa Tibetan women. Data are taken from accounts of political prisoners and women patients at Lhasa's traditional Tibetan medical hospital. The data suggest a collective subjectivity, based on ideas about karma and congruencies of body, mind, and society that contrast with those found in international human rights discourse. Tibetans are forced to adopt universalist and individualist positions to make their claims for human rights heard while ironically articulating ideas about suffering that would contest such universalist positions. The article proposes a need for alternative conceptualizations of human rights taken from Tibetan epistemologies of suffering, and illustrates the utility of medical anthropological inquiries about embodiment and subjectivity for addressing larger political debates about human rights. [Traditional Tibetan Medicine, Human Rights, Epistemology, Bodily Suffering]     

Clinical practice vs. state-of-the-art research and future visions: Report on the 4D treatment planning workshop for particle therapy – Edition 2018 and 2019

The 4D Treatment Planning Workshop for Particle Therapy, a workshop dedicated to the treatment of moving targets with scanned particle beams, started in 2009 and since then has been organized annually. The mission of the workshop is to create an informal ground for clinical medical physicists, medical physics researchers and medical doctors interested in the development of the 4D technology, protocols and their translation into clinical practice. The 10th and 11th editions of the workshop took place in Sapporo, Japan in 2018 and Krakow, Poland in 2019, respectively.This review report from the Sapporo and Krakow workshops is structured in two parts, according to the workshop programs. The first part comprises clinicians and physicists review of the status of 4D clinical implementations. Corresponding talks were given by speakers from five centers around the world: Maastro Clinic (The Netherlands), University Medical Center Groningen (The Netherlands), MD Anderson Cancer Center (United States), University of Pennsylvania (United States) and The Proton Beam Therapy Center of Hokkaido University Hospital (Japan). The second part is dedicated to novelties in 4D research, i.e. motion modelling, artificial intelligence and new technologies which are currently being investigated in the radiotherapy field.     

Comparing Conservation Priorities for Useful Plants Among Botanists and Tibetan Doctors

Perspectives of diverse constituencies need to be incorporated when developing conservation strategies. In Menri (Medicine Mountains) of the Eastern Himalayas, Tibetan doctors and professional botanists were interviewed about conservation of useful plants. We compare these two perspectives and find they differ significantly in conservation priorities (Wilcoxon Signed Ranks P < 0.05), both in how they prioritized, as well as the priorities themselves. Tibetan doctors first consider which plants are most important to their medical practice and, then secondarily, the conservation status of these plants. Additionally, perceptions of threatened medicinal plants differ among Tibetan doctors who received medical training in Lhasa, who were local trained, and who were self-taught. In contrast, professional botanists came to a consensus among themselves by first considering the conservation status of plants and then considering use. We conclude that, in order to effect community based conservation, opinions from both Tibetan doctors and professional botanists should be considered in establishing conservation priorities and sustainable conservation programs. Furthermore, we set our own research agenda based on combined perspectives.     

Perspectives on an Education in Computational Biology and Medicine

The mainstream application of massively parallel, high-throughput assays in biomedical research has created a demand for scientists educated in Computational Biology and Bioinformatics (CBB). In response, formalized graduate programs have rapidly evolved over the past decade. Concurrently, there is increasing need for clinicians trained to oversee the responsible translation of CBB research into clinical tools. Physician-scientists with dedicated CBB training can facilitate such translation, positioning themselves at the intersection between computational biomedical research and medicine. This perspective explores key elements of the educational path to such a position, specifically addressing: 1) evolving perceptions of the role of the computational biologist and the impact on training and career opportunities; 2) challenges in and strategies for obtaining the core skill set required of a biomedical researcher in a computational world; and 3) how the combination of CBB with medical training provides a logical foundation for a career in academic medicine and/or biomedical research.     

Unpredictability of vigilance in two sympatric Tibetan ungulates

Vigilance is important for anti-predation, and different animals adopt different vigilance strategies. Instantaneous and sequential randomness in vigilance behavior are two main principles for the classic Pulliam model (1973). Given this context, we studied the vigilance behaviors in two wild cloven-hoofed animals, the Tibetan antelope (Pantholops hodgsonii) and the Tibetan gazelle (Procapra picticaudata) on Qinghai–Tibet Plateau, to explore if the two randomness principles work across species. The results showed that the distribution of inter-scan intervals of both Tibetan antelope and Tibetan gazelle followed the negative exponential distribution; inter-scans of both Tibetan antelope and Tibetan gazelle were unrelated with their previous scan, and most sequences of inter-scan intervals could be considered as random organized or unpredictable. In conclusion, the vigilance patterns of Tibetan antelope and Tibetan gazelle followed instantaneous randomness and sequential randomness of Pulliam model. A random vigilance strategy might be the best choice for Tibetan ungulates, and how to distinguish the social vigilance from anti-predator vigilance is an important issue for future research.     

Age and the Metabolic Syndrome as Risk Factors for Ischemic Stroke: Improving Preclinical Models of Ischemic Stroke

Ischemic stroke represents a leading cause of morbidity and mortality in the developed world. This disabling and sometimes fatal event puts an ever increasing burden on the family members and medical professionals who care for stroke victims. Preclinical ischemic stroke research has predominantly utilized young adult, healthy animals, a clear discrepancy when considering the clinical population affected by stroke. A broad spectrum of risk factors such as age, obesity, diabetes, and hypertension has been associated with an increased stroke risk. The effect of these comorbidities on both stroke pathophysiology and outcome has not been emphasized and has been recognized as a shortcoming of preclinical studies. By addressing these conditions in experimental models of ischemic stroke, it may be possible to more accurately represent the clinical scenario and improve therapeutic translation from bench-to-bedside. In this work, we review many of the risk factors associated with increased stroke risk, particularly as each risk factor relates to inflammation. Additionally, we explore potential animal models that could be utilized in identifying the contribution of these risk factors to stroke outcome. By investigating the risk factors for stroke and how these may alter stroke pathophysiology, the present discrepancies between preclinical studies and the clinical reality can be reconciled in an effort to improve therapeutic development and translation from bench-to-bedside.     

藏族生物人类学研究回顾

藏族生活在具有世界屋脊之称的青藏高原,特殊的生态环境和特殊的文化背景造就了藏族特殊的适应高原缺氧机制和体质特征,引起了国内外学者的广泛关注和浓厚的研究兴趣。本文从国内外数据库收集了492篇国内外杂志发表的关于藏族人类学研究方面的论文。通过统计、分析并结合我们的工作,初步回顾了30年藏族人类学研究,重点分析了藏族与汉族的族源关系。这些文献显示,从体质特征、血型、分子生物学和考古材料等方面都证明藏族是中华民族大家庭中不可缺少的的一员。本文最后展望了藏族生物人类学今后的发展。     

Application of a nonradioactive method of measuring protein synthesis in industrially relevant chinese hamster ovary cells

Due to the high medical and commercial value of recombinant proteins for clinical and diagnostic purposes, the protein synthesis machinery of mammalian host cells is the subject of extensive research by the biopharmaceutical industry. RNA translation and protein synthesis are steps that may determine the extent of growth and productivity of host cells. To address the problems of utilization of current radioisotope methods with proprietary media, we have focused on the application of an alternative method of measuring protein synthesis in recombinant Chinese hamster ovary (CHO) cells. This method employs puromycin as a nonradioactive label which incorporates into nascent polypeptide chains and is detectable by western blotting. This method, which is referred to as SUnSET, successfully demonstrated the expected changes in protein synthesis in conditions that inhibit and restore translation activity and was reproducibly quantifiable. The study of the effects of feed and sodium butyrate addition on protein synthesis by SUnSET revealed an increase following 1 h feed supplementation while a high concentration of sodium butyrate was able to decrease translation during the same treatment period. Finally, SUnSET was used to compare protein synthesis activity during batch culture of the CHO cell line in relation to growth. The results indicate that as the cells approached the end of batch culture, the global rate of protein synthesis declined in parallel with the decreasing growth rate. In conclusion, this method can be used as a “snapshot” to directly monitor the effects of different culture conditions and treatments on translation in recombinant host cells. © 2013 American Institute of Chemical Engineers Biotechnol. Prog., 29:1043–1049, 2013     

Discovery and Validation of Clinical Biomarkers of Cancer: A Review Combining Metabolomics and Proteomics

Early detection and diagnosis of cancer can allow timely medical intervention, which greatly improves chances of survival and enhances quality of life. Biomarkers play an important role in assisting clinicians and health care providers in cancer diagnosis and treatment follow‐up. In spite of years of research and the discovery of thousands of candidate cancer biomarkers, only a few have transitioned to routine usage in the clinic. This review highlights advances in proteomics technologies that have enabled high rates of discovery of candidate cancer biomarkers and evaluates integration with other omics technologies to improve their progress through to validation and clinical translation. Furthermore, it gauges the role of metabolomics technology in cancer biomarker research and assesses it as a complementary tool in aiding cancer biomarker discovery and validation.     

An international basic science and clinical research summer program for medical students

An important part of training the next generation of physicians is ensuring that they are exposed to the integral role that research plays in improving medical treatment. However, medical students often do not have sufficient time to be trained to carry out any projects in biomedical and clinical research. Many medical students also fail to understand and grasp translational research as an important concept today. In addition, since medical training is often an international affair whereby a medical student/resident/fellow will likely train in many different countries during his/her early training years, it is important to provide a learning environment whereby a young medical student experiences the unique challenges and value of an international educational experience. This article describes a program that bridges the gap between the basic and clinical research concepts in a unique international educational experience. After completing two semester curricula at Alfaisal University in Riyadh, Kingdom of Saudi Arabia, six medical students undertook a summer program at St. Boniface Hospital Research Centre, in Winnipeg, MB, Canada. The program lasted for 2 mo and addressed advanced training in basic science research topics in medicine such as cell isolation, functional assessment, and molecular techniques of analysis and manipulation as well as sessions on the conduct of clinical research trials, ethics, and intellectual property management. Programs such as these are essential to provide a base from which medical students can decide if research is an attractive career choice for them during their clinical practice in subsequent years. An innovative international summer research course for medical students is necessary to cater to the needs of the medical students in the 21st century.